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Metastatic Prostate Cancer—A Review of Current Treatment Options and Promising New Approaches

Philip posdzich.

1 Department of Urology, University Hospital Essen, 45147 Essen, Germany

Christopher Darr

Thomas hilser.

2 Department of Internal Medicine (Oncology), University Hospital Essen, 45147 Essen, Germany

Ken Herrmann

3 Department of Nuclear Medicine, University Hospital Essen, 45147 Essen, Germany

Boris Hadaschik

Viktor grünwald, simple summary.

Prostate cancer is the most common tumor in men. Although there have been many new developments in the last few years, metastatic castration resistant prostate cancer remains a deadly disease. This article provides an overview of currently approved treatment options as well as new therapies that are not standard of care yet. All relevant developments from classical androgen deprivation therapy (ADT) to bispecific T-cell engagers (BiTE) are considered.

Androgen deprivation therapy (ADT) alone has been the standard of care for many years in men with metastatic prostate cancer. Due to the limited survival under this monotherapy, many new treatment options have been developed in the last few years. Regarding hormone-sensitive prostate cancer, combination therapies of two or three agents of ADT, androgen receptor signaling inhibitors (ARSI) and chemotherapy have been established and led to a significant benefit in overall survival. Additionally, in patients with metastatic castration-resistant prostate cancer, there are many new therapeutic approaches. Chemotherapy alone has been the standard of care in this situation. In the last years, some new therapeutic options have been developed, which led to an improved survival after progression under chemotherapy. These therapies include ARSI, PARP inhibitors and Lu-PSMA radioligand therapy. The use of a bispecific T-cell engager (BiTE) in this setting is a new promising therapeutic approach, which has not been established as standard of care yet. The role of immunotherapy in prostate cancer is still under investigation. Overall, many new treatment options make prostate cancer therapy a challenging and promising field.

1. Introduction

Prostate cancer is the most common solid cancer in men worldwide. The number of estimated new prostate cancers in the US in 2022 was 268,490. The number of estimated deaths due to prostate cancer is 34,500 [ 1 ]. Surgery and radiotherapy are the mainstay of treatment in localized disease. Androgen-deprivation-therapy (ADT), androgen signaling inhibition (ARSI) and chemotherapy dominate the standard medical treatment in recurrent or metastatic disease. However, the majority of patients acquire castration-resistance, which is associated with a poor prognosis.

The latest advancements in systemic treatments were the addition of Poly ADP-Ribose Polymerase Inhibitor (PARPi) and radio-ligand therapies (RLT) to the armentarium. While check point inhibitors (CPI) have revolutionized anti-cancer treatment in many diseases they were less successful in prostate cancer. A major driver of this immune resistance is derived from the dominance of a non-inflamed “cold” tumor environment in prostate cancer [ 2 ]. However, some activity has been noted for ipilimumab in men with mCRPC who were treated with at least one chemotherapy and had evidence of progression after the discontinuation of ADT [ 3 ], as well as for pembrolizumab in a subgroup of genetically instable prostate cancer patients [ 4 ].

Novel concepts are needed to advance immunotherapies in prostate cancer. Sipuleucel-T indicated that T-cell-based therapies were clinically active in principle and have led to further clinical development. Bispecific T Cell engager is a novel promising anti-cancer treatment modality in non-inflamed cancers, such as prostate cancer. These compounds re-direct T-cells to the tumor environment by targeting a cancer-specific epitope, such as PSMA in prostate cancer, which is linked to a component of the T-cell receptor (TCR). This mechanism recruits T-cells to the tumor milieu by binding to prostate cancer cells, which activates T-cells and enables immunologic anti-tumor response. In this article, we will give an overview of the current therapy standard in mHSPC and mCRPC, and introduce bispecific T-cell-engager as a new mechanism of action to overcome immune resistance.

A review of the Medline database through PubMed was conducted to identify pivotal trials of approved and contemporary medical treatments in prostate cancer. Guideline-recommended regimens were selected and the current EAU Guideline on prostate cancer served as a reference.

3. Current Treatment Options in Metastatic Prostate Cancer

3.1. metastatic hormone-sensitive prostate cancer (mhspc), 3.1.1. prognostic factors.

Several criteria have been established to estimate the prognosis of metastatic hormone-sensitive prostate cancer. Most common criteria are CHAARTED and LATITUDE criteria. These are summarized in Table 1 and Table 2 .

CHAARTED criteria [ 5 ].

LATITUDE Criteria [ 6 ].

The occurrence of “de novo” metastatic hormone-sensitive disease at the time of initial diagnosis was identified as a poor prognostic factor. The median overall survival (OS) was 51.6 months in low volume disease (HR = 1.64; 95% CI 1.16–2.31) and 43.2 months in high volume disease (HR = 2.48, 95% CI 1.83–3.36) compared to the reference group (prior local treatment/low volume disease HR = 1). These results differed substantially from those patients who had local therapy prior to the diagnosis of metastatic disease, i.e., metachronous metastatic prostate cancer. In this population, OS in low volume disease was 92.4 months (HR = 1) and 55.2 months in high volume disease (HR = 1.9, 95% CI 1.31–2.75 [ 7 ].

ADT is the standard treatment approach in mHSPC patients and may consist of Luteinizing hormone-releasing hormone (LHRH) agonists, LHRH antagonists or bilateral orchiectomy. In previous decades, ADT resided as single modality, but this is not the standard of care (SOC) anymore. OS in mHSPC patients treated with ADT alone is about 42 months [ 8 ].

Today, therapies that combine ADT with ARSI, chemotherapy, or both, yielded superior OS results. Single agent ADT has limited value and remains an option in elderly, frail patients, only.

3.1.3. Combination Therapies

The advent of combination therapies has intensified medical treatment and improved OS prognosis in prostate cancer patients with mHSPC. Different components were added to the ADT backbone.

An early set of treatment intensification trials tested the combination of ADT + docetaxel. There were two important trials, which investigated the combination of ADT and Docetaxel.

The STAMPEDE trial included patients with newly diagnosed M1 or N+ disease, locally advanced disease (cT3, cT4, ISUP grade at least 4, PSA at least 40 ng/mL) and patients with relapse after local treatment (PSA at least 4 ng/mL or PSA doubling time under 6 months or PSA level over 20 ng/mL, M or N relapse). In all, 689/724 (95%) of patients in the control arm and 347/362 patients in the Docetaxel arm had no previous treatment. A total of 1184 patients received the standard of care (ADT) and 592 patients received ADT + docetaxel. The median OS in the ADT group was 43.1 months, the estimated 5-year OS was 37% (CI 34–41%). In contrast, the median OS in patients who received ADT + Docetaxel was 59.1 months, the estimated 5-year OS was 49% ( p = 0.003, HR = 0.81, 95% CI 0.69–0.95) [ 9 ].

The second Important trial was called CHAARTED, which also investigated the impact of ADT + docetaxel in patients with mHSPC and ECOG performance score 0–2. A distinction was made between high volume and low volume disease. In the overall patient population, OS was 57.6 months in the ADT + docetaxel group in contrast to 47.2 months in the ADT alone group (HR = 0.72, 95% CI 0.59 to 0.89; p = 0.0018). Subgroups of patients with high and low volume disease achieved different treatment effects. While ADT + docetaxel vs. ADT achieved a superior OS of 51.2 vs. 34.4 months (HR = 0.63, 95% CI 0.50 to 0.79; p < 0.001) in high volume disease, there was no benefit in patients with low volume disease in longterm follow-up (HR = 1.04, 95% CI 0.70 to 1.55; p = 0.86) [ 10 ].

As a result, OS in newly diagnosed metastatic hormone-sensitive prostate cancer is superior for ADT + docetaxel than ADT alone, but that effect of chemotherapy is restricted to high volume disease only.

3.1.4. ADT + Androgen Receptor Signaling Inhibitors (ARSI)

Abiraterone acetate: selective inhibitor of steroid 17α-hydroxylase (cyp17a1).

In this section, we will discuss the impact of three different androgen receptor signaling inhibitors in addition to ADT.

The STAMPEDE trial also investigated the impact of Abiraterone Acetate (AA), a selective inhibitor of the enzyme steroid 17α-hydroxylase (CYP17A1) and prednisone in addition to ADT. Inclusion criteria were already mentioned above. In all, 957 received ADT alone, 960 patients were treated with ADT and Abiratrone Acetate + prednisone (AAP). There was a significant benefit in OS (HR = 0.63, 95% CI 0.52 to 0.76; p < 0.001) in patients who received the combination therapy which corresponded to 3-year OS rates 83% vs. 76%. Metastatic status at time of randomization had no significant impact on treatment effect ( p = 0.37) [ 11 ].

In the LATITUDE trial, ADT + Placebo ( n = 597 pts.) was compared to ADT + AAP ( n = 602 pts.). Only patients with high-risk newly diagnosed metastatic disease, ISUP grade > 4, at least three bone lesions or measurable visceral metastases were included. The combination of ADT + AAP reported significant OS improvement (HR = 0.62, 95% CI 0.51–0.76; p < 0.001) when compared to ADT alone. Three year OS rates were: 66% in ADT + AAP vs. 49% in ADT + Placebo group [ 6 ].

In summary, the combination therapy of ADT + AAP provided a significant survival benefit over ADT monotherapy.

