Metastases after early vs. delayed salvage radiation

Until we have the results of randomized clinical trials on the relative efficacy of early salvage radiation, we have to look for other clues to inform the timing of that decision. Adjuvant radiation carries a high risk of overtreatment, whereas delayed salvage may preclude the window of opportunity during which salvage radiation might have been curative.

Den et al. posted the outcomes of their investigative analysis at the ASCO Genitourinary Conference (Abstract 12). Data on 422 patients treated at 4 institutions were retrospectively analyzed. All had adverse pathology (either stage T3 or positive margins) after RP. Patients were arbitrarily divided according to their PSA after surgery at the time they received radiation:

• ·      <0.2 ng/ml – “adjuvant RT” (111 patients)
• ·      >0.2 but <0.5 ng/ml – “early salvage RT” (70 patients)
• ·      >0.5 ng/ml – “delayed salvage RT” (83 patients)
• ·      No radiation received (157 patients)

CAPRA-S scores and Decipher genomic classifier scores were found to independently predict risk of metastatic progression. Adjusting for those scores:

• ·      Delayed salvage RT increased risk of metastases by 4.3 times over adjuvant RT
• ·      No radiation increased risk of metastases by 5.4 times over adjuvant RT
• ·      Early salvage and adjuvant RT had about the same risk of metastases
• ·      Men with low CAPRA-S and Decipher scores had low risk of metastases
• ·      Men with high CAPRA-S and Decipher scores benefit from adjuvant RT, but had high rates of metastases nonetheless.

This study once again underscores the importance of early salvage radiation for curative therapy after failed surgery when there is adverse pathology. They didn’t investigate the use of ultrasensitive PSA to determine what the lowest level that avoids overtreatment might be. Adverse pathology and PSA are important to consider, but other clinical/genomic factors can contribute to the decision-making process as well. Low Decipher scores can help rule out those cancers that are unlikely to metastasize in the next 5-10 years. However, it is less useful at indicating those cancers that will metastasize.  And there are no good tests for determining if the cancer is already systemic and micrometastatic, in which case salvage radiation would be futile. This remains a challenging situation for discussion between the patient and radiation oncologist.