Standard of treatment for APC is adding AAP to ADT (metastatic, M1 & high-risk non-metastatic, M0). For patients (pt) initiating ADT +/- AAP, researchers evaluated transcriptome signatures as prognostic & predictive indicators.
On tumor index, core mRNA from pt randomly assigned 1:1 ADT:ADT+AAP in STAMPEDE, a clinical test (Decipher, Veracyte, San Diego) was used to do whole transcriptome profiling. The trial monitoring panels authorized a planned statistical analysis that was detailed in advance. Age, AAP (+/-), WHO PS, pre-ADT PSA, NSAID/aspirin usage, Gleason score, and disease burden (M0N0 vs M0N1 vs M1 low volume vs M1 high volume) were all included as factors in the Cox models that were fitted. Decipher genomic classifier (GC, continuous) for prognosis and AR-activity (AR-A, average vs. low) for prediction were the primary analyses. AAP study ended with a follow-up in November 2021.
Of the 1,917 patients (full trial cohort, FTC) enrolled between November 2011 and January 2014, 1,824 gave their consent for tumor investigation; 1,298 (71%) were centrally evaluated; 974 (75%) provided transcriptomes, and 781 (80%) passed quality control. About 50% of the 781 were M1 vs to 52% of the FTC; all clinical characteristics were evenly distributed. NInety-four months were the median follow-up (IQR: 84 – 97). APC (per 0.1 increase, M1 OS, HR [95% CI] 1.17 [1.09 – 1.26], P<0.001), and M0 MFS (HR 1.20 [1.09 – 1.31], P<0.001), all showed that GC was significantly predictive. Interaction HR 0.86 [0.56 – 1.33], P=0.5), which indicated that AR-A did not interact with AAP. Secondary analyses revealed that AAP had a consistent impact on PAM50, PSC, and GC, and that low AR-A patients had worse outcomes (M1, OS HR: 1.30 [0.99 – 1.70], P=0.06; M0, MFS HR: 1.56 [1.08 – 2.27], P=0.02).
Strongly prognostic in APC treated with ADT +/- AAP is Decipher GC. Although the absolute benefit varied, the AAP impact was constant throughout the AR-A, PAM50, PSC, and GC categories. In order to potentially employ mRNA signatures in the therapy intensification or de-intensification of patients receiving ADT + AAP, they clinically qualified them.
Reference: annalsofoncology.org/article/S0923-7534(22)03342-7/fulltext