Enzalutamide: A Competitive Androgen Receptor Blocker

The ENZAMET trial included mHSPC patients (with distant metastases (M1) and ECOG score 0–2). 1125 men (588 with high volume disease, 537 with low volume disease) were 1:1 randomized to receive enzalutamide + ADT or ADT + standard nonsteroidal antiandrogen drug (bicalutamide, nilutamide, flutamide). Overall survival favored ADT + enzalutamide (HR = 0.67, 95% CI 0.52–0.86; p = 0.002) and 3 year OS rate were 80% in the Enzalutamide group and 72% for ADT alone. Regarding the volume of disease, the proportion alive after 36 months was 0.82 (0.75 to 0.87) in the control group vs. 0.90 (0.84 to 0.93) in the Enzalutamide group and low volume disease. In high volume disease, proportion alive after 36 months was 0.64 (0.58 to 0.70) in the control group and 0.71 (0.64 to 0.76) in the Enzalutamide group. There was no statistically significant impact of volume of disease ( p = 0.14) [ 12 ].

Apalutamide: Inhibitor of the Ligand-Binding Domain of the Androgen Receptor

In the TITAN study, apalutamide + ADT ( n = 525) was compared to ADT + Placebo ( n = 527) in patients with mHSPC. A total of 94 of 525 patients in the Apalutamide group and 79 of 527 in the placebo group had previous treatment for localized disease. The other patients were de novo metastasized. The study reported superior OS in favor for the combination arm (HR = 0.67, 95% CI 0.51–0.89; p = 0.005). After 24 months, there was an overall survival of 82.4% in the Apalutamide group, but only 73.5% OS in the Placebo group [ 13 ] In the final analysis after 405 deaths, it was shown that apalutamide decreased the risk of death by 35% (HR = 0.65; 95% CI, 0.53 to 0.79; p < 0.0001) [ 14 ].

The results of these trials indicated that the combination therapy of ADT and ARSI improved OS in mHSPC patients than ADT alone. Both patient groups, high volume disease and low volume disease had a benefit from combination therapy.

3.1.5. Triple Combinations (ADT + ARSI + Docetaxel)

In this section, triple combinations in the treatment of mHSPC will be discussed.

Darolutamide is a competitive androgen receptor inhibitor and reported improved metastasis free survival and overall survival in non-metastatic CRPC patients. The principal activity paved the way for further testing in an earlier setting. The ARASENS trial investigated the combination of darolutamide + ADT + docetaxel ( n = 651) compared to placebo + ADT + docetaxel ( n = 655). The primary analysis at first data cut-off showed that the risk of death was reduced by 32.5% in the triple-therapy arm when compared to the ADT + docetaxel doublet [ 15 ].

PEACE-1 is a complex study and consisted of four arms. At this point, only the combination therapy of ADT + docetaxel with or without abiraterone acetate and prednisone (AAP) were considered for analyses. The median rPFS was prolonged by 2.5 years in patients who received the AAP containing triplet (HR = 0.5, 95% CI 0.40–0.62; p < 0.0001). Furthermore, there was a 25% reduction in the risk of death in patients who received the triplet (HR = 0.75, 95% CI 0.59–0.95); p = 0.017). The addition of Abiraterone improved the median OS from 4.72 years (SOC) to 5.72 years (SOC+abiraterone) (HR = 0.82, 95% CI 0.69–0.98; p = 0.030). Regarding patients with high tumor volume, there was a median survival benefit of 1.5 years in patients who were treated with the triplet (HR = 0.72, 95% CI 0.55–0.95; p = 0.019) [ 16 ].

As a result, triple therapies show a promising survival benefit in mHSPC patients, especially in those with high tumor burden. There are no comparisons between the triple and ADT + ARSI doublets available.

Table 3 provides a summary of the mentioned treatment options in mHSPC:

List of treatment options and survival rates in mHSPC.

3.2. Metastatic Castration Resistant Prostate Cancer (mCRPC)

3.2.1. firstline treatment in mcrpc.

First-line treatment in men with mCRPC differ. Most trials explored the role of treatments after the failure of ADT alone.

Docetaxel was reported to improve OS compared to Mitoxantrone in the SWOG 99–16 trial. Docetaxel/Estramustine (every 3 weeks 60 mg/m 2 ) was compared to Mitoxantrone and prednisone (every 3 weeks 12 mg/m 2 ). Patients who received docetaxel had an overall survival of 17.5 months whereas patients who were treated with Mitoxantrone had an OS of only 15.6 months ( p = 0.02; HR = 0.80; 95% CI 0.67–0.97). There was a significant difference in rPFS:6.3 months (Docetaxel) vs. 3.2 months (Mitoxantrone) ( p < 0.001) [ 17 ].

The efficacy of abiraterone acetate before chemotherapy was shown in the placebo controlled COU-AA-302 trial. Patients who received abiraterone acetate + prednisone had superior OS than those in placebo + prednisone group (34.7 vs. 30.3 months HR 0.81, p = 0.0033). There was also a significant improvement in rPFS favoring AAP (16.5 months vs. 8.3 months; p < 0.0001) [ 18 ].

PREVAIL investigated the therapeutic benefit of enzalutamide in comparison to placebo in mCRPC in chemotherapy-naïve patients. Patients treated with enzalutamide had an OS of 32.4 months compared to 30.2 months in placebo group (HR = 0.71, 95% CI 0.60–0.84, p < 0.001). rPFS was significantly longer in patients who received enzalutamide (20.0 months vs. 5.4 months (HR = 0.186, 95% CI 0.15–0.23; p < 0.0001) [ 19 ].

The PROPEL trial investigated the combination of Olaparib + Abiraterone vs. Placebo + Abiraterone. This trial will be mentioned in detail in section “Molecular Therapies”.

Firstline options in CRPC are summarized in Table 4 .

Firstline options in CRPC.

3.2.2. Options after Pretreatment in mCRPC

For mCRPC patients who have already been treated with docetaxel, there are some therapeutic options, which will be listed below.

Cabazitaxel is a novel taxane with activity in docetaxel resistant CRPC. In the TROPIC 2013 trial, Cabazitaxel + prednisone showed a benefit in 2 year OS in comparison to mitoxantrone + prednisone (OS > 2 years in 15.9% (60/378) vs. 31/377 (8.2%). (odds ratio 2.11; 95% CI 1.33–3.33) [ 20 ].

The value of AAP in treatment of mHSPC has already been mentioned above. Additionally, in mCRPC it is a possible therapy option after docetaxel. In COU AA 301 study, AAP was compared to placebo/prednisone and led to an OS of 15.8 months in AAP group vs. 11.2 months in the placebo arm. ( p < 0.0001, HR = 0.74, 95% CI: 0.64–0.86). Median rPFS was 5.6 months (5.6–6.5) in AAP group and 3.6 months (2.9–5.5) in control group (HR = 0.66, 0.58–0.76; p < 0·0001) [ 21 ].

Enzalutamide has been mentioned above. In the AFFIRM trial, patients who received enzalutamide after docetaxel had a significantly longer OS than those who received placebo (OS 18.4 vs. 13.6 months; ( p < 0.001, HR = 0.63; 95% CI: 0.53–0.75)). There was also a statistically significant difference in rPFS: 8.3 months vs. 2.9 months ( p < 0.001, HR = 0.63; 95% CI: 0.53–0.75) that favored enzalutamide [ 22 ].

In patients with two or more symptomatic bone metastases and no visceral metastases, alpharadin (Radium 223) is also a possible treatment option. Besides symptom relief in bone metastases, it also led to a longer OS in ALSYMPCA (Radium 223 vs. Placebo in previous or no previous docetaxel). OS in patients who received Radium 223 was 14.9 months vs. 11.3 months in placebo group ( p = 0.002, HR = 0.61; 95% CI: 0.46–0.81) The most common hematologic AE in the Radium-223 group was anemia (187/600 pts.; 31%) whereas bone pain (300/600 pts.; 50%) and nausea (213/600 pts.; 36%) where most common nonhematologic AEs. [ 23 ].

In the CARD study, Cabazitaxel was compared to Abiraterone or Enzalutamide in patients with mCRPC who were treated with Doxetaxel and Abiraterone or Ezalutamide. In all, 255 patients were randomized in two groups: one group received Cabazitaxel (129 pts.), the other group received Abiraterone or Enzalutamide depending on which they had not received yet (126 pts.). The median overall survival was 13.6 months in the Cabazitaxel group and 11.0 months in the Abiraterone/Enzalutamide group (HR for death = 0.64; 95% CI, 0.46 to 0.89; p = 0.008). The median progression-free survival was 4.4 months in Cabazitaxel group vs. 2.7 months in the other group. (HR for progression or death =0.52; 95% CI, 0.40 to 0.68; p < 0.001). As a result, Cabazitaxel resulted in longer overall survival and progression-free survival [ 24 ].

Options after pretreatment are summarized in Table 5 .

Options after pretreatment in mCRPC.

4. Molecular Therapy

The incorporation of molecular diagnostics deepened our understanding of putative therapeutic avenues in mCRPC. BRCA 1 or 2 regulate homologous recombination (HR) and loss in BRCA function may occur as germline or sporadic alteration. BRCA deficient cancers are explicitly susceptible to PARP inhibitors. The clinically most advanced PARP inhibitor in mCRPC is olaparib. The PROfound study compared olaparib with AAP or enzalutamide in patients with alterations in HR repair (HRR) deficient CRPC after treatment with a new hormonal agent. BRCA 1 alteration was found in 8/256 pts in Olaparib group (3%) and 5/131 pts. in control group (4%). BRCA 2 alteration was found in 81/256 pts (32%) in the Olaparib group and 47/131 (36%) in the control group. In patients with at least one alteration in BRCA1, BRCA 2 or ATM, Olaparib achieved a superior rPFS (7.39 vs. 3.55 mo. (HR = 0.34; 95% CI: 0.25–0.47; p < 0.0001)) and OS (18.5 mo vs. 15.1 mo. hazard ratio for death = 0.64; 95% CI, 0.43 to 0.97; p = 0.02). In the overall population, the median OS at interim analysis was 17.5 months (Olaparib group) and 14.3 months (control group) (hazard ratio for death = 0.67; 95% CI, 0.49 to 0.93). Patients with BRCA alterations derived the largest benefit, which led to a restricted label in Europe. However, other HRR alterations seem to select for PARPi-sensitivity, but subgroups remain small and their predictive strength remains vague [ 25 ].

