Selma Masic1, Janet E Cowan2, Samuel L Washington2, Hao G Nguyen2, Katsuto Shinohara2, Matthew R Cooperberg3, Peter R Carroll2. 1. Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. Electronic address: selma.masic@ucsf.edu. 2. Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA. 3. Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
Abstract
BACKGROUND: Whether men with Gleason 3+4 prostate cancer are appropriate active surveillance (AS) candidates remains a matter of debate. OBJECTIVE: to evaluate the effects of initial Gleason grade 3+3 or 3+4 on clinical outcomes during AS. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed outcomes for men on AS between 1990 and 2016 with Gleason 3+3 or 3+4 who had two or more biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated associations of diagnostic grade with reclassification (upgrade ≥ 3+4), treatment, metastasis, adverse surgical pathology, and biochemical recurrence (BCR) after deferred radical prostatectomy (RP), with a sensitivity analysis for the amount of pattern 4 disease. RESULTS AND LIMITATIONS: Of 1243 men, 1119 (90%) had Gleason 3+3 and 124 (10%) 3+4 on initial biopsy. The 5-yr unadjusted reclassification-free survival was 49% regardless of grade, while patients with Gleason 3+4 had lower treatment-free survival (49% vs 64%; p<0.01). On multivariate Cox analysis, grade was associated with lower risk of reclassification (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.95) and higher risk of treatment (HR 1.37, 95% CI 1.01-1.85). After RP, patients starting with Gleason 3+4 had lower unadjusted 2-yr BCR-free survival (69% vs 93%; p=0.01) and a higher risk of recurrence (HR 3.67, 95% CI 1.30-10.36). Grade was not associated with metastasis (<1% at 5 yr) or adverse pathology. In sensitivity analyses, a single high-grade core was associated with lower risk of reclassification and multiple high-grade cores were associated with a higher risk of treatment. The number of high-grade cores was not independently associated with BCR. Limitations include selection bias, a limited number of intermediate-risk patients, and length of follow-up. CONCLUSIONS: Gleason 3+4 at diagnosis was associated with risk of reclassification, treatment, and BCR. The number of high-grade cores may help in stratifying men with Gleason 3+4 disease. PATIENT SUMMARY: Some men with Gleason 3+4 prostate cancer may be appropriate surveillance candidates, but longer follow-up and evaluation of more patients are necessary.
BACKGROUND: Whether men with Gleason 3+4 prostate cancer are appropriate active surveillance (AS) candidates remains a matter of debate. OBJECTIVE: to evaluate the effects of initial Gleason grade 3+3 or 3+4 on clinical outcomes during AS. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed outcomes for men on AS between 1990 and 2016 with Gleason 3+3 or 3+4 who had two or more biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We evaluated associations of diagnostic grade with reclassification (upgrade ≥ 3+4), treatment, metastasis, adverse surgical pathology, and biochemical recurrence (BCR) after deferred radical prostatectomy (RP), with a sensitivity analysis for the amount of pattern 4 disease. RESULTS AND LIMITATIONS: Of 1243 men, 1119 (90%) had Gleason 3+3 and 124 (10%) 3+4 on initial biopsy. The 5-yr unadjusted reclassification-free survival was 49% regardless of grade, while patients with Gleason 3+4 had lower treatment-free survival (49% vs 64%; p<0.01). On multivariate Cox analysis, grade was associated with lower risk of reclassification (hazard ratio [HR] 0.66, 95% confidence interval [CI] 0.46-0.95) and higher risk of treatment (HR 1.37, 95% CI 1.01-1.85). After RP, patients starting with Gleason 3+4 had lower unadjusted 2-yr BCR-free survival (69% vs 93%; p=0.01) and a higher risk of recurrence (HR 3.67, 95% CI 1.30-10.36). Grade was not associated with metastasis (<1% at 5 yr) or adverse pathology. In sensitivity analyses, a single high-grade core was associated with lower risk of reclassification and multiple high-grade cores were associated with a higher risk of treatment. The number of high-grade cores was not independently associated with BCR. Limitations include selection bias, a limited number of intermediate-risk patients, and length of follow-up. CONCLUSIONS: Gleason 3+4 at diagnosis was associated with risk of reclassification, treatment, and BCR. The number of high-grade cores may help in stratifying men with Gleason 3+4 disease. PATIENT SUMMARY: Some men with Gleason 3+4 prostate cancer may be appropriate surveillance candidates, but longer follow-up and evaluation of more patients are necessary.
Authors: Adrian J Waisman Malaret; Peter Chang; Kehao Zhu; Yingye Zheng; Lisa F Newcomb; Menghan Liu; Jesse K McKenney; James D Brooks; Peter Carroll; Atreya Dash; Christopher P Filson; Martin E Gleave; Michael Liss; Frances M Martin; Todd M Morgan; Peter S Nelson; Daniel W Lin; Andrew A Wagner Journal: J Urol Date: 2021-12-02 Impact factor: 7.450
Authors: Benedikt Hoeh; Rocco Flammia; Lukas Hohenhorst; Gabriele Sorce; Francesco Chierigo; Zhe Tian; Fred Saad; Michele Gallucci; Alberto Briganti; Carlo Terrone; Shahrokh F Shariat; Markus Graefen; Derya Tilki; Luis A Kluth; Philipp Mandel; Felix K H Chun; Pierre I Karakiewicz Journal: Prostate Int Date: 2022-01-26
Authors: Matthew R Cooperberg; Yingye Zheng; Anna V Faino; Lisa F Newcomb; Kehao Zhu; Janet E Cowan; James D Brooks; Atreya Dash; Martin E Gleave; Frances Martin; Todd M Morgan; Peter S Nelson; Ian M Thompson; Andrew A Wagner; Peter R Carroll; Daniel W Lin Journal: JAMA Oncol Date: 2020-10-08 Impact factor: 31.777
Authors: Neal Shore; Steven A Kaplan; Ronald Tutrone; Richard Levin; James Bailen; Alan Hay; Susan Kalota; Mohamed Bidair; Sheldon Freedman; Kenneth Goldberg; Frederick Snoy; Jonathan I Epstein Journal: World J Urol Date: 2020-02-22 Impact factor: 4.226