Dr. Spratt began by discussing three clinical trials which evaluated the use of adjuvant radiotherapy in men who were felt to be at high risk of biochemical recurrence based on pathologic features (pT3 or R1, N0) following radical prostatectomy. In each trial, men received 60-64 Gy in the adjuvant setting. In each trial, biochemical progression free survival was improved in a statistically significant fashion over men who did not receive adjuvant XRT. It is likely that there are subgroups of men in whom adjuvant radiotherapy may improve rates of metastasis and overall survival, however, these subgroups of men cannot be easily defined currently.
He next discussed the current underutilization of adjuvant radiotherapy using data from the Michigan Urological Surgery Improvement Collaborative (MUSIC). Only 8% of patients who could potentially benefit from adjuvant radiotherapy received treatment. He highlighted the importance of determining a man's absolute risk of biochemical recurrence when determining who should undergo adjuvant radiotherapy. There is some data to suggest that the use of currently-available genomic profiling tests can potentially be helpful in guiding the use of adjuvant XRT.
Salvage radiotherapy was then discussed. Dr. Spratt highlighted the fact that there is no current level 1 evidence to demonstrate the benefit of salvage radiotherapy. As with adjuvant radiotherapy, there also appears to be underutilization of salvage radiotherapy in men with detectable and rising PSAs after radical prostatectomy. Data from MUSIC suggest only a 31% utilization of salvage XRT in men who would be candidates for treatment.
He then presented the data about the optimal timing of salvage radiotherapy. Many international guidelines recommend early salvage XRT (PSA <0.5), however only 1 in 6 men receive early salvage therapy. Studies from Abughaib et al and Tendulkar et al suggest that early salvage XRT leads to a decrease in the incidence of distant metastasis. Patients were stratified by their pre-salvage radiotherapy PSA values. Kaplan-Meier curves show that patients who undergo XRT with lower PSA values have a lower incidence of distant metastatic disease. This suggests that very early salvage radiotherapy (PSA <0.2) may be the most beneficial strategy. Ultra sensitive PSA assays may become useful in determining early biochemical recurrence so that patients can be referred for very early salvage XRT.
Next, he discussed adjuvant versus salvage XRT. It is important to note that there is currently no level 1 evidence to suggest that either approach is superior. A 2016 study from Buscariollo et al retrospectively compared patients who underwent adjuvant XRT for adverse pathologic features to men who underwent early salvage XRT (PSA <0.2) for biochemical recurrence. The men who underwent adjuvant therapy had 73% biochemical recurrence free survival versus 49% for men undergoing early salvage therapy after 10 years (p < 0.01). There are several trials ongoing currently which will compare adjuvant XRT to salvage XRT, including RADICALS-RT, TROG-RAVES, AND GETUG-17.
Finally, Dr. Spratt talked about the relative lack of data that currently exists to help guide the use of adjuvant ADT in men undergoing salvage radiotherapy. The RTOG 9601 and GETUG-AFU-16 trials have suggested a potential benefit of adjuvant ADT, particularly in men with a >7 year life expectancy and a PSA of >0.7
He concluded that the development of predictive biomarkers could help guide the decision for adjuvant or early salvage therapy in the future.
Presented by: Daniel Spratt, M.D. Assistant Professor, Vice Chair, Clinical Research Chair, Division of Genitourinary Clinical Research Chief, Genitourinary Radiotherapy Program Department of Radiation Oncology, University of Michigan.
Written by: Brian Kadow, MD, Fox Chase Cancer Center, Philadelphia, PA at the 18th Annual Meeting of the Society of Urologic Oncology, November 20-December 1, 2017 – Washington, DC