Association of Age With Risk of Adverse Pathological Findings at Radical Prostatectomy in Men With Gleason Score 6 Prostate Cancer

The preferred treatment for men with low-risk prostate cancer, particularly men older than 65 years, is active surveillance.1 However, advancing age is associated with upgrading and upstaging at radical prostatectomy. Several factors, including increasing prostate-specific antigen (PSA) level, clinical tumor category, percentage of positive biopsy results, and PSA density, have been noted to be associated with clinically significant prostate cancer at radical prostatectomy.2 Until now, to our knowledge, no study has incorporated these factors within predefined age strata to ascertain whether a cohort of patients at high risk can be identified for whom additional evaluation and possible treatment is indicated rather than active surveillance.


Introduction
The preferred treatment for men with low-risk prostate cancer, particularly men older than 65 years, is active surveillance. 1 However, advancing age is associated with upgrading and upstaging at radical prostatectomy. Several factors, including increasing prostate-specific antigen (PSA) level, clinical tumor category, percentage of positive biopsy results, and PSA density, have been noted to be associated with clinically significant prostate cancer at radical prostatectomy. 2 Until now, to our knowledge, no study has incorporated these factors within predefined age strata to ascertain whether a cohort of patients at high risk can be identified for whom additional evaluation and possible treatment is indicated rather than active surveillance.

Methods
This prospective cohort study included men with Gleason score 6 prostate cancer who were treated with radical prostatectomy from February 28, 1992, to February 15, 2016, at the Martini-Klinik Prostate Cancer Center of the University Hospital Hamburg-Eppendorf in Hamburg, Germany. This study was approved, including waivers of consent owing to deidentified data and a no-risk protocol, by the Ethik-Kommission der Ärztekamme institutional review board in Hamburg, Germany. This study was reported following the Consolidated Standards of Reporting Trials (CONSORT) reporting guideline.
We investigated whether men older than 65 years had increased odds of adverse pathological findings at radical prostatectomy, defined as TNM category pT3/T4 or R1 or Gleason score 8, 9, or 10, compared with men 65 years and younger. We dichotomized age at 65 years, a commonly used cutoff, to enable clinical utility of the results. Descriptive statistics were used to compare the proportion of clinical characteristics at presentation among men older than 65 years vs 65 years and younger using a Wilcoxon rank sum test for continuous covariates and the Maental-Haenszal χ 2 test for categorical covariates. 3 Univariable and multivariable logistic regressions were used to calculate unadjusted and adjusted odds ratios (ORs) of adverse pathological findings at radical prostatectomy in men older than 65 years vs men 65 years and younger, adjusting for pre-radical prostatectomy PSA level, clinical tumor category, year of diagnosis, percentage of positive biopsy results, and PSA density. 3  were significantly associated with increased odds of adverse pathological findings at radical prostatectomy ( Table 2), men older than 65 years had higher odds of adverse pathological findings at radical prostatectomy compared with men 65 years and younger (adjusted OR, 1.28, 95% CI, 1.00-1.62; P = .048).

Discussion
This cohort study found that being older than 65 years was associated with adverse pathological findings at radical prostatectomy. Specifically, if being older than 65 years was not associated with increased risk, one would have expected men older than 65 years to have a lower risk of having adverse pathological findings given the more favorable percentage of positive biopsy results and PSA density levels.
Possible explanations for the association of advancing age with risk of adverse pathological features include sampling error and undergrading owing to benign prostatic hyperplasia that occurs normally with advancing age. Another possible explanation is that most men undergo andropause starting at approximately age 40 years continuing to the end of life. 4 Therefore, older men are more likely to have lower testosterone levels at prostate cancer diagnosis compared with younger men, and it is known that prostate cancer in men who are hypogonadal can be more aggressive compared with prostate cancer in men who are eugonadal. 5 This study has some limitations, such as that we chose age 65 years as our cutoff for age, as it is commonly used in prostate cancer studies when