In the PROpel study, 796 patients with mCRPC were randomized to receive Olaparib + Abiraterone ( n = 399) vs. Placebo and Abiraterone ( n = 397). In an interim analysis, rPFS was longer in Olaparib + Abiraterone group irrespective of HRR status (24.8 vs. 16.6 months; HR = 0.66, 95% confidence interval [CI] 0.54–0.81; p < 0.0001). Data on OS were immature at interim analysis [ 26 ].

Based on these data, BRCA testing has entered the clinical routine in mCRPC.

Alterations of the PI3 kinase/AKT signaling pathway are common in CRPC. PTEN is a suppressor of this signaling pathway and its loss is frequently found in CRPC. PTEN loss is associated with an aggressive clinical course and subject for pharmacological intervention in late stage mCRPC. Ipatasertib is an AKT inhibitor and its clinical efficacy was tested in a pivotal trial. Patients with previously untreated asymptomatic or mildly symptomatic mCRPC were eligible. The combination of Ipatasertib and AAP showed a benefit in rPFS in patients with PTEN loss in comparison to AAP + placebo (18.5 months vs. 16.5 months p = 0.0335, HR = 0.77, 95% CI: 0.61–0.98). There was no significant benefit on PFS in the intention to treat population (16.6 months (Placebo) vs. 19.2 months (HR = 0.84 [95% CI 0·71–0.99]; p = 0.043) [ 27 ].

A new therapeutic modality was introduced with the development of systemic PSMA-targeted radio ligand therapy (RLT) in mCRPC. Lutetium-177-PSMA-617 (LU-PSMA) is a small molecule that binds specifically to PSMA, which enables ß particle therapy to adjacent tumor cells in CRPC. A positive diagnostic 68-Gallium PSMA PET scan is a prerequisite to select suitable patients for this molecular therapy.

The VISION trial tested LU-PSMA in previously treated mCRPC patients who were not candidates for chemotherapy. LU-PSMA showed a significant benefit in rPFS (8.7 vs. 3.4 mo. ( p < 0.001; HR = 0.40; 99.2% CI: 0.29–0.57)) and OS (15.3 vs. 11.3 mo. ( p < 0.001; HR = 0.62; 95% CI: 0.5–0.74)) in comparison to standard of care (best supportive care, which consisted of hormonal therapy, denosumab, bisphosphonates, radiation therapy or glucocorticoids) [ 28 ].

Another important trial which proved the effectiveness of PSMA radioligand therapy was TheraP. It included previously treated mCRPC patients who were deemed fit for chemotherapy and patients were randomized to receive LU-PSMA or Cabazitaxel. Patient selection was more stringent and permitted only patients with a match of PSMA- and FDG-PET activity. LU-PSMA RLT (up to six cycles; n = 98 pts.) was compared to Cabazitaxel (up to 10 cycles; n = 85 pts.). PSA response (defined as reduction of at least 50% from baseline), the primary endpoint, was shown in 66/98 (67%) pts who received PSMA RLT, but only 37/85 pts. (43%) who received Cabazitaxel ( p < 0.001). Grade 3–4 adverse events occurred in 32 (33%) patients in the PSMA RLT group vs. 45 (53%) in the Cabazitaxel group.

Overall, PSMA RLT showed improved efficacy and lower risk of grade 3–4 adverse events when compared to Cabazitaxel. However, the trial did not indicate major differences in OS in this trial and underlines the value of LU-PSMA in direct comparison to Cabazitaxel in mCRPC patients, which is considered a life-prolonging therapy [ 29 ].

Both BRCA 1/2 mutations and PSMA-positivity were predictive markers for treatment benefit. The molecular therapies are summarized in Table 6 .

Molecular therapies.

The most common adverse events related to molecular therapies are shown in Table 7 .

Most common adverse events related to molecular therapy.

4.1. Immunotherapy

Until now, immunotherapy has not been of great importance in the treatment of prostate cancer and did not improve clinical outcomes significantly. Current trials test the role of ICI in specific subgroups: KEYNOTE- 641 is a Phase 3, randomized, double-blind, placebo-controlled trial, which investigates Pembrolizumab/Placebo in combination with Enzalutamide in mCRPC patients who were not treated with abiraterone or progressed on Abiraterone and did not receive chemotherapy [ 30 ]. Keynote-921 is a Phase 3, randomized, double-blind, placebo-controlled trial which investigates pembrolizumab/placebo in combination with docetaxel and prednisone in mCRPC patients who have received novel hormonal agents but no chemotherapy before [ 31 ]. On 3 August 2022, the sponsor announced that the study did not meet its primary endpoints (improvement in overall survival and rPFS). KEYNOTE-991 is a Phase 3 trial to investigate the role of Pembrolizumab in combination with Enzalutamide and ADT versus Placebo in combination with Enzalutamide and ADT in mCRPC patients who did not receive novel hormonal agents before. The results of these trials are not available until 2025/2026 and could reform the rule of immunotherapy in prostate cancer [ 32 ]. Keynote-365 is a multicohort phase Ib/II study which tests pembrolizumab in combination with Olaparib (Cohort A), Docetaxel and Prednisone (Cohort B), Enzalutamide (Cohort C). In the results published so far, PSA response was reported in 9% of patients in cohort A, 28% in cohort B and 22% in cohort C. The final results of this study are not yet available [ 33 ].

4.2. Cell Based Immunotherapy

So far, cell based immunotherapy has not found its place in the treatment landscape of mCRPC. This could change in the future due to ongoing developments.

A therapy approach which was developed several years ago is supileucel-T. This is an active cell based autologous immunotherapy. Peripheral blood mononuclear cells are activated ex vivo with PA2024, a recombinant fusion protein of prostate antigen, which causes immune cell activation. Ultimately, mCRPC patients with an expected survival of at least 6 months received supileucel-T in a phase III trial ( n = 341 pts.). In all, 171 patients received placebo as a control group. The OS in the supileucel-T group was 25.8 months and 21.7 months in the placebo group. (HR for death in the sipuleucel-T group = 0.78; 95% confidence interval [CI], 0.61 to 0.98; p = 0.03) [ 34 ]. Although showing principal activity, supileucel-T is not available in routine practice anymore.

5. Vaccination

Vaccination against prostate cancer is not established in clinical practice. Nevertheless, there are studies that provided promising data. As an example, PROSTVAC, a PSA recombinant vaccinia vector, showed promising activity in mCRPC patients. Median OS was 8.5 months longer in pts who received PROSTVAC than in the control group ( p = 0.0061) [ 35 ]. However, confirmatory trials were negative and did not show a benefit in OS [ 36 ].

6. Bispecific T-Cell Engager

The most advanced bispecific T-cell engager in the therapy of prostate cancer is PSMA Bite. PSMA is expressed in prostate cancer cells and metastases and can be used to specifically target therapies to prostate cancer cells, such as for LU-PSMA radioligand therapy [ 28 ].

PSMA Bite is a new experimental treatment for mCRPC patients. PSMA Bite is a bispecific CD3 and PSMA antibody construct, which re-directs and activates T-cells to PSMA expressing cells.

Bispecific T-cell engager (BiTE) is already established in the treatment of other malignancies. Blinatumumab was the first approved BITE therapy. It is a bispecific monoclonal antibody construct that causes CD3 positive T-cells to recognize and target CD 19 positive B-cells. Blinatumumab is approved for patients with refractory or relapsed precursor B-ALL. Compared to chemotherapy, blinatumumab showed a survival benefit in patients with pretreated B-ALL: Median OS in the blinatumomab group was 7.7 months compared to 4.0 months in the chemotherapy group (HR = 0.71; 95% CI 0.55 to 0.93; p = 0.01) [ 37 ].

Based on promising data from the treatment of hematological diseases, the suitability of bite molecules for the treatment of solid tumors is currently being investigated.

A Phase I study of pasotuximab (PSMA Bite) tested its tolerability and activity in mCRPC. It included 68 patients in two cohorts of subcutaneous (s.c.) or intravenous (i.v.) application. These patients were pretreated with at least one taxane regimen and refractory to AAP or enzalutamide. Next, to evaluate the maximum tolerated dose in both cohorts, PSA response was investigated. In the subcutaneous cohort, every patient developed anti-drug antibodies, which led to the premature discontinuation of the s.c. application cohort.

PSA decline was −24.7% in pts. with s.c. treatment. In the i.v. group, median best PSA change was −22.0, −37.7 and −54.9% in 20, 40 and 80 µg/d dose cohorts. One patient in i.v. cohort had <50% PSA reduction for 50 weeks and stable disease for 337 days. Another patient in the i.v. cohort had nearly complete regression of lymphnode and bone metastases in PSMA-PET CT. PSA progression in long-term responders in i.v. cohort occurred after 11–17 months and indicates the principle and dose-dependent activity of this new modality. Most common adverse events in both cohorts were fever (81% in s.c. and 94% in i.v. cohort), injection site reaction in the s.c. cohort (24/31; 77%), chills (23% in s.c. and 69% in the i.v. cohort) and fatigue (36% in the s.c. and 31% in the i.v. cohort). Treatment-emergend AEs occurred in both cohorts. Most common were anemia (39%) in the s.c. cohort and decreased lymphocyte count (44%) and infections (31%) in the i.v. cohort [ 38 ]. Further trials to investigate the value and safety of PSMA Bite are ongoing.

