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Multicenter Study
. 2020 Dec 1;6(12):1912-1920.
doi: 10.1001/jamaoncol.2020.4922.

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate

Robert T Dess  1 , Krithika Suresh  2 , Michael J Zelefsky  3 , Stephen J Freedland  4   5 , Brandon A Mahal  6 , Matthew R Cooperberg  7 , Brian J Davis  8 , Eric M Horwitz  9 , Martha K Terris  10 , Christopher L Amling  11 , William J Aronson  12 , Christopher J Kane  13 , William C Jackson  1 , Jason W D Hearn  1 , Curtiland Deville  14 , Theodore L DeWeese  14 , Stephen Greco  14 , Todd R McNutt  14 , Daniel Y Song  14 , Yilun Sun  1   15 , Rohit Mehra  16 , Samuel D Kaffenberger  17 , Todd M Morgan  17 , Paul L Nguyen  18 , Felix Y Feng  7   19   20 , Vidit Sharma  21 , Phuoc T Tran  14 , Bradley J Stish  8 , Thomas M Pisansky  8 , Nicholas G Zaorsky  22 , Fabio Ynoe Moraes  23 , Alejandro Berlin  24   25 , Antonio Finelli  26   27 , Nicola Fossati  28 , Giorgio Gandaglia  28 , Alberto Briganti  28 , Peter R Carroll  7 , R Jeffrey Karnes  21 , Michael W Kattan  29 , Matthew J Schipper  1   15 , Daniel E Spratt  1
Affiliations
Multicenter Study

Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate

Robert T Dess et al. JAMA Oncol. .

Abstract

Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.

Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.

Design, setting, and participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.

Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.

Main outcomes and measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.

Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).

Conclusions and relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Mahal reported receiving grants from Prostate Cancer Foundation, American Society for Radiation Oncology, and the Department of Defense and other from Genzyme Corporation, The Exeter Group, and Prostate Health Education Network outside the submitted work. Dr Cooperberg reported receiving personal fees from Astellas Pharma US, Inc, Bayer AG, MDxHealth, Myriad Genetics, Inc, Dendreon Pharmaceutical LLC, Steba biotech, AstraZeneca, and AbbVie, Inc, outside the submitted work. Dr McNutt reported being the founder of Oncospace, Inc, outside the submitted work and having a patent GPU Convolution Superposition with royalties paid to Sun Nuclear, XStrahl, and a patent Shape based autoplanning with royalties paid to Oncospace, Inc. Dr Song reported receiving grants and consulting support from BioProtect Ltd and grants from Bristol Myers Squibb and Bayer AG outside the submitted work. Dr Kaffenberger reported receiving personal fees from MDxHealth and Clovis Oncology and nonfinancial support from Bristol Myers Squibb outside the submitted work. Dr Morgan reported receiving grants from Myriad Genetics, Inc, and Decipher Biosciences, Inc, outside the submitted work. Dr Nguyen reported receiving personal fees from COTA, Ferring Pharmaceuticals, Astellas Pharma US, Inc, Dendreon Pharmaceutical LLC, Blue Earth Diagnostics, and Boston Scientific Corporation, grants and personal fees from Astellas Pharma US, Inc, Bayer AG, and Janssen Pharmaceuticals, Inc, and personal fees and divested equity from Augmenix, Inc, outside the submitted work. Dr Feng reported receiving personal fees from Janssen Oncology, Sanofi, Bayer AG, Celgene Corporation, Blue Earth Diagnostics, Genentech USA Inc, Myovant, Roivant, and Astellas, grants from Zenith Epigenetics Ltd, and other from PFS Genomics and SerImmune outside the submitted work. Dr Tran reported receiving grants from Astellas Pharma US, Inc, and Bayer Healthcare, grants, personal fees, and travel expenses from RefleXion, and personal fees from Noxopharm outside the submitted work and having a patent for Compounds and Methods of Use in Ablative Radiotherapy, Patient 9114158, licensed to Natsar Pharmaceuticals. Dr Finelli reported receiving personal fees from Astellas Pharma US, Inc, Amgen, Inc, Bayer AG, Janssen Pharmaceuticals, Inc, TerSera Therapeutics LLC, Sanofi, AbbVie, Inc, Knight Therapeutics, Inc, and Verity outside the submitted work. Dr Carroll reported serving on the advisory board for Nutcracker Therapeutics (messenger RNA therapy), Francis Medical (tissue ablation), and Insightec (tissue ablation). Dr Karnes reported receiving personal fees and institutional royalties from Decipher Biosciences outside the submitted work. Dr Kattan reported receiving personal fees from Exosome Diagnostics, Inc, and Stratify Genomics outside the submitted work. Dr Schipper reported receiving personal fees from Innovative Analytics outside the submitted work. Dr Spratt reported receiving personal fees from Janssen Pharmaceuticals, Inc, Blue Earth Diagnostics, and AstraZeneca outside the submitted work.

Figures

Figure 1.
Figure 1.. Clinical Prognostic Stage Group Score System for Prostate Cancer–Specific Mortality (PCSM) Prediction in the Validation Cohort
Score stage group IA (0 points) included 1261 patients from the validation cohort (12.9%; 10-year PCSM estimate, 0.3%); Score stage group IB (1-2 points), 2501 patients (25.6%; 10-year PCSM estimate, 0.8%); Score stage group IC (3-4 points), 1901 patients (19.5%; 10-year PCSM estimate, 2.0%); Score stage group IIA (5-6 points), 1554 patients (15.9%; 10-year PCSM estimate, 3.3%); Score stage group IIB (7-8 points), 1208 patients (12.4%; 10-year PCSM estimate, 4.4%); Score stage group IIC (9-10 points), 719 patients (7.4%; 10-year PCSM estimate, 9.5%); Score stage group IIIA (11-12 points), 354 patients (3.6%; 10-year PCSM estimate, 11.7%); Score stage group IIIB (13-16 points), 248 patients (2.5%; 10-year PCSM estimate, 21.2%); and Score stage group IIIC (≥17 points), 23 patients (0.2%; 10-year PCSM estimate, 40.0%).
Figure 2.
Figure 2.. Reclassification of the Current American Joint Committee on Cancer (AJCC) 8th Edition Staging System Using the Proposed Clinical Prognostic Staging Group Score System in the Validation Cohort
Color coding represents percentage of patients with current AJCC 8th edition stage that are reclassified to each new Score stage. Red is 0%. Orange, yellow, and green represent increasing percentages of reclassification.
Figure 3.
Figure 3.. Model Discrimination (C Index) of Models Over Time for Prediction of Prostate Cancer–Specific Mortality in the Validation Cohort
Higher values of C index indicate better discriminatory performance. Error bars indicate bootstrap 95% CIs. AJCC indicates American Joint Committee on Cancer.
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