Biology of BCG response in non-muscle invasive bladder cancer - 2021 IBCN Updates Part III.

Bacillus Calmette-Guerin (BCG) remains the only FDA-approved first-line therapy in patients with high-risk non-muscle invasive bladder cancer. Recurrences, even after adequate BCG therapy, are common and the efficacy of second-line therapies remains modest. Therefore, early identification of patients likely to recur and treatment after recurrence remain critical unmet needs in the clinical care of bladder cancer patients. To address these deficits, a better understanding of the mechanisms of resistance to BCG-therapy is needed. The virtual update of the International Bladder Cancer Network (IBCN) on the biology of response to BCG focused on potential mechanisms and markers of resistance to intravesical BCG therapy. The insights from this meeting will be highlighted and put into context of previously reported mechanisms of resistance to BCG in this review.

Pursuing Quality in the Application of Bladder Cancer Quality of Life Research.

Patient-reported outcomes (PRO), including health-related quality of life (HRQOL) measures, represent important means for evaluating patients' health outcomes and for guiding health care decisions made by patients, practitioners, investigators, and policy makers. In spite of the large number of studies examining HRQOL in patients with bladder cancer, very few review articles investigated this topic. Because these review studies report mixed results, incorporating bladder cancer HRQOL measures into standard urological practice is not a viable option. In this non-systematic review of the literature and commentary we note some general concerns regarding PRO research, but our primary focus is on the HRQOL methodology within the context of two types of bladder cancer: muscle invasive and non-muscle invasive bladder cancer. Considering bladder cancer HRQOL as the interaction of four areas of the assessment process (i.e., what model of HRQOL to choose, what instruments are available to fit the choice, how interpretation of the resulting data fits the model, and how to derive some utility from the chosen model) and the two types of disease (i.e., muscle invasive and non-muscle invasive) may move us toward a better understanding of bladder cancer HRQOL. Establishing a useful model of perceived general health or specific symptoms is the first and most important step in developing the responsive bladder cancer HRQOL measures necessitated by clinical settings.

Outcomes in patients undergoing nephrectomy for renal cancer on chronic anticoagulation therapy.

AIMS: To report our experience on surgical resection of renal tumors for patients with a history of chronic anticoagulation (ACT) or aspirin use. METHODS: We performed a retrospective analysis of 2473 patients who underwent surgery for renal tumors between 2005 and 2012. Prior to surgery, 172 were on chronic ACT and 695 on aspirin. Multivariable linear and logistic regression models were used to compare transfusion and overall complication rates between patients undergoing renal surgery who were on therapy to patients who were on aspirin and to patients with no therapy. RESULTS: Compared to no therapy and aspirin patients those on ACT were older (57.3 (IQR 48.4-66.10) vs 63.9, (IQR 57.3-71.5) vs 68.4, (IQR 60.4-73.5); p < 0.001), with a higher percentage having an ASA score of 3 or 4 (42.4 vs 57.9 vs 82.6%; p < 0.001), respectively. ACT patients had a higher 30-day transfusion rate, 22.7% vs 7.6% vs 6.9%, and 90-day complication rate, 17.4% vs 7.2% vs 7.3%, both p < 0.001. The median length of stay differed statistically between groups (p < 0.001), with a modest longer stay in the anticoagulation group (OR 1.11 SE 0.26; p < 0.001). Transfusion and complication rates for patients on therapy undergoing minimally invasive surgery vs open surgery were not statistically different. CONCLUSIONS: Patients on chronic ACT had higher transfusion and overall complication rates compared to patients on no treatment or on chronic aspirin. These findings did not correlate to clinical differences in length of stay or grade 3-5 complications.

Radical cystectomy and orthotopic urinary reconstruction in patients with bladder cancer after renal transplantation: clinical outcomes and description of technique.

OBJECTIVES: Radical cystectomy (RC) with pelvic lymph node dissection and urinary diversion is the standard treatment for muscle-invasive bladder cancer. In the setting of prior renal transplantation, surgical treatment remains the mainstay but is technically challenging. We report our patient outcomes in this unique population with a description of the technique. METHODS: We identified five patients with a history of renal transplantation who underwent RC and orthotopic urinary diversion. Preoperative clinical and demographic features were compiled and disease-specific and functional outcomes were assessed. Intraoperative technical challenges and maneuvers for avoiding complications are highlighted. RESULTS: Four patients were male and one was female, with a median age of 64 years. Gross hematuria was the most common sign at presentation. Clinical staging was T2, T2 with carcinoma in situ (CIS), high-grade (HG) Ta with CIS, T2 with squamous differentiation, and HG T1, and pathologic tumor stage was pTisN1, pT3N0, pTisN0, pT3N0, and pT0N0, respectively. One patient received a Studer-type diversion and four underwent Hautmann diversion. Median follow-up after cystectomy was 12.9 months. Graft ureteral identification was aided by the use of intravenous dye in all patients. Ipsilateral pelvic lymph node dissection was not possible in any patient. All patients are alive at follow-up, with two experiencing recurrence at 7.2 months and 66.8 months. No patient experienced a significant decrease in estimated creatinine clearance postoperatively. Postoperative daytime control was reported by all patients whereas two noted complete nighttime control. CONCLUSIONS: RC with orthotopic diversion is a technically demanding procedure in patients with a history renal transplantation. Meticulous technique and careful attention to the altered anatomy are required for successful outcomes.

Soy isoflavonoids and cancer prevention. Underlying biochemical and pharmacological issues.

The isoflavonoids in soy, genistein and daidzein, have been proposed to contribute an important part of the anti-cancer effect of soy. Although there have been many interesting studies on the effects of isoflavones on biochemical targets in tissue culture experiments, in most cases the concentrations used by investigators have exceeded 10 microM. However, based on simple pharmacokinetic calculations involving daily intake of isoflavones, absorption from the gut, distribution to peripheral tissues, and excretion, it is unlikely that blood isoflavone concentrations even in high soy consumers could be greater than 1-5 microM. Experiments designed to evaluate these pharmacological principles were carried out in anesthetized rats with indwelling biliary catheters and in human volunteers consuming soy beverages. The data from these experiments indicate that genistein is efficiently absorbed from the gut, taken up by the liver and excreted in the bile as its 7-O-beta-glucuronide. Re-infused genistein 7-O-beta-glucuronide was also well absorbed from the gut, although this occurred in the distal small intestine. In human subjects fed a soy beverage for a period of two weeks, plasma levels of genistein and daidzein, determined by HPLC-mass spectrometry, ranged from 0.55-0.86 microM, mostly as glucuronide and sulfate conjugates. In summary, genistein is well absorbed from the small intestine and undergoes an enterohepatic circulation. Although the plasma genistein levels achievable with soy food feeding are unlikely to be sufficient to inhibit the growth of mature, established breast cancer cells by chemotherapeutic-like mechanisms, these levels are sufficient to regulate the proliferation of epithelial cells in the breast and thereby may cause a chemopreventive effect.