Other targets than PSMA may be used for bispecific T-cell engager, such as Glypican-1 [ 39 ] and ADAM 17 (disintegrin and metalloproteinase 17) [ 40 ] or STEAP-1 [ 41 ], which are under investigation.

Overall, bispecific T-cell engager ( Figure 1 ) is a promising new therapy option with early signs of clinical activity. Of course, further clinical studies are necessary before they are ready for prime time, but early clinical trials are promising.

Bispecific T-cell engager. Modified according to Strohl et al. [ 42 ].

7. Conclusions

Prostate cancer is the most common solid cancer in men. In recent years, there have been major advances in the treatment of metastatic prostate cancer, which have pushed frontiers of survival expectations to new levels. ADT alone is not enough anymore for men with metastatic HSPC. Men with BRCA 1/2 alterations and with PSMA-positive cancers benefit from targeted treatment with PARPi or Lu-PSMA, respectively. However, castration resistant prostate cancer remains a deadly disease and new therapies are needed. The advent of molecular therapies, such as RLT or PARPi, advanced the field more recently and early clinical trials indicate promising new therapeutic approaches, which includes immunotherapies.

Funding Statement

This research received no external funding.

Author Contributions

Writing, original manuscript preparation: P.P.; editing and review: C.D., T.H., K.H. and M.W.; supervision: B.H. and V.G. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

P.P. has no conflicts of interest; C.D. Travels Fees and Advisory Board from Janssen-Cilag; T.H. has no conflicts of interest; M.W. has no conflicts of interest; B.H. has had advisory roles for ABX, AAA/Novartis, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen R&D, Lightpoint Medical, Inc., and Pfizer; has received research funding from Astellas, Bristol Myers Squibb, AAA/Novartis, German Research Foundation, Janssen R&D, and Pfizer; and has received compensation for travel from Astellas, AstraZeneca, Bayer and Janssen R&D. KH reports personal fees from Bayer, personal fees and other from Sofie Biosciences, personal fees from SIRTEX, non-financial support from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees from Siemens Healthineers, personal fees from GE Healthcare, personal fees from Amgen, personal fees from Novartis, personal fees from ymabs, all outside the submitted work. VG: Receipt of grants/research support: AstraZeneca, Novartis, BMS, MSD, Ipsen, Pfizer; receipt of honoria or consultation fees: AstraZeneca, BMS, Novartis, Apogepha, Ipsen, EISAI, MSD, MerckSerono, Roche, EUSAPharm, Janssen, Nanobiotix, ONO Pharmaceutical, Debiopharm; stock shareholder: AstraZeneca, BMS, SeaGen, MSD, GenMab; travel support: AstraZeneca, BMS, MerckSerono.

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The treatment landscape of metastatic prostate cancer

Affiliations.

• 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
• 2 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. Electronic address: [email protected].
• PMID: 34153403
• PMCID: PMC8403655
• DOI: 10.1016/j.canlet.2021.06.010

The treatment landscape of metastatic prostate cancer has evolved significantly over the past two decades. Several landmark phase 3 trials led to new drug approvals and rapid changes in therapy options for patients, including drugs with distinct mechanisms of action (e.g., hormonal, chemotherapy, radionuclide, immunotherapy, and targeted therapies). Therapies initially developed in later stages of the disease (metastatic castration resistant prostate cancer) have started to move earlier in the prostate cancer continuum, with new standards of care for metastatic hormone naive prostate cancer and non-metastatic castration resistant prostate cancer. Overall, patients are living longer with a better quality of life. However, despite these significant advances, prostate cancer remains a leading cause of cancer death globally. Disease heterogeneity and the emergence of therapy resistance remain significant barriers, and the identification and application of molecular biomarkers to guide the choice and sequencing of systemic agents are still in early stages. Here we discuss the current treatment landscape of metastatic prostate cancer, clinical challenges, and the emerging role of molecular biomarkers for targeting biologic subsets of advanced disease and co-targeting heterogenous resistance patterns.

Keywords: Androgen receptor pathway inhibitor; Castration resistance; Metastatic prostate cancer; Precision medicine; Treatment sequencing.

Copyright © 2021 Elsevier B.V. All rights reserved.

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Conflict of interest statement

Declaration of interests

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

The current landscape of systemic…

The current landscape of systemic therapies in prostate cancer

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Advances in Prostate Cancer Research

Nanoparticles are tested as a means to deliver drugs to prostate cancer cells.

NCI-funded researchers are working to advance our understanding of how to prevent, detect, and treat prostate cancer.  Most men diagnosed with prostate cancer will live a long time, but challenges remain in choosing the best treatments for individuals at all stages of the disease.

This page highlights some of the latest research in prostate cancer, including clinical advances that may soon translate into improved care, NCI-supported programs that are fueling progress, and research findings from recent studies.

Studying Early Detection for Men at High Risk

Men with certain inherited genetic traits are at increased risk for developing prostate cancer. Examples of such traits include inherited BRCA gene mutations and Lynch syndrome . No clear guidelines exist for when or how—or if—to screen men at high genetic risk for prostate cancer. 

NCI researchers are using magnetic resonance imaging (MRI) of the prostate in men at high risk of developing prostate cancer to learn more about how often and how early these cancers occur. They’re also testing whether regular scans in such men can detect cancers early, before they spread elsewhere in the body ( metastasize ).

Diagnosing Prostate Cancer

Improving biopsies for prostate cancer.

Traditionally, prostate cancer has been diagnosed using needles inserted into the prostate gland in several places under the guidance of transrectal ultrasound (TRUS) imaging to collect samples of tissue. This approach is called systematic biopsy .

However, ultrasound does not generally show the location of cancer within the prostate. It is mainly used to make sure the biopsy needles go into the gland safely. Therefore, biopsy samples using ultrasound guidance can miss cancer altogether. Or they may identify low-grade cancer while missing areas of high-grade , potentially more aggressive cancer, particularly in Black men.

Some doctors, concerned that a systematic biopsy showing only low-grade cancer could have missed a high-grade cancer, may suggest surgery or radiation. However, in some cases these treatments will be for a cancer that may have never caused a problem, which is considered overtreatment .

Using MRI and ultrasound . Scientists at NCI have developed a procedure that combines magnetic resonance imaging (MRI) with TRUS for more accurate prostate biopsies. MRI can locate potential areas of cancer within the gland but is not practical for real-time imaging to guide a prostate biopsy. The procedure, known as MRI-targeted biopsy, uses computers to fuse an MRI image with an ultrasound image. This lets doctors use ultrasound guidance to take biopsy samples of areas of possible cancer seen on MRI.

NCI researchers have found that combining MRI-targeted biopsy with systematic biopsy can increase the detection of high-grade prostate cancers while decreasing detection of low-grade cancers that are unlikely to progress. 

Testing machine learning . Researchers are testing the use of machine learning , also called artificial intelligence (AI), to better recognize suspicious areas in a prostate MRI that should be biopsied. AI is also being developed to help pathologist s who aren't prostate cancer experts accurately assess prostate cancer grade . Cancer grade is the most important factor in determining the need for treatment versus  active surveillance .

Finding small amounts of prostate cancer using imaging and PSMA

NCI-supported researchers are developing new imaging techniques to improve the diagnosis of recurrent prostate cancer. A protein called prostate-specific membrane antigen (PSMA) is found in large amounts—and almost exclusively—on both cancerous and noncancerous prostate cells. By fusing a molecule that binds to PSMA to a compound used in PET  imaging, scientists have been able to see tiny deposits of prostate cancer that are too small to be detected by regular imaging.

The Food and Drug Administration (FDA) has approved two such compounds for use in PSMA-PET imaging of men with prostate cancer. These approvals are for men whose cancer may have spread to other parts of the body but is still considered curable, either with surgery or other treatments.

The ability to detect very small amounts of metastatic prostate cancer could help doctors and patients make better-informed treatment decisions. For example, if metastatic cancer is found when a man is first diagnosed, he may choose an alternative treatment to surgery because the cancer has already spread. Or doctors may be able to treat cancer recurrence—either in the prostate or metastatic disease—earlier, which may lead to better survival. Studies are being done to determine if such early detection can improve outcomes.

As part of the Cancer Moonshot℠ , NCI researchers are testing whether PSMA-PET imaging can also identify men who are at high risk of their cancer recurring. Such imaging may eventually be able to help predict who needs more aggressive treatment—such as radiation therapy in addition to surgery—after diagnosis.

Research teams are also looking at:

• whether certain patterns seen on PSMA-PET tests taken over time may indicate an increased risk of recurrence after initial treatment
• how small metastases discovered with PSMA change over time , with or without treatment

New Prostate Cancer Treatments

Standard treatments for prostate cancer that has not spread elsewhere in the body are surgery or radiation therapy, with or without hormone therapy . 

Active surveillance is also an option for men who have a low risk of their cancer spreading. This means monitoring the cancer with regular biopsies and other tests, and holding off on treatment unless there is evidence of progression. Rates of active surveillance more than doubled between 2014 and 2021 , to almost 60% of US men diagnosed with low-risk prostate cancer. 

Hormone therapy for prostate cancer

Over the last decade, several new approaches to hormone therapy for advanced or metastatic prostate cancer have been approved for clinical use.

