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Top Line: Can a genomic classifier improve our decision-making for men receiving salvage post-prostatectomy radiation?

The Study: SAKK 09/10 was a randomized trial that tested dose escalation for salvage, post-prostatectomy radiation. It found that escalating dose from 64Gy in 32 fractions to 70Gy in 35 fractions did not improve freedom from biochemical progression. Importantly, patients received only prostate fossa radiation with on ADT and no pelvic lymph node coverage. Thus, SAKK 09/10 provides an opportunity to evaluate factors that identify which patients benefit from treatment intensification. In this study, prostatectomy specimens from 226 SAKK 09/10 participants were used to validate the prognostic value of the Decipher genomic classifier (GC). GC scores were categorized as low (58.9%), intermediate (15.9%), and high (25.2%). As a continuous variable, increasing GC was associated with increasing risk of biochemical progression after salvage RT. Those with a high GC had a significantly lower rate of freedom from biochemical progression (FFBP) at 5 years than those with low/intermediate GC (45% v 71%). Patients with high GC were also more likely to experience clinical progression and require androgen deprivation therapy. So, how could Decipher impact your practice? The authors suggest that if the GC were used to identify patients who do or do not benefit from treatment intensification with ADT and nodal radiation, the rate of patients who are “overtreated” could be reduced by more than half. Furthermore, the GC could inform the decision when to initiate salvage RT based on PSA. Among those with high GC, the rate of FFBP falls by a whopping 65% when waiting until the PSA is >0.2 to deliver salvage RT compared to a (perhaps) more tolerable 11% for low GC. In fact, the rate of biochemical progression was 90% among those with a high GC who received late salvage RT (PSA>0.5).

TBL: In the SAKK 09/10 trial, the Decipher genomic classifier was associated with risk of biochemical progression, and it identified men at high risk who may benefit from very early salvage radiation and further treatment intensification with ADT and pelvic nodal radiation. | Dal Pra, Ann Oncol 2022