Low testosterone (T) is highly prevalent in the male population and is associated with frailty, decreased muscle mass, lower health-related quality of life, and premature mortality.^1,2 This may predispose patients to poor perioperative outcomes. Prior review of our own institutional data showed that low T was strongly associated with preoperative frailty among veterans undergoing major oncologic surgery.³ However, the prevalence and importance of low T and frailty among men undergoing transurethral resection of bladder tumor (TURBT) remains unknown. Given this, we aimed to determine if low T and frailty are associated with adverse postoperative outcomes in this population.

We performed a retrospective review of men who underwent TURBT and had a preoperative T value <1 year prior to surgery. Low T was defined as total serum T <300 ng/dL in accordance with AUA guideline recommendations.⁴ Two validated metrics of frailty (1) the Hospital Frailty Risk Score (HFRS) which categorizes patients as low-, intermediate-, or high-risk frailty, and (2) the Multimorbidity Frailty Index (mFI-v10) which categorizes patients as fit, mild, moderate, or severe frailty, were used to determine patients’ preoperative frailty.^5,6 We then compared demographics and surgical outcomes including length of stay, preoperative laboratory values, complications, and emergency department visits, readmissions, and mortality rates between cohorts of low T and normal T patients. We also compared oncologic outcomes including tumor stage, grade, presence or absence of carcinoma in situ, multifocality, and tumor size at initial resection.

In total, 308 men were taken to the operating room for endoscopic evaluation and treatment of suspected bladder tumor found on office cystoscopy. Among them, 199 (64.6%) had low T and mean±SD preoperative T in the low T cohort was 164.2±98.3 vs 414.9±165.3 ng/dL in the normal T cohort (P < .001; Table 1). Overall, 156 (50.6%) men were categorized as low-risk frailty, 108 (35.1%) were intermediate-risk frailty, and 44 (14.3%) were high-risk frailty according to the HFRS, with no difference between cohorts (P = .45). A similar pattern was found when comparing frailty between cohorts using the mFI-v10 (P = .64). There was no difference in age, race, emergency department visits, readmissions, or mortality rates between groups. Men with low T had lower mean±SD preoperative hemoglobin compared to men with normal T (12.9±2.0 vs 13.4±1.7, P = .048). Although not statistically significant, there was a trend of decreasing serum T with increasing frailty when stratifying patients using the mFI-v10 (see Figure, P = .09). Subgroup analysis of 83 men who underwent resection of identified bladder tumor showed that low T was not associated with any adverse oncologic outcome (P > .05; Table 2). Lastly, high-risk frailty on the HFRS and severe frailty on the mFI-v10 were associated with postoperative complications on both univariate (OR 3.2, 95% CI [1.3-8.0], P = .01 and OR 4.3, 95% CI [1.8-11.2], P = .002, respectively) and multivariate logistic regression (OR 3.1, 95% CI [1.2-7.8], P = .02 and OR 4.2, 95% CI [1.7-11.3], P = .003, respectively; Table 3).

Table 1. Low Testosterone vs Normal Testosterone and Perioperative Outcomes

Table 2. Low Testosterone vs Normal Testosterone and Oncologic Outcomes for Patients Who Underwent Transurethral Resection of Bladder Tumor

Table 3. Age, Testosterone, Frailty, and Their Association With Postoperative Complications on Both Univariate (Odds Ratio) and Multivariate (Adjusted Odds Ratio) Logistic Regression

Figure. Association of testosterone (ng/dL) and frailty (Multimorbidity Frailty Index [mFI-v10] score).

Our findings show a high prevalence of low T among men undergoing TURBT. Although T was not significantly associated with frailty, high-risk and severe frailty were associated with increased odds of postoperative complications. Importantly, low T had no effect on oncologic outcomes including tumor stage, grade, carcinoma in situ, multifocality, or tumor size. When combined with the proven results and safety of T replacement therapy (TRT) for low T, our findings suggest a possible role for both T and preoperative frailty assessment prior to undergoing TURBT.⁷

These findings may have even further implications for men with high-risk bladder cancer. Approximately 25% of newly diagnosed bladder cancer is muscle-invasive at the time of initial resection, of which over 20% will undergo radical cystectomy.⁸ Radical cystectomy carries significant morbidity and is associated with prolonged length of stay and functional decline. Therefore, identification and possible treatment of low T at the time of initial TURBT could significantly improve patients’ subsequent oncologic treatment course. TRT can increase muscle mass and strength, improve bone density, and contribute to higher health-related quality of life. Therefore, it may offer therapeutic potential as a preoperative intervention in select patients to optimize their functional status prior to surgery. However, further interventional studies are needed to better characterize these potential benefits of TRT in the preoperative setting.

Source of Funding: Urology Care Foundation Research Scholar Award SP0071384.