ICUD-SIU International Consultation on Bladder Cancer 2017: management of non-muscle invasive bladder cancer.

PURPOSE: To provide a summary of the Third International Consultation on Bladder Cancer recommendations for the management of non-muscle invasive bladder cancer (NMIBC). METHODS: A detailed review of the literature was performed focusing on original articles for the management of NMIBC. An international committee assessed and graded the articles based on the Oxford Centre for Evidence-based Medicine system. The entire spectrum of NMIBC was covered such as prognostic factors of recurrence and progression, risk stratification, staging, management of positive urine cytology with negative white light cystoscopy, indications of bladder and prostatic urethral biopsies, management of Ta low grade (LG) and high risk tumors (Ta high grade [HG], T1, carcinoma in situ [CIS]), impact of BCG strain and host on outcomes, management of complications of intravesical therapy, role of alternative therapies, indications for early cystectomy, surveillance strategies, and new treatments. The working group provides several recommendations on the management of NMIBC. RESULTS: Recommendations were summarized with regard to staging; management of primary and recurrent LG Ta and high risk disease, positive urine cytology with negative white light cystoscopy and prostatic urethral involvement; indications for timely cystectomy; and surveillance strategies. CONCLUSION: NMIBC remains a common and challenging malignancy to manage. Accurate staging, grading, and risk stratification are critical determinants of the management and outcomes of these patients. Current tools for risk stratification are limited but informative, and should be used in clinical practice when determining diagnosis, surveillance, and treatment of NMIBC.

Oncologic Outcomes of Definitive Treatments for Low- and Intermediate-Risk Prostate Cancer After a Period of Active Surveillance.

BACKGROUND: To compare oncologic outcomes of different definitive treatment (DT) modalities in a cohort of patients with prostate cancer (PCa) after active surveillance (AS). METHODS: We identified 237 patients with National Comprehensive Cancer Network (NCCN) low- and intermediate-risk prostate cancer diagnosed from 1990 to 2012 who did not undergo immediate DT within 12 months of diagnosis (ie, AS patients as well as watchful waiting and those refusing DT). Charts were examined for clinical/pathologic data and type of DT: surgery (RP), radiation including brachytherapy (XRT), cryotherapy, and androgen deprivation therapy monotherapy (ADT). The impact of DT on oncologic outcomes of biochemical recurrence (BCR), metastasis, disease-specific (DSS), and overall survival (OS) was examined with the Cox proportional hazards model, along with the Kaplan-Meier method and log-rank test. RESULTS: After median time on AS of 63.4 months, 40% of patients underwent DT: 47% XRT, 28% RP, 14% ADT, and 11% cryotherapy. On multivariable analysis, the use of XRT predicted higher BCR (hazard ratio [HR] 6.1, P = .001) and worse overall mortality (HR 2.1, P = .03) compared with other treatments, controlling for age, Charlson Comorbidity Index (CCI), stage, Gleason score, and NCCN risk category. Median follow-up was 71.7 months. On Kaplan-Meier analysis, 10-year OS was superior for RP versus XRT among patients with prostatic specific antigen (PSA) velocity >2.0 ng/mL/y. CONCLUSIONS: Low- and intermediate-risk patients with PCa who progress to DT after AS may be inadequately treated with radiation therapy compared with other DT modalities, especially when pretreatment PSA velocity is > 2 ng/mL/y.

The effect of fibrin clot inhibitors on the immunomodulatory efficacy of Bacillus Calmette-Guérin therapy for non-muscle-invasive bladder cancer.

