ESTRO 2025 Congress report
By the ESTRO Urology Focus Group

The PEACE-V STORM trial addresses a critical clinical question in prostate cancer management: What is the optimal treatment strategy for patients with oligorecurrent nodal disease? This European multicentre phase-II randomised trial, which was initiated in 2018, has now yielded definitive results that can inform clinical practice in this challenging patient population.The presenter, Thomas Zilli, Oncology Institute of Southern Switzerland (IOSI), shared the final results of this important trial, which was designed to test the hypothesis that elective nodal pelvic radiation therapy (ENRT) would be superior to metastasis-directed therapy (MDT) in patients with oligorecurrent nodal prostate cancer. This hypothesis was based on previous studies such as the STOMP and ORIOLE trials, which had suggested that more comprehensive treatment approaches might offer benefits.

The STORM trial enrolled patients with up to five pelvic nodes that had been detected on PET imaging. They were randomised 1:1 to receive either MDT (stereotactic body radiotherapy (SBRT) of 3×10Gy to focal nodes, or salvage lymph-node dissection) or ENRT (45Gy in 25 fractions to the pelvic nodal regions with a simultaneous integrated boost to the detected nodes of up to 65Gy). In cases in which patients had undergone prior surgical lymph-node dissection, elective nodal irradiation was delivered at 45 Gy. All patients in both arms received androgen deprivation therapy (ADT) using luteinising hormone-releasing hormone agonists or antagonists for six months. Prostate bed radiotherapy was recommended for patients with high-risk features such as pT3 disease, Gleason score ≥8, or R1 resection margins.

With 196 randomised patients (97 in the MDT arm and 93 in the ENRT arm, whose results were analysable), the trial achieved a robust enrolment rate to test its hypothesis. The patient population was predominantly high-risk according to European Association of Urology guidelines; approximately 90% of patients showed rapid doubling of levels of prostate-specific antigen (PSA, <12 months) and high Gleason scores. Most patients (>80%) were staged using modern PET-CT imaging with use of prostate-specific membrane antigen (PSMA), and the majority had either one node (55% in the MDT arm, 62% in the ENRT arm) or two nodes (approximately 25% in both arms), with fewer than 20% having three to five nodes. It's noteworthy that concomitant radiotherapy to the prostate bed was delivered to only 25% of MDT patients compared with 43% of ENRT patients.

Analysis of the primary endpoint revealed that use of ENRT significantly improved metastasis-free survival at four years, with 76% of ENRT patients remaining metastasis-free compared with 63% in the MDT arm (hazard ratio 0.62, p=0.06). This 13 percentage point absolute benefit confirms the superiority of ENRT. Subgroup analyses indicated that patients who were restaged with PSMA PET-CT and who had baseline PSA levels of <1ng/ml derived the greatest benefit from ENRT.

Secondary endpoints similarly favoured the ENRT approach. Biochemical relapse-free survival at four years was significantly better with ENRT (57% vs. 41%, hazard ratio 0.62, p<0.05). Local-regional relapse-free survival showed an even more dramatic difference, with 85% control at four years in the ENRT arm versus only 62% in the MDT arm (hazard ratio 0.45, p<0.05). Analysis of relapse patterns revealed that MDT patients were much more likely to experience pelvic nodal recurrences (29% vs. 8%) and distant nodal metastases (M1a disease, 28% vs. 14%) compared with ENRT patients.

The ENRT approach also resulted in fewer subsequent treatments. Only 28% of ENRT patients required additional active treatment (either further MDT or ADT), compared with 52% of MDT patients. This translated to better ADT-free survival, with 77% of ENRT patients remaining free from further hormonal therapy at four years versus 60% of MDT patients (p<0.05).

Importantly, this efficacy benefit did not come at the cost of increased toxicity. After baseline correction, the genitourinary toxicity rate (grade ≥2) was comparable between the arms (28% for MDT vs. 31.5% for ENRT, not statistically significant). The gastrointestinal toxicity rate (grade ≥2) was similar and remarkably low in both arms (7.3% for MDT vs. 8.8% for ENRT). However, the addition of prostate bed irradiation significantly increased both genitourinary and gastrointestinal toxicity levels, though it prevented local recurrences effectively.

In the discussion after the presentation, Giulio Francolini characterised these findings as "practice-changing results", noting that ENRT "provided better clinical outcomes with comparable tolerability". He highlighted several important nuances regarding clinical implementation, including the need to discuss the risk-benefit ratio of prostate bed radiotherapy carefully with each patient. He also noted that although the results clearly establish ENRT as the standard-of-care for high-risk biochemical relapse with oligopelvic recurrence (90% of the trial population), MDT may still be a reasonable choice for low-risk biochemical relapse.

Giulio Francolini, Azienda Universitaria Ospedaliera Careggi, Italy,  also mentioned future research directions, including the potential for shortened hypofractionated regimens, possible extension of treatment fields to include para-aortic regions to address M1a relapses, and the integration of androgen-receptor-pathway inhibitors based on the EMBARK trial results. The optimal combination of local and systemic therapies in the evolving treatment landscape remains an active area of investigation.

In conclusion, the PEACE-V STORM trial establishes ENRT as the new standard-of-care for patients with oligorecurrent nodal prostate cancer, as it demonstrates significant improvements in metastasis-free survival, biochemical control, and local-regional control compared with MDT, all while maintaining excellent tolerability. These findings represent an important advance in the management of this challenging patient population.

Piet Ost
Radiation Oncologist
Iridium Network
ESTRO Urology Focus Group, Chair

 

Thomas Zilli

Department of Radiation Oncology

Oncology Institute of Southern Switzerland, EOC

Bellinzona, Switzerland
ESTRO Urology Focus Group, Core Expert

References

• Zilli T, et al. Final results of the PEACE-V STORM trial: Elective nodal radiotherapy versus metastasis-directed therapy for oligorecurrent nodal prostate cancer.
• Presentation Number: E25-4974.