He started the talk by reminding the audience that radiotherapy is the only potential cure for patients with biochemical. The evidence of salvage radiotherapy is based on 3 main articles: Stish et al. (JCO 2016)1, Abugharib et al. (JUrol 2017)2, and Tendulkar et al. (JCO 2016)3. In all 3 studies, salvage radiation therapy (RT) was associated with distant metastasis-free survival – but, more importantly, the benefit was staggered based on PSA at the time of RT. The lower the PSA, the better the response. Hence, early salvage (PSA < 0.2) is recommended for patients with BCR. The main risk factors for progression after salvage RT are, on multiple studies, Gleason score 8-10, pT3b disease, and higher PSA prior to RT. * His main take-home message – refer to Radiation Oncology early for consideration of salvage RT.
Next, he addressed the role of hormone therapy as a radiosensitizer. In this topic, there are 2 main studies that highlight the importance of adding hormone therapy to RT. First is the RTOG 96-01 study, which tested RT vs. RT/bicalutamide. It identified a 4% OS benefit at 10 years and a 6% disease-specific survival benefit at 10 years. The GETUG-AFU 16 study, which randomized men to either RT or RT/goserelin identified a 50% reduction in progression-free survival at 8 years. * Based on these, salvage RT should be given with ADT (typically 6 months).
Next, he addressed the question of adjuvant vs. salvage RT. He discussed the recent paper by Hwang et al.4, which found that on retrospective evaluation, men treated with adjuvant RT had improved MFS at 10-15 years compared to men who underwent “early” SRT. However, he noted that in this study, men in the eSRT actually did not receive ADT and were treated when their median PSA was 0.3 – so it wasn’t even “early” salvage. Hence, he still believes early salvage is equivalent to adjuvant RT until better data can be provided.
Lastly, he briefly discussed his thoughts on PSMA PET scans and management of pN1 patients. With regards to PSMA PET scan, the evidence is somewhat controversial regarding its utility in planning for salvage RT, as it is only really positive when the PSA > 0.5 – at which point early salvage is too late. Hence, he doesn’t believe the utility of the PSMA PET for salvage RT decision making.
*He emphasized the importance to refer early to Radiation Oncology for consideration of RT – and not waiting until the PSA high enough to do a PSMA PET CT.
With regards to pN1 patients, data suggests that aggressive multimodal therapy is associated with relatively good prognosis – disease-specific survival on the order of 80-90%. The predictors of worse CSS were men with pT3b-4 disease & positive surgical margins or greater than 3-4 positive nodes. However, he made it clear that in patients with <3 noes and <= pT3a disease, whole pelvis radiation (with radiation of the nodal beds) is feasible with minimal (Grade 1-2) toxicity.
His ending was this flowchart of how he manages patients post-RP with BCR:
Presented by: Gert De Meerleer, MD, Ph.D., Universitair Ziekenhuis Leuven, Department of Radiation Oncology, Ghent, Belgium
Written by: Thenappan Chandrasekar, MD. Clinical Instructor, Thomas Jefferson University, Twitter: @tchandra_uromd, @TjuUrology, at the 16th Meeting of the European Section of Oncological Urology, #ESOU19, January 18-20, 2019, Prague, Czech Republic
References:
1. Stish et al. (2016). Improved Metastasis-Free and Survival Outcomes With Early Salvage Radiotherapy in Men With Detectable Prostate-Specific Antigen After Prostatectomy for Prostate Cancer. Journal of Clinical Oncology, 34, (32), 3864-3871. DOI: 10.1200/JCO.2016.68.3425.
2. Abugharib et al. (2016). Very Early Salvage Radiotherapy Improves Distant Metastasis-Free Survival. Journal of Urology, 197 (3 Pt 1):662-668. doi: 10.1016/j.juro.2016.08.106.
3. Tendulkar et al. (2016). Contemporary Update of a Multi-Institutional Predictive Nomogram for Salvage Radiotherapy After Radical Prostatectomy. Journal of Clinical Oncology, 34, (30) 3648-3654. DOI: 10.1200/JCO.2016.67.9647
4. Hwang et al. (2018). Comparison Between Adjuvant and Early-Salvage Postprostatectomy Radiotherapy for Prostate Cancer With Adverse Pathological Features. JAMA Oncology, 4(5):e175230. doi:10.1001/jamaoncol.2017.5230