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. 2020 May 15;126(10):2132-2138.
doi: 10.1002/cncr.32778. Epub 2020 Feb 19.

Validation of a subclassification for high-risk prostate cancer in a prospective cohort

Santino S Butler  1 , Edward C Dee  1 , Nayan Lamba  1 , Sybil T Sha  1   2 , Brandon A Mahal  1   3 , Amanda Whitbeck  1 , Rishi Makkar  1 , Janet Wangoe  1 , Kent W Mouw  1 , Paul L Nguyen  1 , Vinayak Muralidhar  1
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Free article

Validation of a subclassification for high-risk prostate cancer in a prospective cohort

Santino S Butler et al. Cancer. .
Free article

Abstract

Background: A subgroup of men with favorable high-risk prostate cancer (T1c with either a Gleason score of 4 + 4 = 8 and a prostate-specific antigen [PSA] level <10 ng/mL or a Gleason score of 6 and a PSA level >20 ng/mL) has been associated with improved outcomes in comparison with other standard high-risk patients. This study was designed to validate the prognostic utility of a subclassification for high-risk disease with a prospectively collected data set.

Methods: This study identified 3033 men from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial who had been diagnosed from 1993 to 2001 with clinically localized prostate cancer-either intermediate-risk disease (clinical stage T2b-c, a Gleason score of 7, or a PSA level of 10 to 20 ng/mL) or high-risk disease (clinical stage T3-T4, a Gleason score of 8-10, or a PSA level >20 ng/mL)-that was managed with radical prostatectomy or radiation therapy. Multivariable logistic regression was used to calculate adjusted odds ratios (aORs) for pathological T3 to T4 or N1 (pT3-T4/pN1) disease. Fine and Gray competing risks regression was used to determine adjusted hazard ratios (aHRs) of prostate cancer-specific mortality (PCSM).

Results: The median follow-up was 5.7 years. Patients with favorable high-risk disease had lower 8-year PCSM in comparison with patients with standard high-risk disease (2.2% vs 10.8%; aHR, 0.26; 95% confidence interval [CI], 0.09-0.73; P = .01) but similar PCSM in comparison with patients with intermediate-risk disease (2.2% vs 2.2%; aHR, 0.90; 95% CI, 0.32-2.54; P = .84). Among those who underwent surgery, those with favorable high-risk disease had lower odds of pT3-T4/pN1 disease than those with standard high-risk disease (46.2% vs 63.3%; aOR, 0.50; 95% CI, 0.27-0.94; P = .03).

Conclusions: This study validates the prognostic utility of a subclassification for high-risk disease in a prospectively collected patient cohort. Patients with favorable high-risk disease have PCSM similar to that of patients with intermediate-risk disease and significantly better than that of patients with standard high-risk disease. Future trials are needed to assess possible de-intensification of therapy for favorable high-risk disease.

Keywords: high-risk prostate cancer; prognosis; proportional hazards models; prostatic neoplasms.

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References

    1. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Prostate Cancer. Version 2.2019, April 17, 2019. Accessed May 1, 2019. https://www.nccn.org/professionals/physician_gls/pdf/prostate.pdf
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    1. Muralidhar V, Chen MH, Reznor G, et al. Definition and validation of “favorable high-risk prostate cancer”: implications for personalizing treatment of radiation-managed patients. Int J Radiat Oncol Biol Phys. 2015;93:828-835.
    1. Muralidhar V, Xiang M, Orio PF III, et al. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer. J Contemp Brachytherapy. 2016;8:1-6.
    1. Muralidhar V, Zhang J, Wang Q, et al. Genomic validation of three-tiered clinical sub-classification of high-risk prostate cancer. Int J Radiat Oncol Biol Phys. 2019;105:621-627.

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