Impact of clinical versus radiographic progression on clinical outcomes in metastatic castration-resistant prostate cancer Journal Article
| Authors: | Rao, A.; Scher, H. I.; De Porre, P.; Yu, M. K.; Londhe, A.; Qi, K.; Morris, M. J.; Ryan, C. |
| Article Title: | Impact of clinical versus radiographic progression on clinical outcomes in metastatic castration-resistant prostate cancer |
| Abstract: | Objectives Unequivocal clinical progression (UCP)-a worsening of clinical status with or without radiographic progression (RAD)-represents a distinct mode of disease progression in metastatic prostate cancer. We evaluated the prevalence, risk factors and the impact of UCP on survival outcomes. Methods A post-hoc analysis of the COU-AA-302, a randomised phase 3 study of abiraterone plus prednisone (AAP) versus prednisone was performed. Baseline characteristics were summarised. Cox proportional-hazards model and Kaplan-Meier method were used for survival and time to event analyses, respectively. Iterative multiple imputation method was used for correlation between clinicoradiographic progression-free survival (crPFS) and overall survival (OS). Results Of 736 patients with disease progression, 280 (38%) had UCP-only and 124 (17%) had UCP plus RAD. Prognostic index model high-risk group was associated with increased likelihood of UCP (p<0.0001). Median OS was 25.7 months in UCP-only and 33.0 months for RAD-only (HR 1.39; 95%CI 1.16 to 1.66; p=0.0003). UCP adversely impacted OS in both treatment groups. Lowest OS was seen in patients with prostate specific antigen (PSA)-non-response plus UCP-only progression (median OS 22.6 months (95%CI 20.7 to 24.4)). Including UCP events lowered estimates of treatment benefit-median crPFS was 13.3 months (95%CI 11.1 to 13.8) versus median rPFS of 16.5 months (95%CI 13.8 to 16.8) in AAP group. Finally, crPFS showed high correlation with OS (r=0.67; 95%CI 0.63 to 0.71). Conclusions UCP is a common and clinically relevant phenomenon in patients with metastatic castration-resistant prostate cancer (mCRPC) treated with AAP or prednisone. UCP is prognostic and associated with inferior OS and post-progression survival. A combination of PSA-non-response and UCP identifies patients with poorest survival. When included in PFS analysis, UCP diminishes estimates of treatment benefit. Continued study of UCP in mCRPC is warranted. © 2020 Author(s) |
| Keywords: | survival; abiraterone; metastatic castration-resistant prostate cancer; no longer clinically benefiting (nlcb); unequivocal clinical progression |
| Journal Title: | ESMO Open |
| Volume: | 5 |
| Issue: | 6 |
| ISSN: | 2059-7029 |
| Publisher: | European Society for Medical Oncology |
| Date Published: | 2020-11-01 |
| Start Page: | e000943 |
| Language: | English |
| DOI: | 10.1136/esmoopen-2020-000943 |
| PUBMED: | 33184097 |
| PROVIDER: | scopus |
| PMCID: | PMC7662417 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 December 2020 -- Source: Scopus |
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