Heterogeneity of Radiological Progression Patterns and Association with Outcomes in Patients with Metastatic Prostate Cancer

Abstract

BackgroundWith an increasing number of clinical trials using radiographic progression-free survival (rPFS) instead of overall survival as the primary study endpoint, the heterogeneity of different radiological progression patterns in rPFS and postprogression survival (PPS) remains unclear. ObjectiveHerein, we investigate the proportion of various radiological progression patterns in patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC), and further explore the differences in rPFS and PPS between patients exhibiting single- or multicategory progression patterns. Design, setting, and participantsThis post hoc, retrospective secondary analysis was based on individual patient data from LATITUDE (phase 3 randomized mHSPC study) and COU-AA-302 (phase 3 randomized mCRPC study). Patients with complete imaging follow-up data and radiological progression were included in the analysis. Outcome measurements and statistical analysisThe rPFS and PPS in LATITUDE and COU-AA-302 were evaluated. The proportion of patients exhibiting each progression pattern was calculated, and a survival analysis was conducted using the Kaplan-Meier method. Results and limitationsOf the 489 mHSPC patients studied, 366 experienced single-category progression, while the remaining 123 patients (25.2%) exhibited simultaneous occurrence of different progressive events (multicategory radiological progression). Of the 534 mCRPC patients studied, 390 experienced single-category progression, while the remaining 144 patients (27.0%) experienced multicategory progressive events. Among mCRPC patients, the rPFS of bone progression was the shortest. In contrast, among mHSPC patients, the rPFS of target lesion enlargement is the shortest, followed by bone progression. Notably, patients experiencing a single-category progression pattern displayed comparable rPFS to but significantly longer PPS than those experiencing multicategory progression patterns (PPS mHSPC cohort: 21.5 vs 6.9 mo, p < 0.0001; mCRPC cohort: 23.6 vs 15.7 mo, p < 0.0001). The study is limited by its hypothesis-generating nature. Therefore, the observed phenomena in our research necessitate validation through future prospective studies. ConclusionsPatients who experience multicategory radiological progression represent a significant proportion, accounting for approximately 25% of all men with mHSPC or mCRPC. Patients with multicategory radiological progression patterns had similar rPFS to but significantly shorter PPS than those experiencing single-category progression patterns. In future clinical trials and clinical practice, radiological progression patterns should be recognized as a crucial determinant of prognosis, while also serving as the stratification or inclusion criteria for second-line treatment clinical trials. Patient summaryIn this study, we observed that among men with metastatic prostate cancer, those who experienced two or more radiological events during a single visit had a worse prognosis than those who experienced isolated radiological events.