ESTRO 2026 congress report | Interdisciplinary track I: Proffered Papers Session
Report by the ESTRO Urology Focus Group

For decades, radiation oncologists have debated whether elective pelvic nodal irradiation should be routinely incorporated into the treatment of patients with very high-risk localised prostate cancer. While occult nodal micrometastases are thought to contribute to disease recurrence and metastatic progression, convincing evidence that prophylactic pelvic radiotherapy improves long-term outcomes has remained elusive.

At ESTRO 2026, Prof. Pierre Blanchard, France, Principal Investigator, presented the mature results of the PEACE-2 phase III randomised trial, providing one of the longest follow-ups available to address this important clinical question.

PEACE-2 enrolled patients with conventionally node-negative but very high-risk localised prostate cancer, a population characterised by a substantial risk of harbouring microscopic nodal disease despite negative imaging. The majority of patients (82%) fulfilled the STAMPEDE definition of very high-risk disease, while nearly 40% had an estimated nodal involvement risk exceeding 35% according to the Roach formula. Although next-generation imaging was not routinely available at the time the trial was designed, choline PET/CT was used in approximately 18% of patients.

The study employed a 2×2 factorial design evaluating the addition of pelvic radiotherapy and Cabazitaxel to standard treatment. As no interaction was observed between the two interventions, outcomes were analysed according to radiotherapy field allocation.

After a remarkable median follow-up of more than seven years (87 months), the results painted a nuanced picture. Elective pelvic irradiation was associated with a trend towards improved clinical progression-free survival, reducing the risk of clinical progression by approximately 19% (HR 0.81, 95% CI 0.63–1.03; p=0.088). At seven years, clinical progression-free survival reached 67.1% with pelvic radiotherapy compared with 62.9% in patients treated to the prostate alone.

However, the apparent gain in disease control did not translate into improvements in the endpoints that matter most to patients. No improvements were observed for biochemical progression-free survival (HR 0.84), metastasis-free survival (HR 0.90), cancer-specific survival (HR 0.95), or overall survival (HR 1.21). Five-year overall survival rates were excellent and nearly identical between treatment groups, reaching 91% and 92%, respectively.

Equally noteworthy was the safety profile. Despite concerns that larger treatment volumes could increase toxicity, pelvic irradiation was delivered without a significant excess of late adverse events, highlighting the ability of modern radiotherapy techniques to safely treat nodal volumes in the postop setting or in case of N1 disease.

During his presentation, Prof. Blanchard emphasised that the findings should be interpreted in the context of rapidly evolving imaging technologies and systemic treatment intensification strategies. While elective pelvic irradiation appeared to delay clinical progression modestly, the study provides no evidence that this approach alters the natural history of the disease by reducing metastatic spread or improving survival.

The PEACE-2 findings are particularly noteworthy when viewed alongside the companion analysis evaluating treatment intensification with Cabazitaxel, presented at ASCO GU 2026. Despite more than seven years of follow-up, Cabazitaxel failed to improve clinical progression-free survival, metastasis-free survival, or overall survival and was associated with increased toxicity. Taken together, these analyses suggest that neither elective pelvic irradiation nor chemotherapy intensification substantially improves long-term outcomes in patients with conventionally staged very high-risk localised prostate cancer.

Perhaps the most thought-provoking message from PEACE-2 is not the lack of benefit from either intervention, but rather the unexpectedly favourable outcomes observed across all treatment arms. Nearly 90% of patients were alive nine years after treatment, despite fulfilling contemporary definitions of very high-risk disease. These excellent long-term results raise important questions about current risk stratification and whether patients classified as “very high-risk” in the conventional imaging era truly represent the population most likely to benefit from treatment intensification.

The PEACE-2 trial, therefore, adds an important piece to the complex puzzle of pelvic nodal treatment in prostate cancer. Although elective pelvic radiotherapy remains biologically appealing and can be delivered safely with modern techniques, its routine use in conventionally node-negative, very high-risk disease cannot be justified on the basis of improved metastasis-free or overall survival. Future studies incorporating PSMA PET staging and contemporary systemic therapies will be crucial to identify the patients most likely to benefit from nodal irradiation.

Take-home message: After more than seven years of follow-up, PEACE-2 demonstrated a borderline improvement in clinical progression-free survival with elective pelvic radiotherapy, but no significant benefit in metastasis-free survival, cancer-specific survival, or overall survival. More importantly, the study highlights the excellent outcomes achieved with contemporary radiotherapy and long-term androgen deprivation therapy, while underscoring the need for more precise identification of patients who truly require treatment intensification.

 

Prof Thomas ZILLI

Department of Radiation Oncology

Oncology Institute of Southern Switzerland, EOC

Bellinzona, Switzerland
ESTRO Urology Focus Group Core Expert

 

 

 

Reference

¹ Pierre Blanchard, Stéphanie Foulon, Xavier Artignan et al. Pelvic radiotherapy in patients with very high-risk localized prostate cancer: results of the PEACE 2 phase III randomized trial.

Presentation Number: 5520