Long-Term Outcomes and Genetic Predictors of Response to Metastasis-Directed Therapy Versus Observation in Oligometastatic Prostate Cancer: Analysis of STOMP and ORIOLE Trials

Abstract

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co‐primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The initial STOMP and ORIOLE trial reports suggested that metastasis-directed therapy (MDT) in oligometastatic castration-sensitive prostate cancer (omCSPC) was associated with improved treatment outcomes. Here, we present long-term outcomes of MDT in omCSPC by pooling STOMP and ORIOLE and assess the ability of a high-risk mutational signature to risk stratify outcomes after MDT. The primary end point was progression-free survival (PFS) calculated using the Kaplan-Meier method. High-risk mutations were defined as pathogenic somatic mutations within ATM, BRCA1/ 2, Rb1, or TP53. The median follow-up for the whole group was 52.5 months. Median PFS was prolonged with MDT compared with observation (pooled hazard ratio [HR], 0.44; 95% CI, 0.29 to 0.66; P value < .001), with the largest benefit of MDT in patients with a high-risk mutation (HR high-risk: 0.05; HR no high-risk: 0.42; P value for interaction: .12). Within the MDT cohort, the PFS was 13.4 months in those without a high-risk mutation, compared with 7.5 months in those with a high-risk mutation (HR, 0.53; 95% CI, 0.25 to 1.11; P = .09). Long-term outcomes from the only two randomized trials in omCSPC suggest a sustained clinical benefit to MDT over observation. A high-risk mutational signature may help risk stratify treatment outcomes after MDT.

Management of Patients with Recurrent and Metachronous Oligometastatic Prostate Cancer in the Era of PSMA PET

“…The benefit of MDT was maintained at longer follow-up with five-year data showing a 34% ADT-free survival for the MDT group vs. 8% for the surveillance group, as well as higher castrate-resistant prostate cancer (CRPC)-free survival (76% for MDT vs. 53% for surveillance). A combined analysis of STOMP and ORIOLE also showed that median PFS was prolonged with MDT, compared with observation [ 63 ].…”

How to Improve the Quality of Life of Patients with Prostate Cancer Treated with Hormone Therapy?

“… 113 Finally, the long-term results of these 2 studies confirmed the benefit of MDT in patients with oligorecurrent PC. 114 The results of MDT are therefore promising in order to postpone the start of a systemic therapy and consequently its side effects. However, it must be emphasized that the control arm of the 2 studies was represented by observation which does not represent the standard of care of patients with metastatic PC.…”

Top Ten Lessons Learned from Trials in Oligometastatic Cancers

“…Also in prostate cancer, the STOMP trial demonstrated radiotherapy (RT) or surgery to oligometastases improved androgen-deprivation-therapy-free survival and the ORIOLE trial demonstrated SABR improved PFS in castration-sensitive oligometastatic prostate cancers [ 11 , 12 ]. Pooled analysis from these two latter trials found a PFS benefit with treatment compared to observation (11.9 months vs. 5.9 months) [ 18 ].…”