Chris Parker

Very much agree with you, Tony. For DASL Very High Risk N0 patients, the MFS-CI benefit is substantial and very robust (and a surrogate for OS). In addition to a group more enriched in Gleason 9-10 than Enzarad, our patients were enrolled in era replete with PSMA PET. How does that impact the enrolled group (even though it was not formally included in eligibility)? There are two putatively localized settings where pts may not experience a significant MFS benefit from fixed duration ARPI intensification: 1) localized lower risk disease where metastatic potential is constrained and 2) localized by conventional imaging disease where PSMA PET reveals already extant mets. In the former, the metastatic cat may never get out of the bag; in the latter, it already is. In the DASL era, a patient with CI neg/PSMA PET pos disease probably wasn’t enrolled. Investigators might not have viewed the arms in equipoise in that setting. They may have thought such patients needed ARPI intensification as SOC for OS purposes. We thus removed a patient population unlikely to realize an MFS benefit, since they already had Mets. This, in combination with enrolling higher grade gleasons, really enriched for the N0 population most likely to benefit. That’s why I would argue that in our PSMA PET era, DASL should have controlling weight in decision making regarding adding an ARPI in the N0 setting. And for the RadOncs out there, with its favorable side effect profile, you might feel more comfortable take the initiative on prescribing Daro. #radonc