Three prospective randomised trials reported discordant findings regarding the impact of adjuvant radiation therapy (aRT) versus observation for metastasis-free survival (MFS) and overall survival (OS) among patients with pT3N0 prostate cancer treated with radical prostatectomy (RP). None of these trials systematically included patients who underwent early salvage radiation therapy (esRT).
To test the hypothesis that aRT was associated with better cancer control and survival compared with observation followed by esRT.
Using a multi-institutional cohort from seven tertiary referral centres, we retrospectively identified 510 pT3pN0 patients with undetectable prostate-specific antigen (PSA) after RP between 1996 and 2009. Patients were stratified into two groups: aRT (group 1) versus observation followed by esRT in case of PSA relapse (group 2). Specifically, esRT was administered at a PSA level ≤0.5ng/ml.
We compared aRT versus observation followed by esRT.
The evaluated outcomes were MFS and OS. Multivariable Cox regression analyses tested the association between groups (aRT vs observation followed by esRT) and oncologic outcomes. Covariates consisted of pathologic stage (pT3a vs pT3b or higher), pathologic Gleason score (≤6, 7, or ≥8), surgical margin status (negative vs positive), and year of surgery. An interaction with groups and baseline patient risk was tested for the hypothesis that the impact of aRT versus observation followed by esRT was different by pathologic characteristics. The nonparametric curve fitting method was used to explore graphically the relationship between MFS and OS at 8 yr and baseline patient risk (derived from the multivariable analysis).
Overall, 243 patients (48%) underwent aRT, and 267 (52%) underwent initial observation. Within the latter group, 141 patients experienced PSA relapse and received esRT. Median follow-up after RP was 94 mo (interquartile range [IQR]: 53-126) and 92 mo (IQR: 70-136), respectively (p=0.2). MFS (92% vs 91%; p=0.9) and OS (89% vs 92%; p=0.9) at 8 yr after surgery were not significantly different between the two groups. These results were confirmed in multivariable analysis, in which observation followed by esRT was not associated with a significantly higher risk of distant metastasis (hazard ratio [HR]: 1.35; p=0.4) and overall mortality (HR: 1.39; p=0.4) compared with aRT. Using the nonparametric curve fitting method, a comparable proportion of MFS and OS at 8 yr among groups was observed regardless of pathologic cancer features (p=0.9 and p=0.7, respectively). Limitations consisted of the retrospective nature of the study and the relatively small size of the patient population.
At long-term follow-up, no significant differences between aRT and esRT were observed for MFS and OS. Our study, although based on retrospective data, suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT.
At long-term follow-up, no significant differences in terms of distant metastasis and mortality were observed between immediate postoperative adjuvant radiation therapy (aRT) and initial observation followed by early salvage radiation therapy (esRT) in case of prostate-specific antigen relapse. Our study suggests that esRT does not compromise cancer control and potentially reduces overtreatment associated with aRT.
European urology. 2016 Jul 30 [Epub ahead of print]
Nicola Fossati, R Jeffrey Karnes, Stephen A Boorjian, Marco Moschini, Alessandro Morlacco, Alberto Bossi, Thomas Seisen, Cesare Cozzarini, Claudio Fiorino, Barbara Noris Chiorda, Giorgio Gandaglia, Paolo Dell'Oglio, Steven Joniau, Lorenzo Tosco, Shahrokh Shariat, Gregor Goldner, Wolfgang Hinkelbein, Detlef Bartkowiak, Karin Haustermans, Bertrand Tombal, Francesco Montorsi, Hein Van Poppel, Thomas Wiegel, Alberto Briganti
Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy. Electronic address: ., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Urology, Mayo Clinic, Rochester, MN, USA., Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France., Department of Radiation Oncology, Gustave Roussy Institute, Villejuif, France., Department of Radiotherapy; IRCCS Ospedale San Raffaele, Milan, Italy., Department of Radiotherapy; IRCCS Ospedale San Raffaele, Milan, Italy., Department of Radiotherapy; IRCCS Ospedale San Raffaele, Milan, Italy., Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy., Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy., University Hospitals Leuven, Department of Urology, Leuven, Belgium., University Hospitals Leuven, Department of Urology, Leuven, Belgium., Department of Urology, Comprehensive Cancer Centre, Medical University of Vienna, Vienna General Hospital, Vienna, Austria., Department of Radiation Oncology, Medical University of Vienna, Vienna, Austria., Department of Radiation Oncology, Charité Universitätsmedizin, Campus Benjamin Franklin, Berlin, Germany., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany., University Hospitals Leuven, Department of Radiotherapy, Leuven, Belgium., Department of Urology, Université Catholique de Louvain, Brussels, Belgium., Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy., University Hospitals Leuven, Department of Urology, Leuven, Belgium., Department of Radiation Oncology, University Hospital Ulm, Ulm, Germany., Division of Oncology/Unit of Urology; URI; IRCCS Ospedale San Raffaele, Milan, Italy.