In reply to Egger et al.: Lack of benefit from adjuvant postoperative radiotherapy and issues raised about upfront management of high- and very-high-risk prostate cancer patients

Since 2013, based on a previous retrospective experience including 307 patients treated with ART or SRT, policy in our department was based on the concept that ART should be recommended for all patients with adverse prognostic factors, reserving SRT to patients with low‐risk baseline features. Recent data from literature seem to suggest that impact of ART in terms of survival outcomes may be limited and that some high‐risk patients undergoing radical prostatectomy (RP) may remain free from biochemical recurrence. However, this raises some questions regarding the upfront management of high‐risk patients (Surgery vs radical RT and neoadjuvant‐concomitant androgen deprivation therapy – ADT). No prospective evidence supports the superiority of one active management in prostate cancer patients, and all patients should be informed that no active treatment modality has shown superiority in terms of survival. RP is related to higher risk of erectile dysfunction (ED) and urinary incontinence if compared to radiotherapy, as suggested by prospective evidence.4 Thus, upfront RP should be carefully discussed, underlining the potential side effects and taking in consideration patients preferences. Considering the recent data from literature, multimodal treatment based on upfront RP followed by ART+/−ADT in patients with high‐risk features (positive margins, pT3a‐b or failure to reach an undetectable PSA after surgery) should not be considered a standard approach. Indeed, baseline local staging with magnetic resonance imaging (MRI) should prompt multidisciplinary team to avoid upfront surgery in all patients in whom extraprostatic extension, seminal vesicle invasion or positive surgical margins could lead to higher risk of biochemical relapse after RP, especially considering the evolving clinical landscape, in which ART should not be considered as a treatment intensification for all those patients with the above‐mentioned features. This is particularly true for patients with clinical suspicion of regional disease. Evidence for benefit of multimodal treatment is lower, and use of postoperative radiotherapy to increase loco‐regional control is debated. Furthermore, emerging imaging modalities may help to identify a significant percentage of de‐novo metastatic patients in whom radical intent of upfront surgery would be questionable. Conversely, use of radiotherapy on primary disease is supported for patients with low burden metastatic disease by results of the STAMPEDE trial. Positive margins, pT3a‐T3b stage or detectable PSA are not balanced by treatment intensification with postoperative treatment, and additional impact in terms of ED and urinary incontinence is probably unwarranted. These patients could be optimally managed with radical RT+ neoadjuvant/concomitant ADT, an equivalent treatment option in terms of oncological outcomes, with lower impact on long term toxicity and overall quality of life.