Barcelona, Spain (UroToday.com) At the ESMO 2019 prostate cancer session, RADICALS – a phase III trial of adjuvant radiotherapy vs observation + salvage radiotherapy after radical prostatectomy – reported no benefit of adjuvant radiotherapy, and ARTISTIC – a prospective meta-analysis of RADICALS, RAVES, and GETUG-AFU 17 – reported a pooled hazard ratio also demonstrating no benefit to adjuvant radiotherapy. To discuss these two abstracts, Dr. Gert De Meerleer provided the radiation oncologist’s perspective.

Looking closer at the baseline characteristics for the patients included in RADICALS, Dr. De Meerleer noted that there were very few patients with Gleason 8-10 prostate cancer (17% in the observation + salvage radiotherapy arm and 16% in the adjuvant radiotherapy arm), as well as very few patients with seminal vesicle invasion (20% in the observation + salvage radiotherapy arm and 19% in the adjuvant radiotherapy arm). This trend is also noted in the ARTISTIC meta-analysis, where Gleason 8-10 prostate cancer rates were 9-17% and seminal vesicle invasion rates were 19-21%. He notes that in Belgium and perhaps other countries in the world, surgeons are operating on much higher risk prostate cancer leading to much higher rates of patients being considered for either adjuvant radiotherapy or early salvage therapy.

With regards to timing of early salvage radiotherapy, Dr. De Meerleer highlighted a study of 716 node-negative patients with undetectable postoperative PSA who experienced a PSA rise after RP, of which all patients received early salvage radiotherapy (defined as local radiation to the prostate and seminal vesicle bed, delivered at PSA ≤ 0.5 ng/ml) [1]. At 5 years after early salvage radiotherapy, BCR-free survival rate was 82%; multivariable Cox regression analysis demonstrated that pre- early salvage radiotherapy PSA level was significantly associated with BCR after early salvage radiotherapy (HR 4.89, 95% CI 1.40-22.9). When patients were stratified according to the number of risk factors at final pathology, patients with at least two pathologic risk factors (ie. Gleason 8-10 or seminal vesicle invasion) showed an increased risk of 5-year BCR as high as 10% per 0.1 ng/ml of PSA level compared with only 1.5% in patients with one or no pathologic risk factors.

Ultimately, Dr. De Meerleer notes that we need to continue to improve. One way is to give concomitant hormone therapy with radiotherapy for biochemically recurrent prostate cancer. GETUG-AFU 16 enrolled 743 men with stage pT2, pT3, or pT4a (bladder neck involvement only) in patients who had rising PSA of 0.2 to less than 2.0 μg/L following radical prostatectomy [2]. These patients were randomized to standard salvage radiotherapy or radiotherapy plus short-term androgen suppression using 10.8 mg goserelin. Patients assigned to radiotherapy plus goserelin were significantly more likely than patients in the radiotherapy alone group to be free of biochemical progression or clinical progression at 5 years (80% vs 62%; HR 0.50, 95% CI 0.38-0.66).

An additional point of issue with RADICALS according to Dr. De Meerleer is the lack of information on nodal dissection: thus, we have no delineation between pN0 and pNx patients. RTOG 0534 showed a significant difference in freedom from progression at 5-years for patients undergoing pelvic radiotherapy + prostate bed radiotherapy + pelvic lymphadenectomy at the time of radical prostatectomy compared to those without lymphadenectomy.

Dr. De Meerleer concluded with several take-home messages from his summary of RADICALS and the ARTISTIC meta-analysis:

  • A cure is the aim and radiotherapy is a keystone in the management of these patients
  • Salvage radiotherapy is probably the modality of choice, but the key is early salvage radiotherapy
  • It is important to not miseducate ourselves or our colleagues
  • Remember the patient characteristics of those enrolled in RADICALS – these were not the typical high-risk patients we may encounter
  • Based on GETUG-AFU 16, ADT may be beneficial when administering radiotherapy after radical prostatectomy

Presented by: Gert De Meerleer, MD, PhD, Department of Radiation Oncology, University Hospitals Leuven, Leuven, Belgium

Written by: Zachary Klaassen, MD, MSc – Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia Twitter: @zklaassen_md at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept – 1 Oct 2019 in Barcelona, Spain 

References:
1. Fossati N, Karnes RJ, Cozzarini C, et al. Assessing the Optimal Timing for Early Salvage Radiation Therapy in Patients with Prostate-specific Antigen Rise After Radical Prostatectomy. Eur Urol 2016 Apr;69(4):728-733.
2. Carrie C, Hasbini A, de Laroche G, et al. Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): A randomized, multicentre, open-label phase 3 trial. Lancet Oncol 2016;17(6):747-756.

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