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Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics

Prostate Cancer and Prostatic Diseases volume 25, pages 713–719 (2022)Cite this article

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Abstract

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.

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Fig. 1: Clinical outcomes for metastatic castration sensitive prostate cancer stratified by disease volume.
Fig. 2: Patient population similarities between disease volumes.
Fig. 3: Frequency of driver mutations across the spectrum of mCSPC.
Fig. 4: Clinical outcomes stratified by TP53 mutational status.

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Authors and Affiliations

  1. Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Philip Sutera, Daniel Y. Song, Stephen Greco, Curtiland Deville, Theodore DeWeese, Phuoc T. Tran & Matthew P. Deek

  2. Departments of Pathology and human structure and repair, University of Ghent, Ghent, Belgium

    Kim Van Der Eecken

  3. Department of Radiation Oncology, UCLA, Los Angeles, CA, USA

    Amar U. Kishan

  4. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA

    Anis Hamid

  5. Department of Oncology, UCL Cancer Institute, London, UK

    Emily Grist

  6. Division of Molecular Pathology, The Institute of Cancer Research, London, UK

    Gerhardt Attard

  7. Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Tamara Lotan & Adrianna A. Mendes

  8. Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Channing J. Paller, Michael A. Carducci, Ken Pienta, Emmanuel S. Antonarakis, Daniel Y. Song, Theodore DeWeese & Phuoc T. Tran

  9. Department of Urology, Northwestern University, Chicago, IL, USA

    Ashley Ross

  10. Division of Biostatistics and Bioinformatics, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Hao Wang

  11. James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Ken Pienta, Daniel Y. Song, Theodore DeWeese & Phuoc T. Tran

  12. Departments of Radiation Oncology, Medicine and Urology, UCSF, San Francisco, CA, USA

    Felix Y. Feng

  13. Department of Radiation Oncology, Iridium Network, Antwerp, Belgium and Department of human structure and repair, Ghent University, Ghent, Belgium

    Piet Ost

  14. Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, USA

    Matthew P. Deek

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  1. Philip Sutera
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Contributions

Study concept and design: PS, PTT, MPD. Acquisition of data: PS, PTT, MPD. Drafting of manuscript: PS, PTT, MPD. Critical review of manuscript: PS, KVDE, AUK, AH, EG, GA, TL, AAM, CJP, MAC, AR, HW, KP, FYF, ESA, PO, DYS, SG, CD, TD, PTT, MPD.

Corresponding author

Correspondence to Matthew P. Deek.

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Competing interests

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.

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Sutera, P., Van Der Eecken, K., Kishan, A.U. et al. Definitions of disease burden across the spectrum of metastatic castration-sensitive prostate cancer: comparison by disease outcomes and genomics. Prostate Cancer Prostatic Dis 25, 713–719 (2022). https://doi.org/10.1038/s41391-021-00484-4

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