The addition of pelvic lymph node treatment to prostate bed salvage radiotherapy

We read the results of the SPPORT trial with great interest.1Pollack A Karrison TG Balogh AG et al.The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.Lancet. 2022; 399: 1886-1901Summary Full Text Full Text PDF PubMed Google Scholar Patients were randomly assigned to salvage prostate bed radiotherapy (PBRT), PBRT plus short-term androgen deprivation therapy (ADT), or PBRT plus short-term ADT plus pelvic lymph node radiotherapy (PLNRT). With a median follow-up of 8·2 years, the study showed a benefit in terms of 5-year freedom from progression rates of adding short-term ADT and PLNRT to PBRT. According to guidelines from the American Urological Association (AUA), the biochemical recurrence of prostate cancer after surgery is defined as a detectable serum prostate-specific antigen (PSA) concentration of 0·2 ng/mL or higher, which is later confirmed by a second measurement of 0·2 ng/mL or higher.2Cookson MS Aus G Burnett AL et al.Variation in the definition of biochemical recurrence in patients treated for localized prostate cancer: the American Urological Association Prostate Guidelines for Localized Prostate Cancer Update Panel report and recommendations for a standard in the reporting of surgical outcomes.J Urol. 2007; 177: 540-545Crossref PubMed Scopus (586) Google Scholar According to the inclusion criteria,1Pollack A Karrison TG Balogh AG et al.The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.Lancet. 2022; 399: 1886-1901Summary Full Text Full Text PDF PubMed Google Scholar patients with PSA concentrations of 0·1–2·0 ng/mL were included. However, the freedom from progression endpoint was driven by the Phoenix definition, which is used worldwide for follow-up after definitive radiotherapy. We are interested to know the reason for using the Phoenix definition, as most of the world uses the AUA definition of biochemical recurrence in the postoperative setting. Two previous prospective studies have shown a benefit in terms of recurrence-free survival when ADT is added to PBRT.3Carrie C Magné N Burban-Provost P et al.Short-term androgen deprivation therapy combined with radiotherapy as salvage treatment after radical prostatectomy for prostate cancer (GETUG-AFU 16): a 112-month follow-up of a phase 3, randomised trial.Lancet Oncol. 2019; 20: 1740-1749Summary Full Text Full Text PDF PubMed Scopus (90) Google Scholar, 4Shipley WU Seiferheld W Lukka HR et al.Radiation with or without antiandrogen therapy in recurrent prostate cancer.N Engl J Med. 2017; 376: 417-428Crossref PubMed Scopus (368) Google Scholar In SPPORT, the addition of short-term ADT to PBRT also improved freedom from progression outcomes, as might be expected; however, the rationale underlying the benefit of PLNRT is not clear. The role of PLNRT as salvage therapy is still controversial for patients without nodal involvement. At least ten lymph nodes must be removed to establish accurate staging by lymph node dissection.5Kazzazi A Djavan B Current status of pelvic lymph node dissection in prostate cancer: the New York PLND nomogram.Can J Urol. 2011; 18: 5585-5591PubMed Google Scholar However, only a median of six lymph nodes was removed,1Pollack A Karrison TG Balogh AG et al.The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial.Lancet. 2022; 399: 1886-1901Summary Full Text Full Text PDF PubMed Google Scholar which is presumably insufficient. PLNRT could have benefitted patients with undissected occult lymphatic metastases. On the basis of these results, the application of PLNRT—which is more toxic than PBRT—might not be appropriate in patients without nodal involvement. Could the positive effect be related to PLNRT possibly compensating for inadequate lymph node dissection? Additionally, for patients with intermediate-risk prostate cancer who receive definitive radiotherapy, ADT is suggested for those classified in the unfavourable group but not for those classified in the favourable group. From this perspective, we think that a personalised treatment approach that considers the Gleason score and the PSA concentration at recurrence is important in the decision to apply ADT and PLNRT. In the treatment of prostate cancer, it would be logical to include groundbreaking metabolic imaging methods in the risk stratification of patients. In conclusion, although the results of SPPORT are valuable and thought-provoking, clarification of the aforementioned issues would be helpful to better understand the implications of the findings. We declare no competing interests.