Barcelona, Spain ( Men who undergo surgery as definitive therapy for their localized prostate cancer generally only receive subsequent radiation therapy if their surgical pathology shows certain adverse pathologic features (adjuvant radiotherapy or aRT) or if they experience biochemical recurrence (salvage radiotherapy or eSRT). Given conflicting clinical trial data that utilized outdated definitions and assays for biochemical recurrence, three trials are underway to compare aRT and eSRT.  In this session, Dr. Gert De Meerleer, a radiation oncologist, discussed the prior two presentations consisting of event free and biochemical progression free survival data from both RADICALS-RT and a prospective meta-analysis incorporating RADICALS-RT and two other randomized trials by the ARTISTIC group. This data, in summary, show no statistically significant difference between aRT and eSRT with regards to the early patient outcomes of biochemical recurrence or event free survival.

Dr. Meerleer identified several caveats that may limit the generalizability of the presented trial data. First, high-risk localized disease patients were under-represented in these cohorts, yet many of these high-risk patients across the world do receive surgical therapy as primary treatment. These patients have the highest need for therapies that optimize their chance at cure, as they have the highest risk of developing recurrent and life-threatening progressive disease. Second, only a minority proportion of patients in these trials received concurrent hormonal therapy. Given (1) the known benefit of concurrent androgen deprivation therapy (ADT) with radiotherapy in the primary definitive treatment setting, and (2) updated GETUG-AFU 16 data from ASCO 2019 showing improved 10-year metastasis free survival rates with short course ADT + radiotherapy in the salvage setting, it is possible that the summarized trials here do not represent optimal therapy regardless of adjuvant or salvage context. Third, 35% of patients in the RADICALS trial received only 52.5 Gy to the prostatic bed. This dose is lower than the regimens being compared by the ongoing SAKK 9/10 trials comparing 64 Gy to 70 Gy in the salvage setting. Fourth, there is no information on nodal status in these trials, which may affect the most appropriate way to design radiation fields in patients receiving radiotherapy.

Despite these caveats, these trials provide an important study platform to understand the optimal method for increasing the chance of cure after surgery for men with localized prostate cancer. The data suggest that adjuvant radiotherapy and early salvage radiotherapy are equal at least with regards to event free survival (mainly biochemical recurrence) for the type of patient included in these analyses: predominantly Gleason 7, pT3 localized prostate cancer. As the majority of men in the salvage therapy arms have not received radiotherapy, there is an additional benefit of avoiding unnecessary treatment and its associated toxicities. Future subgroup data from the ARTISTIC meta-analysis may help clarify which patients benefit from radiotherapy in the adjuvant setting. Other trial data will help further define the role of concurrent hormonal therapy and its duration, in men who require radiotherapy.

In summary, the current data suggest that immediate radiotherapy is not required, waiting too long is not good enough, but an early salvage approach to cure men with localized prostate cancer may be just right.

Presented by: Gert De Meerleer, MD, PhD, Radiation Oncologist, Universitair Ziekenhuis Leuven, Leuven, Belgium

Written by: Alok Tewari, MD, PhD, Medical Oncology Fellow at the Dana-Farber Cancer Institute, at the 2019 European Society for Medical Oncology annual meeting, ESMO 2019 #ESMO19, 27 Sept – 1 Oct 2019 in Barcelona, Spain