Evolving systemic management of urothelial cancers.

PURPOSE OF REVIEW: Bladder cancer is the 12th most common cancer worldwide. Historically, the systemic management of urothelial carcinoma has been confined to platinum-based chemotherapy. In this review, we discuss the evolving landscape of systemic treatment for urothelial carcinoma. RECENT FINDINGS: Since 2016, when the Food and Drug Administration approved the first immune checkpoint inhibitor (CPI), programmed cell death 1 and programmed cell death ligand 1 inhibitors have been evaluated in the nonmuscle invasive bladder cancer, localized muscle invasive bladder cancer as well as advanced/metastatic bladder cancer settings. Newer approved treatments such as fibroblast growth factor receptor (FGFR) inhibitors and antibody-drug conjugates (ADCs) represent second-line and third-line options. These novel treatments are now being assessed in combination as well as with older traditional platinum-based chemotherapy. SUMMARY: Novel therapies continue to improve bladder cancer outcomes. Personalized approach with well validated biomarkers are important to predict response to therapy.

Factors associated with level of shared decision making in Malaysian primary care consultations.

OBJECTIVE: To measure the level of shared decision-making (SDM) in primary care consultations in Malaysia, a multicultural, middle-income developing country. METHODS: A cross-sectional study was conducted in an urban, public primary care clinic. Convenience sampling was used to recruit participants, and audio-recorded consultations were scored for SDM levels by two independent raters using the OPTION tool. Univariate and multivariate analysis was conducted to determine factors significantly associated with SDM levels. RESULTS: 199 patients and 31 doctors participated. Mean consultation time was 14.3 min (+ SD 5.75). Patients' age ranged from 18 to 87 years (median age of 57.5 years). 52.8 % of patients were female, with three main ethnicities (Malay, Chinese, Indian). The mean OPTION score was found to be 7.8 (+ SD 3.31) out of 48. After a multivariate analysis, only patient ethnicity (ß= -0.142, p < 0.05) and increased consultation time (ß = 0.407, p < 0.01) were associated with higher OPTION scores. CONCLUSIONS: Patients in Malaysia experience extremely poor levels of SDM in general practice. Higher scores were associated with increased consultation time and patient ethnicity. PRACTICE IMPLICATIONS: Malaysian general practitioners should aim to develop and practice cultural competency skills to avoid biased SDM practice towards certain ethnicities.

Novel urinary biomarkers for the detection of bladder cancer: A systematic review.

BACKGROUND: Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date. METHODS: A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918). RESULTS: Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2-94%, specificity of 46-100%, positive predictive value (PPV) of 47-100% and negative predictive value (NPV) of 21-94%. Multi-target biomarkers achieved a sensitivity of 24-100%, specificity of 48-100%, PPV of 42-95% and NPV of 32-100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias. CONCLUSION: This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice.

Intracorporeal robot-assisted radical cystectomy, together with an enhanced recovery programme, improves postoperative outcomes by aggregating marginal gains.

OBJECTIVE: To assess the cumulative effect of an enhanced recovery after surgery (ERAS) pathway and minimally invasive robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) in comparison with open radical cystectomy (ORC) on length of hospital stay (LOS) and peri-operative outcomes. MATERIALS AND METHODS: Between February 2009 and October 2017, 304 radical cystectomy cases were performed at a single institution (ORC, n = 54; robot-assisted radical cystectomy [RARC], n = 250). Data were prospectively collected. We identified 45 consecutive ORC cases performed without ERAS before the commencement of the RARC programme (Cohort A), 50 consecutive iRARC cases performed without ERAS (Cohort B) and 40 iRARC cases with ERAS (Cohort C). The primary outcome measure was LOS, while secondary outcome measures included peri-operative 90-day complications and readmission rate. Complications were accessed using the Clavien-Dindo system. RESULTS: Patients in all cohorts were evenly matched with regard to age, sex, body mass index, neoadjuvant treatment, tumour stage, lymph node yield, previous pelvic radiotherapy and surgery, peri-operative anaemia, as well as physiological state. Patients who underwent iRARC with ERAS had a significantly higher American Society of Anesthesiologists score (III-IV) and were more likely to receive neobladder reconstruction. The median (interquartile range) LOS was shorter in the iRARC with ERAS group (7 [6-10]) days than in the iRARC without ERAS group (11 [8-15]) days and the ORC group (17 [14-21] days). In a propensity score-matched cohort of patients who underwent iRARC, patients who followed the ERAS pathway had significantly lower 90-day readmission rates. Additionally, implementing ERAS in an iRARC cohort resulted in a significantly lower 90-day all (P < 0.001) and gastrointestinal-related complications (P = 0.001). The ERAS pathway and younger patients were independently associated with an LOS of ≤10 days on multinomial logistic regression. CONCLUSION: A comprehensive ERAS programme can significantly reduce LOS in patients undergoing iRARC without increasing 90-day readmission rates. An ERAS programme can augment the benefits of iRARC in improving peri-operative outcomes. In studies comparing ORC and RARC, the presence or absence of an ERAS programme will be a confounding factor and only level 1 evidence can be interpreted reliably.