Many prostate cancers that originally respond to treatment with standard hormone therapy become resistant over time, resulting in castrate-resistant prostate cancer  (CRPC). Four newer drugs have been shown to extend survival in some groups of men with CRPC. All inhibit the action of hormones that drive CRPC:

• enzalutamide (Xtandi) 
• abiraterone (Zytiga)
• darolutamide (Nubeqa)
• apalutamide (Erleada)

These drugs are now also used in some people whose prostate cancer still responds to standard hormone therapies but has spread elsewhere in the body (metastasized).

Scientists are continuing to study novel treatments and drugs, along with new combinations of existing treatments, in men with metastatic and castrate-resistant prostate cancer.

Hormone therapy for biochemically recurrent prostate cancer

A biochemical recurrence is a rise in the blood level of PSA in people with prostate cancer after treatment with surgery or radiation. In 2023, the FDA approved enzalutamide, given alone or with another drug called leuprolide, for some men who have a biochemical recurrence and are at high risk of their cancer spreading but don’t have signs on regular imaging that their cancer has come back.

Use of this drug combination can improve how long these men live without their cancer spreading. But it’s not yet known if using the drugs in this manner improves how long people live overall. Researchers are trying to determine which patients will benefit most from these types of treatments.

PARP inhibitors for prostate cancer

A PARP inhibitor is a substance that blocks an enzyme in cells called PARP. PARP helps repair DNA when it becomes damaged. Some prostate tumors have genetic changes that limit their ability to repair DNA damage. These tumors may be sensitive to treatment with PARP inhibitors. Some people also inherit genetic factors that limit their body’s ability to repair DNA damage. Prostate tumors in such people can also be treated with PARP inhibitors.  

Two PARP inhibitors, olaparib (Lynparza) and rucaparib (Rubraca) , have been approved for use alone in some men whose prostate cancer has such genetic changes and has metastasized , and whose disease has stopped responding to standard hormone treatments alone.

Ongoing studies are looking at combining PARP inhibitors with hormone therapies. Since 2023, the FDA has approved three such combinations for some men with metastatic prostate cancer:

• the hormone therapy enzalutamide (Xtandi) with the PARP inhibitor, talazoparib (Talzenna)
• the hormone therapy abiraterone (Zytiga) with the PARP inhibitor olaparib (Lynparza)
• the hormone therapy abiraterone with the PARP inhibitor niraparib (Akeega)

Immunotherapy: vaccines for prostate cancer

Immunotherapies are treatments that harness the power of the immune system to fight cancer. These treatments can either help the immune system attack the cancer directly or stimulate the immune system in a more general way.

Vaccines and checkpoint inhibitors are two types of immunotherapy being tested in prostate cancer. Treatment vaccines are injections that stimulate the immune system to recognize and attack a tumor.

One type of treatment vaccine called sipuleucel-T (Provenge) is approved for men with few or no symptoms from metastatic CRPC.

Immunotherapy: checkpoint inhibitors for prostate cancer

An immune checkpoint inhibitor is a type of drug that blocks proteins on immune cells, making the immune system more effective at killing cancer cells.

Two checkpoint inhibitors,  pembrolizumab (Keytruda)  and dostarlimab (Jemperli) have been approved for the treatment of tumors, including prostate cancers, that have specific genetic features . Pembrolizumab has also been approved for any tumor that has metastasized and has a high number of genetic mutations .

But relatively few prostate cancers have these features, and prostate cancer in general has largely been resistant to treatment with checkpoint inhibitors and other immunotherapies, such as CAR T-cell therapy .

Research is ongoing to find ways to help the immune system recognize prostate tumors and help immune cells penetrate prostate tumor tissue. Studies are looking at whether combinations of immunotherapy drugs, or immunotherapy drugs given with other types of treatment, may be more effective in treating prostate cancer than single immunotherapies alone.

PSMA-targeted radiation therapy

Scientists have developed targeted therapies based on PSMA, the same protein that is used for imaging prostate cancer. For treatment, the molecule that targets PSMA is chemically linked to a radioactive  substance. This new compound can potentially find, bind to, and kill prostate cancer cells throughout the body.

In a recent clinical trial, men with a type of advanced prostate cancer who received a PSMA-targeting drug lived longer than those who received standard therapies . This trial led to FDA approval of the drug,  Lu177-PSMA-617 (Pluvicto) , to treat some people with metastatic prostate cancer who had previously received chemotherapy. 

An ongoing study is testing the use of Lu177-PSMA-617 in some people with metastatic prostate cancer who haven't yet received chemotherapy. Other clinical trials are testing PSMA-targeting drugs in patients with earlier stages of prostate cancer, and in combination with other treatments, including targeted therapies like PARP inhibitors and immunotherapy.

Personalized clinical trials for prostate cancer

Research is uncovering more information about the genetic changes that happen as prostate cancers develop and progress. Although early-stage prostate cancer has relatively few genetic changes compared with other types of cancer, researchers have learned that metastatic prostate cancers usually accumulate more changes as they spread through the body.

These changes may make men with metastatic prostate cancers candidates for what are called “basket” clinical trials of new drugs. Such trials enroll participants based on the changes found in their cancer, not where in the body the cancer arose. In the NCI-MATCH trial , a high percentage of enrolled men with advanced prostate cancer had genetic changes that could potentially be targeted with investigational drugs.

NCI-Supported Research Programs

Many NCI-funded researchers working at the National Institutes of Health campus, as well as across the United States and world, are seeking ways to address prostate cancer more effectively. Some of this research is basic, exploring questions as diverse as the biological underpinnings of cancer and the social factors that affect cancer risk. And some is more clinical, seeking to translate basic information into improving patient outcomes. The programs listed below are a small sampling of NCI’s research efforts in prostate cancer.

• The Cancer Biomarkers Research Group promotes research on cancer biomarkers and manages the Early Detection Research Network (EDRN) . EDRN is a network of NCI-funded institutions that are collaborating to discover and validate early detection biomarkers.
• Within the  Center for Cancer Research , the Prostate Cancer Multidisciplinary Clinic (PCMC) provides comprehensive consultations on diagnosis and treatment options to people with newly-diagnosed prostate cancer. 
• The Prostate Specialized Programs of Research Excellence (Prostate SPOREs) are designed to quickly move basic scientific findings into clinical settings. The Prostate SPOREs support the development of new therapies and technologies and studies to better understand how to prevent, monitor, and treat prostate cancer.
• The NCI Cancer Intervention and Surveillance Modeling Network (CISNET)  focuses on using modeling to improve our understanding of which men are most likely to benefit from PSA-based screening. CISNET also studies treatment strategies for prostate cancer and approaches for reducing prostate cancer disparities.
• The NCI Genitourinary Malignancies Center of Excellence (GUM-COE) brings together scientists studying genitourinary cancers (GU) from across NCI’s Center for Cancer Research and the Division of Cancer Epidemiology and Genetics, as well as investigators who study GU malignancies in other institutes of NIH. The goal is to provide a centralized resource and infrastructure to accelerate the discovery, development, and delivery of interventions for the prevention, diagnosis, and treatment of these cancers.
• The Research on Prostate Cancer in Men with African Ancestry (RESPOND) study is the largest-ever coordinated research effort to study biological and non-biological factors associated with aggressive prostate cancer in African American men. The study , launched by NCI and the National Institute on Minority Health and Health Disparities in partnership with the Prostate Cancer Foundation, is looking at the environmental and genetic factors related to the aggressiveness of prostate cancer in African American men to better understand why they disproportionally experience aggressive disease.

Clinical Trials

NCI funds and oversees both early- and late-phase clinical trials to develop new treatments and improve patient care. Trials are available for prostate cancer  prevention , screening , and treatment .

Prostate Cancer Research Results

The following are some of our latest news articles on prostate cancer research:

• Enzalutamide Gets Added Approval for Prostate Cancer That Hasn’t Spread
• FDA Approves New Initial Treatment Option for Some Metastatic Prostate Cancers
• Is a Genomic Test Better at Finding Aggressive Prostate Cancer?
• Active Surveillance for Low-Risk Prostate Cancer Continues to Rise
• Darolutamide Extends Survival for Some People with Metastatic Prostate Cancer
• Shorter, More Intensive Radiation Safe after Surgery for Prostate Cancer

View the full list of Prostate Cancer Research Results and Study Updates .

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Could immunotherapy finally break through in prostate cancer?

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The first therapeutic cancer vaccine, approved more than a decade ago, targeted prostate tumours. The treatment involves extracting antigen-presenting cells — a component of the immune system that tells other cells what to target — from a person’s blood, loading them with a marker found on prostate tumours, and then returning them to the patient. The idea is that other immune cells will then take note and attack the cancer.

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The figure shows median survival by year of diagnosis, stratified by age at diagnosis of de novo metastatic prostate cancer in SEER and VHA registries. Error bars represent 95% CIs of the median.

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Schoen MW , Montgomery RB , Owens L , Khan S , Sanfilippo KM , Etzioni RB. Survival in Patients With De Novo Metastatic Prostate Cancer. JAMA Netw Open. 2024;7(3):e241970. doi:10.1001/jamanetworkopen.2024.1970

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Survival in Patients With De Novo Metastatic Prostate Cancer

• 1 Saint Louis Veterans Affairs Medical Center, Saint Louis, Missouri
• 2 Saint Louis University School of Medicine, Saint Louis, Missouri
• 3 VA Puget Sound Healthcare System, Washington
• 4 Fred Hutchinson Cancer Center, Seattle, Washington
• 5 University of Washington School of Medicine, Seattle
• 6 Washington University in St Louis School of Medicine, Saint Louis, Missouri

Overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC) has improved in clinical trials over the last 20 years. 1 , 2 It is unclear whether new treatments have translated to improvements in survival rates in clinical practice. We sought to quantify trends in OS among patients with newly diagnosed de novo (synchronous) mHSPC in 2 national registries in the United States: the Surveillance, Epidemiology, and End Results 17 (SEER) registry database and the Veterans Health Administration (VHA) registry database.

