Association between Smoking Exposure, Neoadjuvant Chemotherapy Response and Survival Outcomes following Radical Cystectomy: Systematic Review and Meta-Analysis.

PURPOSE: Studies exploring the association of cigarette smoking and long-term survival outcomes following radical cystectomy have yielded mixed results. We performed a systematic review and meta-analysis to investigate the impact of tobacco smoking exposure, duration, intensity and cessation on response to neoadjuvant chemotherapy and long-term survival outcomes in patients undergoing radical cystectomy for bladder cancer. MATERIALS AND METHODS: We systematically searched PubMed®, MEDLINE®, Embase® and Cochrane® Library databases for original articles published before April 2019. Primary end points were neoadjuvant chemotherapy response, overall and cancer specific mortality, and recurrence-free survival after radical cystectomy. Observational studies reporting Cox proportional hazards regression or logistic regression analysis were independently screened. Available multivariable hazard ratios and corresponding 95% CIs were included in the quantitative analysis. Sensitivity analyses were performed as appropriate. A risk of bias assessment was completed for nonrandomized studies. RESULTS: Our electronic search identified a total of 649 articles. After a detailed review we selected 17 studies that addressed the impact of smoking status on survival outcomes in 13,777 patients after radical cystectomy for bladder cancer. Pooled meta-analysis revealed that active smokers have an increased risk of overall mortality (HR 1.21, 95% CI 1.08-1.36; p=0.001, I2=0%), cancer specific mortality (HR 1.24, 95% CI 1.13-1.36; p <0.00001, I2=0%) and bladder cancer recurrence (HR 1.24, 95% CI 1.12-1.38; p <0.0001, I2=3%). Sensitivity analyses evaluating only patients who underwent neoadjuvant chemotherapy followed by radical cystectomy showed an advantage of non/never smokers in terms of neoadjuvant chemotherapy complete response rate (HR 0.47, 95% CI 0.29-0.75; p=0.001, I2=0%). CONCLUSIONS: Smoking status is associated with lower neoadjuvant chemotherapy response rates and higher overall and cancer specific mortality as well as bladder cancer recurrence after radical cystectomy. Appropriate preoperative counseling, together with tightened followup, may have a pivotal role in improving the smoking-related long-term survival outcomes in patients with bladder cancer.

Effect of renal transplantation on sperm quality and sex hormone levels.

OBJECTIVE: To assess the effect of successful renal transplantation on semen variables, sexual function and sex hormone profiles in a clinical trial. PATIENTS AND METHODS: Thirty patients on haemodialysis underwent renal transplantation; before and after surgery, their sperm density, motility and morphology were analysed, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and testosterone levels measured and compared, and sexual function assessed using an abbreviated version of the International Index of Erectile Function (IIEF), with a successful outcome defined as a level of satisfaction of 4 or 5 on a 5-point scale. The paired t-test was used to assess the statistically significance of differences in all analyses. RESULTS: Sperm motility improved significantly (P < 0.001) but there were no significant changes in morphology or density (P = 0.33 and 0.068, respectively). Testosterone levels increased and FSH, LH and prolactin decreased significantly (P < 0.05) after renal transplantation. The IIEF showed that of the 30 patients, 14 were impotent before surgery and only six remained so afterward (P < 0.05). CONCLUSION: Although sperm morphology and density did not improve after renal transplantation, there were highly significant changes in sperm motility. Hormonal levels in patients on haemodialysis improved after transplantation and returned to nearly normal; sexual function was also significantly better. Further studies are needed to confirm these results.