In-depth Critical Analysis of Complications Following Robot-assisted Radical Cystectomy with Intracorporeal Urinary Diversion.

BACKGROUND: Robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) is an attractive option to open cystectomy, but the benefit in terms of improved outcomes is not established. OBJECTIVE: To evaluate the early postoperative morbidity and mortality of patients undergoing iRARC and conduct a critical analysis of complications using standardised reporting criteria as stratified according to urinary diversion. DESIGN, SETTING, AND PARTICIPANTS: A total of 134 patients underwent iRARC for bladder cancer at a single centre between June 2011 and July 2015. INTERVENTION: Radical cystectomy with iRARC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patient demographics, pathologic data, and 90-d perioperative mortality and complications were recorded. Complications were reported according to the Clavien-Dindo (CD) classification and stratified according to urinary diversion type and either surgical or medical complications. The chi-square test and t test were used for categorical and continuous variables respectively. Multivariable logistic regression was performed on variables with significance in univariate analysis. RESULTS AND LIMITATIONS: The 90-d all complication rate following ileal conduit and continent diversion was 68% and 82.4%, and major complications were 21.0% and 20.6% respectively. The 90-d mortality was 3% and 2.9% for ileal conduit and continent diversion patients, respectively. On multivariate analysis, the blood transfusion requirement was independently associated with major complications (p=0.002) and all 30-d (p=0.002) and 90-d (p=0.012) major complications. Male patients were associated with 90-d major complications (p=0.015). Critical analysis identified that surgical complications were responsible for 39.4% of all 90-d major complications. The incidence of surgical complications did not decline with increasing number of iRARC cases performed (p=0.742, r=0.31). Limitations of this study include its retrospective nature, limited sample size, and limited multivariate analysis due to the low number of major complications events. CONCLUSIONS: Although complications following iRARC are common, most are low grade. A critical analysis identified surgical complications as a cause of major complications. Addressing this issue could have a significant impact on lowering the morbidity associated with iRARC. PATIENT SUMMARY: We looked at the surgical outcomes in bladder cancer patients treated with minimally invasive robotic surgery. We found that surgical complications account for most major complications and previous surgical experience may be a confounding factor when interpreting results from a different centre even in a randomised trial setting.

Blood Transfusion Requirement and Not Preoperative Anemia Are Associated with Perioperative Complications Following Intracorporeal Robot-Assisted Radical Cystectomy.

OBJECTIVES: To assess the prevalence of preoperative anemia and the impact of preoperative anemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS AND METHODS: IRARC was performed on 166 patients between June 2011 and March 2016. Prospective data were collected for patient demographics, clinical and pathologic characteristics, perioperative variables, transfusion requirements, and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan Kettering Cancer Center Clavien-Dindo system. RESULTS: Preoperative anemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p < 0.001). Patients with preoperative anemia were significantly more likely to have an Ileal conduit (p = 0.033), higher cystectomy stage (≥pT3) (p = 0.028), and a lower lymph node yield (p = 0.031). Preoperative anemia was not associated with increased perioperative morbidity but was associated with the requirement for blood transfusion (p = 0.001). Blood transfusion required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9%, respectively. The 30-day all complication rate and 30-day major complication rate were 55.4% and 15.7%, respectively, while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3%, respectively. Intraoperative blood transfusion was not associated with increased complications, but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30-day complications (p = 0.003), all 90-day complications (p = 0.009), and 90-day major complications (p = 0.004). CONCLUSION: The presence of preoperative anemia in patients undergoing iRARC is not associated with increased surgical risk, although preoperative anemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion are independently associated with perioperative morbidity and are an important factor for the optimization of postoperative outcomes.

Well-differentiated Papillary Mesothelioma of the Tunica Vaginalis.

A 39-year-old man presented with painless scrotal swelling for 2 months. He denied any asbestos exposure but worked with wall and ceiling plaster. Physical exam revealed a large right scrotum which transilluminated. Scrotal ultrasonography revealed a large right hydrocele and a polypoidal mass along the anterior wall of the scrotum. Magnetic resonance imaging of the abdomen and computed tomography of the chest showed no metastases. He underwent a right inguinal scrotal exploration and wide excision of tunica vaginalis and a partial epididymectomy. Pathology revealed well-differentiated papillary mesothelioma of the tunica vaginalis. The patient had an uneventful recovery.