Cyclooxygenase-2 (COX-2) inhibition for prostate cancer chemoprevention: double-blind randomised study of pre-prostatectomy celecoxib or placebo.

OBJECTIVE: To evaluate the biological effects of selective cyclooxygenase-2 inhibition on prostate tissue in patients undergoing radical prostatectomy (RP). PATIENTS AND METHODS: Patients with localised prostate cancer were randomised to receive either celecoxib 400 mg twice daily or placebo for 4 weeks before RP. Specimens were analysed for levels of apoptosis, prostaglandins, and androgen receptor (AR). Effects on serum prostate-specific antigen (PSA) and postoperative opioid use were also measured. RESULTS: In all, 28 of 44 anticipated patients enrolled and completed treatment. One patient in the celecoxib arm had a myocardial infarction postoperatively. For this reason, and safety concerns in other studies, enrolment was halted. The apoptosis index (AI) in tumour cells was 0.29% [95% confidence interval (CI) 0.11-0.47%] vs 0.39% (95% CI 0.00-0.84%) in the celecoxib and placebo arms, respectively (P = 0.68). The AI in benign cells was 0.18% (95% CI 0.03-0.32%) vs 0.13% (95% CI 0.00-0.28%) in the celecoxib and placebo arms, respectively (P = 0.67). Prostaglandin E2 and AR levels were similar in cancerous and benign tissues when comparing the two arms. The median baseline PSA level was 6.0 and 6.2 ng/mL for the celecoxib and placebo groups, respectively, and did not significantly change after celecoxib treatment. There was no difference in postoperative opiate usage between arms. CONCLUSION: Celecoxib had no effect on apoptosis, prostaglandins or AR levels in cancerous or benign prostate tissues. These findings coupled with drug safety concerns should serve to limit interest in these selective drugs as chemopreventive agents.

A phase II study of sulforaphane-rich broccoli sprout extracts in men with recurrent prostate cancer.

INTRODUCTION: Diets high in cruciferous vegetables are associated with lower risk of incidence of prostate cancer, including aggressive forms of this disease. Human intervention studies with cruciferous vegetable-rich diets also demonstrate modulation of gene expression in important pathways in prostate cells. PURPOSE: Sulforaphane is a constituent of these foods postulated to harbor the anti-neoplastic activity based on multiple tumor models. Our own work demonstrates that sulforaphane inhibits AR signaling in prostate cancer cells. Here, we report results from the first clinical trial of sulforaphane-rich extracts in men with prostate cancer. METHODS: We treated 20 patients who had recurrent prostate cancer with 200 µmoles/day of sulforaphane-rich extracts for a maximum period of 20 weeks and determined the proportion of patients with ≥50% PSA declines, the primary endpoint. Only one subject experienced a ≥50% PSA decline. Thus, the primary endpoint was not achieved. Seven patients experienced smaller PSA declines (<50%). There was also a significant lengthening of the on-treatment PSA doubling time (PSADT) compared with the pre-treatment PSADT [6.1 months pre-treatment vs. 9.6 months on-treatment (p = 0.044)]. Finally, treatment with sulforaphane-rich extracts was safe with no Grade 3 adverse events. CONCLUSIONS: Treatment with 200 µmoles/day of sulforaphane-rich extracts did not lead to ≥50% PSA declines in the majority of patients. However, because of the safety of treatment and the effects on PSADT modulation, further studies, including those with higher doses, may be warranted to clarify the role of sulforaphane as a prevention agent or treatment agent.

The end of "Cutting for Stone"? Using the lithoclast trilogy for cystolitholapaxy on a 4 cm bladder stone per urethra.

We present a case of cystolitholapaxy using the LithoClast Trilogy lithotripter device per urethra via a rigid 26F nephroscope in a 36-year-old female with chondrodysplasia, paraplegia, contractures, and history of bladder augment managed with clean intermittent catheterization. The stone was 4cm in diameter with an average of 1300 Hounsfield Units, and composed of 45% calcium phosphate, 40% struvite, and 15% ammonium urate. Advantages include faster fragmentation time versus holmium laser, improved safety with suction extraction and improved vision, ability to treat larger stones endoscopically, and control of all variables by one surgeon with only a single foot pedal.

Open versus robot-assisted radical cystectomy: 30-day perioperative comparison and predictors for cost-to-patient, complication, and readmission.

The objectives of this study are to evaluate if robotic cystectomy demonstrates reduced complications, readmissions, and cost-to-patient compared to open approach 30-day post-operatively, and to identify predictors of complication, readmission, and cost-to-patient. This retrospective cohort study analyzed 249 patients who underwent open (n = 149) or robotic (n = 100) cystectomy from 2009 to 2015 at our institution. Outcomes included 30-day post-operative complication, readmission, and cost-to-patient charges. We used modified Clavien-Dindo/MSKCC classifications. Multivariable logistic and linear regression models were used to evaluate associations to outcomes and to build predictive models. Patient, clinical, and surgical characteristics differed by open and robotic groups, respectively, only for estimated blood loss (median: 600 versus 150 cc, p < 0.01), operative time (mean: 6.19 versus 6.85 h, p < 0.01), and length of stay (median: 7 versus 5 days, p < 0.01). Complication: frequency of patients with at least one 30-day complication was 85% compared to 66% (p < 0.01). Minor gastrointestinal and bleeding complications were increased in the open group (50% versus 41%, p = 0.01; 52% versus 11%, p < 0.01, respectively). Fifty percent of patients required blood transfusion in open compared to 11% (p < 0.01). Patients in the open group experienced more major complications (19% versus 10%, p = 0.04). Robotic approach was a predictor for fewer complications (OR 0.44, 95% CI 0.20-0.99, p = 0.049). Readmission: no significant difference in number of patients readmitted was found. Cost-to-patient: Robotic approach predicted an 18% reduction in total cost-to-patient compared to open approach (p < 0.01). Robotic cystectomy demonstrated reduced total cost-to-patient when taking into account all 30-day post-operative services with fewer complications compared to open cystectomy.

Prolonged response to early docetaxel in a patient with biochemical relapse after primary therapy for prostate cancer and incomplete response to androgen suppression therapy.

Sensitivity to androgen suppression therapy (AST) is a key determinant of survival in patients with non-localized prostate cancer. While an incomplete response to AST is associated with poor survival, additional therapy is typically withheld until obvious cancer progression. It is not known if the application of additional therapy earlier can have a favorable impact on long-term outcomes. We present the case of a patient with biochemically relapsed prostate cancer treated with early docetaxel after initial incomplete response to AST who now has a prolonged response to therapy.