OBJECTIVE: To determine if there is a difference in clinical outcomes among non-muscle-invasive bladder cancer patients taking fibrin clot-inhibiting (FCI) medications (aspirin, clopidogrel, or warfarin) while receiving Bacillus Calmette-Guérin (BCG) therapy compared with their counterparts not taking anticoagulation. MATERIALS AND METHODS: Our Investigational Review Board-approved database was queried for patients who received an induction course of BCG from 2001 to 2011. The analysis included 224 patients with a minimum of 3 months of follow-up. Recurrence-free survival (RFS), cystectomy-free survival, overall survival, and disease-specific survival were analyzed using the Kaplan-Meier method stratified by FCI status. Logistic regression was used to predict the initial response rate to BCG and progression by FCI status. RESULTS: Of the 224 patients analyzed, 68, 19, and 23 patients were taking aspirin, clopidogrel and warfarin, respectively, at BCG induction. No specific FCI was associated with differences in cystectomy-free survival, overall survival, disease-specific survival, or the likelihood of progression at recurrence. Neither warfarin nor clopidogrel affected RFS. Patients taking aspirin trended toward increased RFS, although this was not statistically significant (P = .058). Multivariate analysis showed aspirin use was associated with an increased initial response to BCG (odds ratio, 2.41; P = .031) CONCLUSION: Contrary to the postulated inhibitory molecular effect of FCI on BCG-binding activity, this study did not substantiate a significant impact on BCG efficacy of the concomitant use of these medications during BCG induction. The observation that aspirin use potentiates an increased initial response to BCG may warrant further analysis.

Two case reports on the use of genistein combined polysaccharide (GCP) against bladder cancer recurrence.

We followed two subjects with resected stage Ta superficial transitional cell carcinoma (TCC) of the bladder who had not received intravesicle bacillus Calmette-Guerin (BCG) and received supplementation with the agent Genistein Combined Polysaccharide (GCP) in an IRB approved study. The observation period was 12 months for both cases. After the yearly oral dosage of GCP, there was no recurrence in either of the subjects as determined by cytoscopy, urine cytology, and fluorescence in-situ hybridization analysis of urine (UrovysionTM FISH Assay). The intravenous pyelogram (IVP), obtained at baseline and after 12 months, was also negative. There were no adverse events over the course of treatment and had full patient compliance and tolerability of the GCP agent in both cases.

Zyflamend in men with high-grade prostatic intraepithelial neoplasia: results of a phase I clinical trial.

Subjects diagnosed with high-grade prostatic intraepithelial neoplasia (HGPIN) at biopsy are at increased risk for developing prostate cancer (CaP). A prospective clinical trial was done to determine the safety and tolerability of a novel herbal amalgam, Zyflamend (New Chapter, Inc., Brattleboro, VT), with various dietary supplements in subjects with HGPIN. Men ages 40 to 75 years with HGPIN were eligible. Subjects were evaluated for 18 months. Every 3 months, standard blood chemistries and prostate-specific antigen (PSA) were monitored. Rebiopsy was done every 6 months. Tissue was evaluated for HGPIN or CaP and stained for cyclooxygenase-2, nuclear factor kappaB (NF-kappaB), interleukin-6, and thromboxane. Twenty-three subjects were evaluable. The median age was 64.1 years (range 46-75 years), and the mean (+/- SD) PSA level was 6.13 +/- 3.56 ng/mL. Side effects, when present, were mild and gastrointestinal in nature. There were no reported serious adverse events or toxicities. No significant changes in blood chemistries, testosterone, or cardiac function were noted. Forty-eight percent of subjects demonstrated a 25 to 50% decrease in PSA after 18 months. Of subjects who had the 18-month biopsy, 60% (9 of 15) had benign tissue, 26.7% (4 of 15) had HGPIN in one core, and 13.3% (2 of 15) had CaP at 18 months. A reduction in serum C-reactive protein was observed (95% confidence interval [CI] 0.7-1.7, p = .045). Immunoreactive staining demonstrated a reduction in NF-kappaB in the 18-month samples (95% CI 0.8-3.0, p = .017). Zyflamend alone and in combination with various dietary supplements is associated with minimal toxicity and no serious adverse events when administered orally for 18 months. Further studies are warranted to evaluate these agents in patients who are at risk for CaP.