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Abstract

IMPORTANCE:
The optimal treatment for Gleason score 9-10 prostate cancer is unknown.

OBJECTIVE:
To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment.

DESIGN, SETTING, AND PARTICIPANTS:
Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013.

EXPOSURES:
Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy.

MAIN OUTCOMES AND MEASURES:
The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes.

RESULTS:
Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostatecancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]).

CONCLUSIONS AND RELEVANCE:
Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Author information

Kishan AU1, Cook RR2, Ciezki JP3, Ross AE4, Pomerantz MM5, Nguyen PL6, Shaikh T7, Tran PT8, Sandler KA1, Stock RG9, Merrick GS10, Demanes DJ1, Spratt DE11, Abu-Isa EI11, Wedde TB12, Lilleby W12, Krauss DJ13, Shaw GK5, Alam R4, Reddy CA3, Stephenson AJ14, Klein EA14, Song DY8, Tosoian JJ4, Hegde JV1, Yoo SM1, Fiano R10, D'Amico AV6, Nickols NG1,15, Aronson WJ16, Sadeghi A15, Greco S8, Deville C8, McNutt T8, DeWeese TL8, Reiter RE16, Said JW17, Steinberg ML1, Horwitz EM7, Kupelian PA1,18, King CR1.

1 Department of Radiation Oncology, University of California, Los Angeles.
2 Department of Epidemiology, Fielding School of Public Health, University of California, Los Angeles.
3 Department of Radiation Oncology, Cleveland Clinic, Cleveland, Ohio.
4 Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland.
5 Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
6 Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts.
7 Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, Pennsylvania.
8 Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland.
9 Department of Radiation Oncology, The Icahn School of Medicine at Mount Sinai, New York, New York.
10 Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, West Virginia.
11 Department of Radiation Oncology, University of Michigan, Ann Arbor.
12 Department of Oncology, Oslo University Hospital, the Norwegian Radium Hospital, Oslo, Norway.
13 Oakland University William Beaumont School of Medicine, Royal Oak, Michigan.
14 Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio.
15 Department of Radiation Oncology, Veteran Affairs Greater Los Angeles Healthcare System, Los Angeles, California.
16 Department of Urology, University of California, Los Angeles.
17 Department of Pathology, University of California, Los Angeles.
18 Varian Medical Systems, Palo Alto, California.