This cross-sectional study was approved by the St Louis Veterans Affairs institutional review board and granted a waiver of informed consent due to its retrospective nature. Patients diagnosed from 2000 to 2019 were included if stage at first diagnosis of prostate cancer was distant metastasis from SEER or VHA Oncology registry. Patients in VHA were observed until death or April 2022. Cox proportional hazard modeling was used to assess mortality risk by age and calendar interval.

This study was conducted according to the STROBE reporting guideline. Statistical analysis was performed using SAS version 9.4 (SAS Institute) from July to September 2022. Two-sided P  < .05 was considered statistically significant.

This study included 58 859 patients who were identified in SEER (median [IQR] age, 72 [64-81] years) and 14 904 patients in VHA (median [IQR] age, 73 [65-81] years). From the years 2000 to 2004 to the years 2015 to 2019, median OS increased from 23.0 to 30.0 months in SEER (hazard ratio [HR], 0.80 [95% CI, 0.77-0.82]); median OS increased from 25.6 to 30.9 months in VHA (HR, 0.91 [95% CI, 0.87-0.96]) ( Figure ). Among patients younger than 70 years, median OS increased from 31.0 to 40.0 months (HR, 0.78 [95% CI, 0.74-0.82]) in SEER and 34.3 to 42.2 months (HR, 0.87 [95% CI, 0.80-0.95]) in VHA. Among patients aged 70 years or older, increases were more modest; from 19.0 to 24.0 months in SEER (HR, 0.83 [95% CI, 0.80-0.86]) and from 21.6 to 25.6 months in VHA (HR, 0.94 [95% CI, 0.88-1.00]).

This cross-sectional study found that median OS in de novo mHSPC was similar in SEER and VHA and had improved significantly in the US population from 2000 to 2019, particularly in patients younger than 70 years. The improvements in OS mirror those observed in other countries 3 and are likely due to the increased use of combination therapy. 4 Our results suggest that new treatment paradigms may contribute to longer OS in clinical practice, which is the ideal setting to measure improvements in outcomes as treatments change.

Increased OS from trials cannot be assumed to reflect improvements in disease management in clinical practice. The OS of men with mHSPC is lower in clinical practice than in clinical trials as patients are typically older with more comorbidities. Second, trials that test similar clinical scenarios can produce drastically disparate OS. For example, the median control group OS was 36.5 months in LATITUDE, 2 which is shorter than the median control group OS of 70.2 months in SWOG-S1216, 1 even though both trials had similar control groups and started enrollment in 2013.

Our results highlight the poor OS in patients over 80 years of age, with little improvement over time. This finding emphasizes the need to understand toxic effects vs benefits and competing risks for mortality in older patients. Older patients with comorbid disease may not benefit from new therapies and may have higher risk of adverse events. Tailoring treatment for mHSPC based on comorbidities 5 or genetic features 6 may improve patient outcomes. This study is limited by lack of comorbidity data; furthermore, because it is observational, causality cannot be determined.

With improved detection of mHSPC, we expect that more patients will be determined to have mHSPC at diagnosis with smaller burden of disease and with longer survival due to stage migration rather than from improvements in treatment. Separating the effects of treatment from the effects of earlier mHSPC diagnosis will be more complex in the future.

Accepted for Publication: January 20, 2024.

Published: March 12, 2024. doi:10.1001/jamanetworkopen.2024.1970

Open Access: This is an open access article distributed under the terms of the CC-BY License . © 2024 Schoen MW et al. JAMA Network Open .

Corresponding Author: Martin W. Schoen, MD, MPH, St Louis Veterans Affairs Medical Center, 915 N Grand Blvd, St Louis, MO 63105 ( [email protected] ).

Author Contributions: Dr Schoen had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Schoen, Owens, Etzioni.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Schoen, Owens, Etzioni.

Critical review of the manuscript for important intellectual content: Montgomery, Owens, Khan, Sanfilippo, Etzioni.

Statistical analysis: Schoen, Owens, Etzioni.

Obtained funding: Schoen.

Administrative, technical, or material support: Khan.

Supervision: Schoen, Montgomery, Etzioni.

Conflict of Interest Disclosures: Dr Schoen reported personal fees from Pfizer outside the submitted work. Dr Khan reported grants from the US Department of Defense, salary from the Foundation for Barnes-Jewish Hospital Salary Support, and salary from the Siteman Cancer Center outside the submitted work. Dr Sanfilippo reported grants from the American Cancer Society, grants from the National Institutes of Health, National Heart, Lung, and Blood Institute, grants from the American Society of Hematology, payment of personal fees from the Health Services Advisory Group for work as a consultant, and payment of personal fees from Quinn Johnston for expert case review outside the submitted work. No other disclosures were reported.

Funding/Support: This study was supported by the Prostate Cancer Foundation Igor Tulchinsky, Robert Taubman and Richard Sandler – PCF VAlor Young Investigator Award and Department of Defense grant No. W81XWH-22-1-0602, both to Dr Schoen.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See the Supplement .

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• Published: 01 July 2024

Seminal Papers in Urology: Darolutamide and survival in metastatic, hormone-sensitive prostate cancer

• Claris Oh 1 &
• Michael O’Callaghan 1 , 2 , 3  

BMC Urology volume  24 , Article number:  135 ( 2024 ) Cite this article

Metrics details

The ARASENS trial recruited 1306 men with metastatic hormone sensitive prostate cancer. It investigated the effect of androgen deprivation therapy (ADT) and systemic therapy docetaxel in combination with a third novel drug – daralutamide, compared with placebo on overall survival. Triple therapy with ADT, docetaxel and darolutamide resulted in improved overall survival rates as compared with ADT, docetaxel and placebo (HR 0.68; 95% CI, 0.57–0.80; p  < 0.001). The side effect profile for both treatments was similar. This randomised, double blinded, placebo controlled study, was assessed to have a low risk of bias using the Cochrane Risk of Bias 2 tool.

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The clinical problem

Prostate cancer is a common diagnosis, and its prevalence is expected to increase as the population ages. The disease is also the sixth leading cause of death amongst men [ 1 ]. This is despite having significant advances in treatment of prostate cancer in the recent years, with development of new therapies and drugs approved for treatment of metastatic prostate cancer. Current guidelines by European Association of Urology (EAU) [ 2 ] and American Urological Association (AUA) [ 3 ] recommend offering all patients with metastatic hormone sensitive prostate cancer (mHSPC) a combination of androgen-deprivation therapy (ADT) plus systemic therapy docetaxel. There have also been previous trials supporting the addition of an androgen-receptor pathway inhibitor like abiraterone [ 4 ], enzalutamide [ 5 ] or apalutamide [ 6 ] to ADT. Triple therapy with ADT, docetaxel and the above-mentioned androgen-receptor pathway inhibitors had also been investigated, with varying results [ 7 , 8 ].

Darolutamide is a novel drug which has been shown to have significant benefits to survival rates in non-metastatic, castrate-resistant prostate cancer. Combinations with ADT were improved survival rates in comparison to ADT alone [ 9 ]. Through a randomised, double-blind, placebo-controlled trial, Smith et al. compared the survival rates of standard therapy of ADT plus docetaxel, with the addition of androgen-receptor pathway inhibitor darolutamide to the two drugs. The results were published in The New England Journal of Medicine in March 2022 [ 10 ].

Adult patients above the age of 18, with confirmed prostate cancer through histology or cytology and radiologically proven metastasis were eligible to enter the trial. Other inclusion criteria included having an Eastern Cooperative Oncology Group status of 0 to 1.

The primary outcome measure of overall survival was defined as the duration from time of randomisation to time of death, regardless of cause. Secondary outcome measures included time to progression of disease to being castrate resistant or initiation of systemic chemotherapy, as well as less subjective outcomes such as worsening symptoms measured through pain scores.

All patients recruited in the study underwent ADT or orchidectomy within 12 weeks before randomisation, and also had received six cycles of docetaxel. Patients also received doses of oral steroids to prevent hypersensitivity reactions and fluid retention according to clinician discretion.

Randomisation to receiving either darolutamide or placebo was in a 1:1 ratio, and was adjusted for metastasis stage according to the TNM system and serum levels of ALP. This was conducted by separate personnel, through a computer-generated randomisation list. The study aimed for 90% power to detect a 25% decrease in risk of death in the darolutamide group versus placebo group, and achieved this by recruiting total of 1306 patients across multiple sites in multiple countries. Patients were assessed based on the treatment they received.

There was equal distribution of the baseline characteristics between the two study groups which suggests that randomisation was implemented well. Only one and three patients were excluded from full analysis and safety analysis set respectively.

Summary of findings

There was a 32.5% reduction in risk of death for patients who received darolutamide as compared to those who received placebo, representing a significant improvement in overall survival (hazard ratio, 0.68; 95% confidence interval [CI], 0.57 to 0.80; P  < 0.001). Overall survival rate at four years was 62.7% in the darolutamide group and 50.4% in placebo group. The patients who were allocated to receive darolutamide with ADT and docetaxel also performed better in secondary outcomes than those in the placebo group.

Adverse event rate was similar in the two groups, with the most commonly reported being alopecia, followed by neutropenia, fatigue and anaemiaIn the darolutamide group 13.5% of patients with adverse event led to their discontinuation of the drug and only 10.5% in placebo group.

Assessment of evidence

The ARASENS phase 3 trial discussed in this paper is a large, multicentre, international study involving 23 countries and spanning five continents. There is good representation of not only race and cultures but also a wide range of healthcare systems.

