BACKGROUND: Several definitions have attempted to stratify metastatic castrate-sensitive prostate cancer (mCSPC) into low and high-volume states. However, at this time, comparison of these definitions is limited. Here we aim to compare definitions of metastatic volume in mCSPC with respect to clinical outcomes and mutational profiles.
METHODS: We performed a retrospective review of patients with biochemically recurrent or mCSPC whose tumors underwent somatic targeted sequencing. 294 patients were included with median follow-up of 58.3 months. Patients were classified into low and high-volume disease per CHAARTED, STAMPEDE, and two numeric (≤3 and ≤5) definitions. Endpoints including radiographic progression-free survival (rPFS), time to development of castration resistance (tdCRPC), and overall survival (OS) were evaluated with Kaplan-Meier survival curves and log-rank test. The incidence of driver mutations between definitions were compared.
RESULTS: Median OS and tdCRPC were shorter for high-volume than low-volume disease for all four definitions. In the majority of patients (84.7%) metastatic volume classification did not change across all four definitions. High volume disease was significantly associated with worse OS for all four definitions (CHAARTED: HR 2.89; p < 0.01, STAMPEDE: HR 3.82; p < 0.01, numeric ≤3: HR 4.67; p < 0.01, numeric ≤5: HR 3.76; p < 0.01) however, were similar for high (p = 0.95) and low volume (p = 0.79) disease across all four definitions. Those with discordant classification tended to have more aggressive clinical behavior and mutational profiles. Patients with low-volume disease and TP53 mutation experienced a more aggressive course with rPFS more closely mirroring high-volume disease.
CONCLUSIONS: The spectrum of mCSPC was confirmed across four different metastatic definitions for clinical endpoints and genetics. All definitions were generally similar in classification of patients, outcomes, and genetic makeup. Given these findings, the simplicity of numerical definitions might be preferred, especially when integrating metastasis directed therapy. Incorporation of tumor genetics may allow further refinement of current metastatic definitions.
Bibliographical noteFunding Information:
Consultant for Pfizer, Exelexis. ESA: Patent holder/licenser for Qiagen; Consultant for Amgen, Astellas, AstraZeneca, Bayer, Clovis, Dendreon, Eli Lilly and Co. ESSA, GlaxoSmithKline, Jannsen, Medivation, Merck, and Sanofi; Research grant recipient from AstraZeneca, Bristol Myers-Squibb, Celgene, Clovis, Dendreon, Genentech, Janssen, Johnson & Johnson, Merck, Novartis, Sanofi, Tokai. PO: Consultant for Bayer, Janssen, Curium; Research grant recipient from Varian, Bayer. AG: Relationship with Janssen and Astellas; Royalties from ICR. AR: Speaker’s Bureau for Blue Earth and Janssen; Stock Options from Decipher Biosciences; Consultant to Astellas. PT: Research funding from Astellas Pharm, Bayer Healthcare and RefleXion Medial Inc; Consultant for RefleXion, Grants from RefleXion; Personal fees from Noxopharm, Janssen-Taris Biomedical, Myovant and AstraZeneca; Holds a patent 9114158-Compounds and Methods of Use in Ablative Radiotherapy licensed to Natsar Pharm.
© 2021, The Author(s), under exclusive licence to Springer Nature Limited.
PubMed: MeSH publication types
- Journal Article
- Research Support, Non-U.S. Gov't