The optimal management strategy for high-risk prostate cancer remains an area of active debate. This analysis pooled patient-level data from two major randomized phase III trials- RTOG 0521 and CALGB 9020, to compare outcomes between radiation-based and surgery-based treatment paradigms.

Patients on RTOG 0521 received radiotherapy with 24 months of ADT and were randomized to the addition of six cycles of adjuvant docetaxel, whereas patients on CALGB 90203 underwent radical prostatectomy and were randomized to six cycles of neoadjuvant docetaxel plus 18–24 weeks of ADT.

 The primary endpoint was the cumulative incidence of distant metastasis (DM), analyzed with death as a competing risk. Across the 1,290 aggregated patients, the CALGB 90203 (surgical) population was younger and had more favorable baseline prognostic features compared with the RTOG 0521 (radiotherapy-based) cohort. Despite this, the incidence of distant metastasis was significantly lower among patients treated with radiotherapy and long-term ADT: 15% vs 22% at 8 years. No significant difference was observed in the rate of death after development of distant metastasis between the two treatment strategies.

Authors concluded significantly lower incidence of distant metastasis with a radiotherapy-based approach than a surgical (radical prostatectomy) based treatment strategy.

Reference (Pub-Med Link):  Roy S, Sun Y, Eastham JA, et al. Radiotherapy- versus surgery-based treatment strategy in high-risk prostate cancer. Eur Urol Oncol 2025. https://doi.org/10.1016/j.euo.2025.06.009

Key Institution: Brigham and Women’s Hospital, Dana-Farber Cancer Institute, Multi-institutional

Keywords: Prostate cancer

Clinical cohort study that sought to develop and validate a multimodal artificial intelligence (MMAI)-derived predictive biomarker to predict the benefit of long-term ADT on distant metastasis (DM) in men with high-risk prostate cancer. The MMAI was trained for long-term vs short-term ADT using pretreatment digital prostate biopsy images and clinical data like age, PSA, Gleason, and T stage from six NRG Oncology phase III trials.  The MMAI was validated on a seventh trial, RTOG 9202 (N= 1192), which randomly assigned men to RT+ST-ADT vs RT+LT-ADT and showed significant reduction in distant mets with 28 months vs 4 months of ADT. A significant predictive interaction was observed with the digital biomarker for DM, where MMAI biomarker-positive men, 66%, had reduced DM with LT-ADT vs ST-ADT, whereas no treatment benefit was observed for MMAI biomarker-negative men. The estimated 15-year DM risk difference between RT+LT-ADT and RT+ST-ADT was 14% in MMAI biomarker-positive men and 0% in MMAI biomarker-negative men. Of note, the biomarker was also prognostic for DM, irrespective of treatment. It is an interesting new tool to help in management decisions for patients with HRPC. This, as well as the decipher genomic assay test, will be interesting to follow in the coming years to see how it evolves practice.   

Reference (Pub-Med Link):   Armstrong AJ, Liu VYT, Selvaraju RR, et al. Development and validation of an artificial intelligence digital pathology biomarker to predict benefit of long-term hormonal therapy and radiotherapy in men with high-risk prostate cancer across multiple phase iii trials. J Clin Oncol 2025;43:3494-3504. https://doi.org/10.1200/jco.24.00365

Key Institution: Duke University Medical Center, Multi-institutional

Keywords: Prostate Cancer

The PEACE-1 phase 3 trial investigated whether adding radiotherapy (74 Gy) to current treatments improves outcomes for metastatic prostate cancer patients. 1,173 patients were enrolled in European hospitals. The study compared standard care (androgen-deprivation therapy with/without docetaxel) alone or combined with abiraterone, radiotherapy, or both. In patients with low-volume disease, adding radiotherapy to abiraterone plus standard care significantly improved progression-free survival from 4.4 to 7.5 years (HR 0.65); this benefit wasn't seen without abiraterone. There was no significant improvement in overall survival (6.9 vs 7.5 years, HR 0.98). The overall rate of severe adverse events did not differ with the addition of radiotherapy, but severe genitourinary complications were decreased with radiotherapy. The combination could become a component of standard of care in patients with both high-volume and low-volume de novo metastatic castration-sensitive prostate cancer.

Reference (Pub-Med Link): Bossi A, Foulon S, Maldonado X, et al. Efficacy and safety of prostate radiotherapy in de novo metastatic castration-sensitive prostate cancer (peace-1): A multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet 2024;404:2065-2076. https://doi.org/10.1016/s0140-6736(24)01865-8

Key Institution: Institut Gustave Roussy, Multi-institutional

Keywords: Prostate Cancer

This study used tissue collected from NRG Oncology/RTOG 01-26, a randomized phase 3 trial of men with intermediate-risk prostate cancer who received either 70.2 Gy or 79.2 Gy of radiation therapy without androgen deprivation therapy. Tissues were assigned a genomic classifier according to the Decipher test. Of 1,532 participants in the trial, 215 had archived tissues with sufficient sample volume and passed a quality control assay. In the multivariable model, Decipher score was prognostic for disease progression, biochemical failure, distant metastasis, and prostate cancer-specific mortality. When patients were stratified according to existing Decipher score thresholds for low-, intermediate-, and high-risk groups, the high-risk group were found to be 12% more likely to develop a distant metastasis at 10 years. In an interaction analysis, dose escalation was associated with a significant reduction in distant metastasis in patients with intermediate- and high-risk Decipher classification. In conclusion, the Decipher score tracked clinically important outcomes in these intermediate-risk prostate cancer patients.

Reference (Pub-Med Link): Spratt et al. (2023). Spratt DE, Liu VYT, Michalski J, et al. Genomic classifier performance in intermediate-risk prostate cancer: Results from nrg oncology/rtog 0126 randomized phase 3 trial. Int J Radiat Oncol Biol Phys 2023;117:370-377.https://doi.org/10.1016/j.ijrobp.2023.04.010

Key Institution: Memorial Sloan Kettering Cancer Center, Multi-institutional

Keywords: Prostate Cancer

The ORIOLE trial phase 2 trial was conducted across 3 US institutions. The trial included 54 patients with recurrent hormone-sensitive prostate cancer and 1 to 3 metastases detectable by conventional imaging who had not received ADT within 6months of enrollment or 3 or more years total. The patients were randomized to observation vs. SABR for the metastatic sites. The results showed that 7 out of 36 patients (19%) receiving SABR and 11 of 18 patients (61%) undergoing observation experienced disease progression at 6 months (p=0.005). Treatment with SABR improved median progression-free survival (not received vs. 5.8 mon; HR 0.30; 95% CI0.11-0.81, p=0.002). In conclusion, treatment with SABR for oligometastatic prostate cancer improved outcomes.

(Open Access)

Reference (PubMed Link): Phillips R, Shi WY, Deek M, et al. Outcomes of observation vs stereotactic ablative radiation for oligometastatic prostate cancer: The oriole phase 2 randomized clinical trial. JAMA Oncol 2020;6:650-9.

Key Institution: Multi-Institutional (US)
Keywords: Oligometastatic prostate cancer, SABR