There was a low risk of bias with appropriate steps taken to ensure adequate blinding of the patients, investigators and sponsors. Patients were analysed under their Intention to Treat groups and there were minimal missing data to affect the study results significantly. According to the Cochrane risk-of-bias assessment [ 11 ], the study has a low risk of bias in all domains. Although it should be acknowledged that the study was sponsored by Bayer and Orion Pharm, which might represent a potential risk for bias. The sponsors were involved in data analysis, interpretation, authorship and manuscript writing.

Future research

Future efforts could be directed to comparing the overall survival rates between having double therapy darolutamide and ADT versus ADT and docetaxel. Given that most of the adverse effects reported in this study are well known side effects from docetaxel, patients could potentially benefit from a reduction in the number of chemotherapy drugs they receive.

The trial could also be expanded to include patients of poor ECOG scores. This additional data is likely to become available in real world evidence studies (noting the non-randomised nature of this study type) and will be useful in assessing the generalisability of the study results. In addition, comparing adverse effects with alternative second generation androgen receptor inhibitors will be important, particularly in the context of similar efficacy [ 12 ].

ADT treatment of prostate cancer patients is becoming increasingly complex. This study demonstrates that darolutamide is beneficial in the setting of metastatic disease, and adds to data showing a benefit to men with non-metastatic castrate resistant disease [ 13 ]. These two patient settings are common targets for second generation androgen deprivation medications. To date, ADT monotherapy treatment of low risk and intermediate disease has not been demonstrated beneficial, and has limited application in high risk settings. Increasing focus on accurate diagnostic staging, stratification and medication combinations particularly minimising adverse events will likely characterise this field in the near term.

Data availability

This paper uses no primary data.

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The ARASENS trial: Smith MR, Hussain M, Saad F, et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. New England Journal of Medicine. 2022;386(12):1132-1142.

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Oh, C., O’Callaghan, M. Seminal Papers in Urology: Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. BMC Urol 24 , 135 (2024). https://doi.org/10.1186/s12894-024-01507-7

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FDA fast-tracks personalized therapy for hard-to-treat-prostate cancer

The US Food and Drug Administration (FDA) has green-lit the fast-tracking of an innovative personalized treatment for advanced prostate cancer following a promising clinical trial where the cancer disappeared completely in almost 40% of participants.

Prostate cancer needs testosterone to grow. In metastatic castration-resistant prostate cancer (mCRPC), an advanced form of the disease, the cancer continues growing despite a reduction in testosterone brought about by chemical or surgical castration. As such, mCRPC has few treatment options and carries a high mortality rate.

So, the FDA’s grant of Fast Track designation to an innovative combination drug/device treatment for mCRPC developed by Florida-based biopharmaceutical company Syncromune Inc. is welcome news.

“We believe that Fast-Track designation for SYNC-T SV-102 will significantly aid our development goals for this therapy for men with difficult-to-treat prostate cancer,” said Charles Link, MD, Executive Chairman of Syncromune. “We look forward to initiating trials at multiple US sites later this year to expand our efforts to develop the SYNC-T SV-102 therapy.”

A Fast Track designation facilitates the development and expedites the review of drugs for serious conditions and is intended to address an unmet medical need. To quote the FDA, “The purpose is to get important new drugs to the patient earlier.”

SYNC-T takes advantage of prostate cancer’s immunologically ‘cold’ tumor microenvironment, meaning it’s not likely to trigger a strong immune response because cold tumors tend to be surrounded by cells that prevent T cells from attacking and killing the tumor cells. Cancer immunotherapies are designed to stimulate and strengthen the body’s antitumor immune response, but existing therapies struggle to overcome this cold microenvironment. In contrast, SYNC-T’s novel mechanism of action stimulates a body-wide antitumor immune response to mCRPC.

The first step involves inserting a probe directly into the primary or metastatic tumor using a process similar to that used routinely by urologists to take a prostate biopsy. Part of the tumor is frozen, causing its cells to fracture and release immune-stimulating neoantigens, tumor-specific antigens produced by mutated tumor cells. In effect, this process creates a personalized cancer vaccine within the patient’s body that switches on their immune system.

The next step is to infuse a drug called SV-102, comprised of a combination of pharmaceutical ingredients, into the ‘fractured’ area of the tumor. The combination approach activates cancer-fighting T cells to mount a body-wide attack on the primary tumor and its metastases.

A Phase 1 clinical trial of SYNC-T SV-102 showed that it was safe and effective . Fifteen subjects with mCRPC were enrolled. For most, the cancer had spread to their bones, and previous treatments had failed. They were treated with SYNC-T SV-102 therapy every four weeks for up to 12 cycles, and their response to treatment was evaluated every eight weeks. The overall response rate of the 13 subjects whose response was evaluated was 85%, with five complete responses and six partial responses. A ‘complete response’ is when all signs of cancer in the body disappear, and a ‘partial response’ means a decrease in tumor size or amount of cancer in the body.

The response rate to SYNC-T is notable given the advanced stage of the subjects’ cancer and that standard treatments typically produce a response rate of 20% to 40% .

“The Fast-Track designation for SYNC-T SV-102 therapy signifies another step forward in bringing our potentially groundbreaking therapy to patients who need it most,” said Eamonn Hobbs, CEO and co-founder of Syncromune.

Source: Syncromune

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Metastatic Prostate Cancer Treatments

• PSA Test for Prostate Cancer
• Prostate Cancer Screening Guidelines
• Prostate Biopsy
• Prostate Cancer Active Surveillance Program
• Radical Prostatectomy (Prostate Cancer Surgery)
• Side Effects of Radical Prostatectomy (Prostate Cancer Surgery)
• Radiation Therapy for Prostate Cancer
• Brachytherapy for Prostate Cancer
• Focal Therapies for Prostate Cancer
• Hormone Therapy, Chemotherapy, and Immunotherapy for Prostate Cancer
• Follow-Up Care & Support for Prostate Cancer

Metastatic prostate cancer is cancer that has spread to other parts of the body. Treatments for metastatic prostate cancer are called systemic therapies. These drugs move throughout your body to attack cancer cells wherever they are. Some systemic therapies can reduce the side effects of metastatic disease. Given together, these treatments help people with metastatic prostate cancer live longer, better lives.

There are more treatment options for metastatic prostate cancer than ever before. Some drugs that work well became available recently. They include treatments for cancer that already spread at the time you are diagnosed. They also include treatments for cancer that spreads after radical prostatectomy surgery or radiation therapy .

The 3 main types of systemic therapy are hormone therapy, chemotherapy, and immunotherapy.

Hormone Therapy for Metastatic Prostate Cancer

Hormone therapy slows or blocks prostate cancer cells from growing. Testosterone is a male sex hormone. It’s made when hormones from your pituitary gland (a gland in your brain) cause your testes (testicles) to make sperm.

Testosterone can cause prostate cancer cells to grow. Hormone therapy lowers the amount of testosterone your testicles make. It also blocks the action of testosterone and other male hormones.

Some prostate tumors, however, become resistant to these drugs after months or years of treatment. This is called castration-resistant prostate cancer. There are more treatment options for castration-resistant prostate cancer than ever before.

Chemotherapy for Metastatic Prostate Cancer

Chemotherapy is medication that kills cancer cells, given by mouth or intravenously (put into your vein). Chemotherapy for prostate cancer is an important treatment option when the disease has metastasized (spread). If you have cancer that has spread to your bones, chemotherapy can help you live longer, with less pain. Docetaxel (Taxotere ® ) is considered the standard of care in chemotherapy for prostate cancer that is resistant to hormone therapy. It works by damaging the structure of prostate cancer cells.

Another chemotherapy drug for treating castration-resistant prostate cancer is cabazitaxel (Jevtana ® ). It’s also used by people with metastatic prostate cancer that has grown while they are taking docetaxel.

Immunotherapy for Metastatic Prostate Cancer

Immunotherapy uses the power of the immune system to target cancer cells. MSK has been a leader in developing immunotherapy treatments for many cancers.

The first immunotherapy treatment for people with advanced metastatic prostate cancer approved by the FDA was sipuleucel-T (Provenge ® ). The drug is made by removing a person’s immune cells and then engineering them to fight prostate cancer cells. The immune cells are then put back into the body. This drug can help people with metastatic prostate cancer live longer.

Checkpoint Inhibitors To Treat Prostate Cancer

More recently, MSK led a clinical trial of a type of immunotherapy called checkpoint inhibitors . Researchers studied the checkpoint inhibitor pembrolizumab (Keytruda ® ) . They found that a small number of people whose metastatic prostate cancers have a specific genetic alteration respond to Keytruda. Genetic testing of the tumor can tell us if someone with prostate cancer is likely to respond to the drug.

Systemic Radiation Treatments for Prostate Cancer

Another type of systemic therapy is called radiotherapeutics (or radiotherapies). It uses very small amounts of radioactive materials. MSK medical oncologists (cancer doctors) and nuclear medicine doctors work as a team to deliver this treatment to our patients.

A drug called radium-223 (Xofigo ® ) is used to treat advanced prostate cancer with bone metastases (cancer that has spread to the bones). Radium-223 delivers a very strong form of radiation to bone metastases. This drug has few side effects, and can help you live longer.

How MSK Is Improving The Targeting of Prostate Cancer Cells

Newer radiation therapy treatments target prostate cancer cells instead of the surrounding bone. These drugs can treat bone metastases as well as disease in other areas of the body. One treatment uses a type of radiation called 177 Lu-PSMA-617. It’s delivered to a prostate cancer protein that is called prostate specific membrane antigen (PSMA).

To see if this treatment will work, we use an imaging test called a PSMA PET scan. It shows us if there is enough PSMA on the prostate cancer for treatment with 177 Lu-PSMA-617. This treatment can prevent bone fractures and help you live longer, with a better quality of life.

In 2022, the FDA approved this treatment for people who already had hormonal treatments and chemotherapy. MSK also has many clinical trials that research new radiotherapies for this disease.

Other Systemic Treatments for Prostate Cancer

Many other systemic therapies are in the late stages of development. MSK medical oncologists are developing new treatments for prostate cancer. Our patients can join our clinical trials to access them.

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Clinical trial could lead to new 'gold standard' test for prostate cancer detection

by Gillian Rutherford, University of Alberta

A University of Alberta study shows that PET/CT imaging using a new tracing agent is more accurate at determining the extent of prostate cancer than the current standard MRI for intermediate and high-risk cases.

In research published this week in the journal JAMA Oncology , the researchers report that the new test correctly predicted the location and margin of tumors in 45% of cases—nearly twice as often as the rate of 28% for MRI.

"This is very important because we make a lot of treatment decisions based on where the cancer is in the prostate ," explains Adam Kinnaird, assistant professor of surgery and adjunct assistant professor of oncology, as well as the Frank and Carla Sojonky Chair in Prostate Cancer Research and a member of the Cancer Research Institute of Northern Alberta.

"If you're having your prostate removed and the cancer is sneaking outside of the prostate, then we go a little bit wider with our treatment margins so we don't leave any cancer behind. If you're having radiation to your prostate, the radiation oncologist sometimes provides a boost to the center of the cancer for better cancer control," Kinnaird says. "This imaging test gives us a better degree of accuracy in terms of where exactly we need to treat."

Potential new gold standard for testing

The test involves injecting a new radioactive prostate-tumor-specific tracer called 18F-PSMA-1007 into the blood of patients, then tracking it using a combination of positron-emitting tomography (PET) and computerized tomography (CT). Previous studies of PET/CT scans using other tracing agents have not proven as useful, Kinnaird says.

Both the PET/CT and MRI tests were performed within two weeks of each other on 134 Alberta men who were about to undergo radical prostatectomy —surgery that involves removing the prostate gland, surrounding tissues and nearby lymph nodes. The accuracy of the tests' predictions were then compared with the size and location of the actual tumors later found by surgeons.

"This clinical trial has great implications for clinical practice worldwide," says Kinnaird, explaining that he expects the PET/CT scan using the new tracer to become the gold standard.

The test involves a small dose of radiation exposure, but Kinnaird says no patients in the study experienced adverse reactions. He expects that the test will eventually replace other CT and bone scans that are currently required for prostate cancer patients, meaning fewer hospital visits, less time waiting for results and less exposure to radiation for patients, but that will require further study.

"It will be very exciting if you can get more accurate information and replace three tests with one test , because these scans are only available in Edmonton or Calgary," says graduate research fellow Patrick Albers, a co-author on the study.

The positive results from this trial have already prompted another clinical trial led by Kinnaird to determine whether the PET/CT scan can be used to guide ablation, a procedure that uses energy such as heat, cold or electricity to kill cancer cells within the prostate.

The new imaging agent is offered at only a few treatment centers across the country while it awaits Health Canada approval, but the Alberta government has just announced $3 million for 2,000 men to have the new scans in the meantime.

Ensuring better outcomes for Black men

A second recently published study from Kinnaird's research team shows that Black men with prostate cancer have similar outcomes to those of other men in Alberta. However, Black men are diagnosed an average of two years earlier—at age 64 rather than 66—leading Kinnaird to recommend that they be offered routine screening at 45 rather than 50.

Published in JAMA Network Open , the study was based on data from the Alberta Prostate Cancer Research Initiative (APCaRI), which Kinnaird chairs. A total of 6,534 men who were diagnosed with prostate cancer between 2014 and 2023 were included, with 177 of them self-identifying as Black. The study showed that the Black men were just as likely to survive and remain metastasis-free as the general patient population.

In the United States and the United Kingdom, other studies have shown that men of African and Caribbean descent face double the lifetime risk of developing prostate cancer compared with Caucasian men, suggesting a biological causation.

However, those countries have two-tier or mainly private health-care systems, Kinnaird notes. The Alberta results from within a publicly funded health-care system indicate that these differences in the U.K. and U.S. may be more strongly influenced by socioeconomic factors such as racism, poverty and limited access to health care than by genetics, he says.

Both the American Urology Association and the European Urology Association recommend earlier screening for men of African ancestry and other high-risk populations, but the Canadian guidelines do not. Kinnaird would like to see that change.

Kinnaird points to previous research by his team showing that Indigenous men get fewer tests for prostate cancer and have worse outcomes than others . He suspects that may be due to poorer access to health care for rural Albertans in general, but further study is necessary.

"The crux of it is that if you can detect it at an early, localized, treatable stage, we have a cure rate of 95% or greater. But if you wait until the cancer metastasizes, then we currently do not have any cures available," he says. "When detected late, it is now a lethal disease."

Patrick Albers et al, Prostate Cancer Among Black Men in Canada, JAMA Network Open (2024). DOI: 10.1001/jamanetworkopen.2024.18475

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Full-life technologies granted fda fast track designation for 225ac-fl-020 for the treatment of metastatic castration-resistant prostate cancer.

HEIDELBERG, Germany , July 2, 2024 /PRNewswire/ -- Full-Life Technologies (Full-Life), a fully integrated global radiotherapeutics company, today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track Designation for 225 Ac-FL-020, the company's lead radiopharmaceutical, which targets prostate-specific membrane antigen (PSMA), for the treatment of metastatic castration-resistant prostate cancer (mCRPC).

The Fast Track program is designed to facilitate the development and regulatory review of novel potential therapies intended to treat serious conditions and fill an unmet need. This designation highlights the potential of 225 Ac-FL-020 to provide a novel therapeutic option for patients with mCRPC, a condition for which there are currently limited effective treatments.

"The FDA Fast Track Designation for 225 Ac-FL-020 underscores the critical need for innovative and effective treatments for mCRPC", said Steffen Heeger , M.D., M.Sc., Chief Medical Officer of Full-Life. "This designation will enable us to collaborate more closely with the FDA throughout the development process, potentially accelerating the availability of 225 Ac-FL-020 to patients."

225 Ac-FL-020 employs targeted alpha-radiotherapy designed to selectively attack cancer cells, reducing the damage to healthy tissues. In preclinical models, radiolabeled FL-020 displayed a very promising in vivo biodistribution profile, with high and sustained tumor uptake and fast systemic clearance. 225 Ac-FL-020 exhibited robust anti-tumor activity in LNCaP xenograft mice, with a favorable safety profile. Th e P hase I clinical trial will evaluate the safety, tolerability, and anti-tumor activity of 225 Ac-FL-020. In May 2024 , Full-Life received clearance of its Investigational New Drug (IND) Application from the FDA for clinical trials of 225 Ac-FL-020.

About 225 Ac-FL-020 225 Ac-FL-020 is a novel, potential best-in-class, next-generation PSMA-targeting radionuclide drug conjugate (RDC) that entered global Ph1 clinical studies in 2024. Its targeting vector, FL-020, was discovered using Full-Life's proprietary UniRDC™ platform, which enables significant improvement of drug uptake in the tumor while maintaining fast systemic clearance. In pre-clinical models, 225 Ac-FL-020 has demonstrated potent anti-tumor activity and a favorable safety profile.

About Full-Life Technologies Full-Life Technologies ("Full-Life") is a fully integrated global radiotherapeutics company with operations in Belgium , Germany , and China . We aim to own the entire value chain for radiopharmaceutical research & development, production & commercialization to deliver clinical impact for patients. The Company endeavors to tackle fundamental challenges affecting radiopharmaceuticals today by pioneering innovative research that will shape the treatments of tomorrow. We are comprised of a team of fast-moving entrepreneurs and seasoned scientists with a proven history of success in the life sciences, alongside radioisotope research and clinical development.

View original content: https://www.prnewswire.com/news-releases/full-life-technologies-granted-fda-fast-track-designation-for-225ac-fl-020-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-302186673.html

SOURCE Full-Life Technologies

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JSmol Viewer

Is there an opportunity to de-escalate treatments in selected patients with metastatic hormone-sensitive prostate cancer.

Simple Summary

1. introduction, 2. why intensify treatment in mhspc, 3. current management of mhspc, 3.1. adt+arpi, 3.2. adt+docetaxel+arpi, 3.3. radiotherapy to the primary tumour, 3.4. metastasis-directed therapy, 4. de-intensification of treatment: is there a reason to consider it, 5. the role of clinical and molecular biomarkers in decision making, 5.1. clinical biomarkers, 5.2. molecular biomarkers, 6. conclusions, author contributions, conflicts of interest.

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Share and Cite

Gómez-Aparicio, M.A.; López-Campos, F.; Buchser, D.; Lazo, A.; Willisch, P.; Ocanto, A.; Sargos, P.; Shelan, M.; Couñago, F. Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer? Cancers 2024 , 16 , 2331. https://doi.org/10.3390/cancers16132331

Gómez-Aparicio MA, López-Campos F, Buchser D, Lazo A, Willisch P, Ocanto A, Sargos P, Shelan M, Couñago F. Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer? Cancers . 2024; 16(13):2331. https://doi.org/10.3390/cancers16132331

Gómez-Aparicio, María Antonia, Fernando López-Campos, David Buchser, Antonio Lazo, Patricia Willisch, Abrahams Ocanto, Paul Sargos, Mohamed Shelan, and Felipe Couñago. 2024. "Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?" Cancers 16, no. 13: 2331. https://doi.org/10.3390/cancers16132331

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