Health-related quality of life after a diagnosis of bladder cancer: a longitudinal survey over the first year.

OBJECTIVES: To describe the health-related quality of life (HRQoL) of patients in a prospective 12-month observational cohort study of new bladder cancer diagnoses and compare with national cancer and general population surveys. PATIENTS AND METHODS: A prospective UK study in patients with new bladder cancer diagnoses at 13 NHS Trusts. The HRQoL data were collected at 3, 6, 9 and 12 months. Questionnaires used included: the EuroQoL five Dimensions (EQ-5D), European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ)-30-item core, EORTC QLQ-24-item non-muscle-invasive bladder cancer, and EORTC QLQ-30-item muscle-invasive bladder cancer. Results were compared with the Cancer Quality of Life Survey and Health Survey for England. RESULTS: A total of 349 patients were recruited, 296 (85%) completed the first (baseline) and 233 (67%) the final survey. The patients underwent transurethral resection of bladder tumour (TURBT) ± intravesical therapy (238 patients, 80%), radical cystectomy/radiotherapy (51, 17%) or palliation (seven, 2%). At baseline, patients needing radical treatment reported worse HRQoL including lower social function (74.2 vs 83.8, P = 0.002), increased fatigue (31.5 vs 26.1, P = 0.03) and more future worries (39.2 vs 29.4, P = 0.005) than patients who underwent TURBT. Post-treatment surveys showed no change/improvements for patients who underwent TURBT but deterioration for the radically treated cohort. At final survey, reports were similar to baseline, regardless of treatment. Radically treated patients continued to report poorer HRQoL including issues with body image (23.4 vs 12.5, P = 0.007) and male sexual function (75.8 vs 40.4, P < 0.001) compared to those who underwent TURBT. Radically treated patients reported lower EQ-5D utility scores and more problems with usual activities than the general population. DISCUSSION: Patients undergoing TURBT can be reassured regarding HRQoL following treatment. However, those requiring radical treatment report greater changes in HRQoL with the need for appropriate clinical and supportive care to minimise the impact of treatments.

Effect of Robot-Assisted Radical Cystectomy With Intracorporeal Urinary Diversion vs Open Radical Cystectomy on 90-Day Morbidity and Mortality Among Patients With Bladder Cancer: A Randomized Clinical Trial.

Importance: Robot-assisted radical cystectomy is being performed with increasing frequency, but it is unclear whether total intracorporeal surgery improves recovery compared with open radical cystectomy for bladder cancer. Objectives: To compare recovery and morbidity after robot-assisted radical cystectomy with intracorporeal reconstruction vs open radical cystectomy. Design, Setting, and Participants: Randomized clinical trial of patients with nonmetastatic bladder cancer recruited at 9 sites in the UK, from March 2017-March 2020. Follow-up was conducted at 90 days, 6 months, and 12 months, with final follow-up on September 23, 2021. Interventions: Participants were randomized to receive robot-assisted radical cystectomy with intracorporeal reconstruction (n = 169) or open radical cystectomy (n = 169). Main Outcomes and Measures: The primary outcome was the number of days alive and out of the hospital within 90 days of surgery. There were 20 secondary outcomes, including complications, quality of life, disability, stamina, activity levels, and survival. Analyses were adjusted for the type of diversion and center. Results: Among 338 randomized participants, 317 underwent radical cystectomy (mean age, 69 years; 67 women [21%]; 107 [34%] received neoadjuvant chemotherapy; 282 [89%] underwent ileal conduit reconstruction); the primary outcome was analyzed in 305 (96%). The median number of days alive and out of the hospital within 90 days of surgery was 82 (IQR, 76-84) for patients undergoing robotic surgery vs 80 (IQR, 72-83) for open surgery (adjusted difference, 2.2 days [95% CI, 0.50-3.85]; P = .01). Thromboembolic complications (1.9% vs 8.3%; difference, -6.5% [95% CI, -11.4% to -1.4%]) and wound complications (5.6% vs 16.0%; difference, -11.7% [95% CI, -18.6% to -4.6%]) were less common with robotic surgery than open surgery. Participants undergoing open surgery reported worse quality of life vs robotic surgery at 5 weeks (difference in mean European Quality of Life 5-Dimension, 5-Level instrument scores, -0.07 [95% CI, -0.11 to -0.03]; P = .003) and greater disability at 5 weeks (difference in World Health Organization Disability Assessment Schedule 2.0 scores, 0.48 [95% CI, 0.15-0.73]; P = .003) and at 12 weeks (difference in WHODAS 2.0 scores, 0.38 [95% CI, 0.09-0.68]; P = .01); the differences were not significant after 12 weeks. There were no statistically significant differences in cancer recurrence (29/161 [18%] vs 25/156 [16%] after robotic and open surgery, respectively) and overall mortality (23/161 [14.3%] vs 23/156 [14.7%]), respectively) at median follow-up of 18.4 months (IQR, 12.8-21.1). Conclusions and Relevance: Among patients with nonmetastatic bladder cancer undergoing radical cystectomy, treatment with robot-assisted radical cystectomy with intracorporeal urinary diversion vs open radical cystectomy resulted in a statistically significant increase in days alive and out of the hospital over 90 days. However, the clinical importance of these findings remains uncertain. Trial Registration: ISRCTN Identifier: ISRCTN13680280; ClinicalTrials.gov Identifier: NCT03049410.

Current Treatment and Outcomes Benchmark for Locally Advanced or Metastatic Urothelial Cancer From a Large UK-Based Single Centre.

Objectives: To characterize treatment patterns and survival outcomes for patients with locally advanced or metastatic malignancy of the urothelial tract during a period immediately preceding the widespread use of immune checkpoint inhibitors in the UK. Patients and Methods: We retrospectively examined the electronic case notes of patients attending the Leeds Cancer Center, UK with locally advanced or metastatic urothelial carcinoma, receiving chemotherapy between January 2003 and March 2017. Patient characteristics, treatment patterns, and outcomes were collected. Summary and descriptive statistics were calculated for categorical and continuous variables as appropriate. The Kaplan-Meier method was used to estimate median survival and Cox regression proportional hazards model was used to explore relationships between clinical variables and outcome. Results: Two hundred and sixteen patients made up the study cohort, with a median age of 66 years (range: 35-83) and 72.7% being male. First-line treatment consisted of either a cisplatin- (44%) or carboplatin-based regimen (48%) in the majority of patients. Twenty seven percent of patients received a second-line of treatment (most commonly single-agent paclitaxel) following a first-line platinum containing regimen. Grade 4 neutropenia was observed in 19 and 27% of those treated with a first-line cisplatin- and carboplatin-based regimen, respectively. The median overall survival (mOS) of the study cohort was estimated to be 16.2 months (IQR: 10.6-28.3 months). Receipt by patients of cisplatin-based chemotherapy was associated with a longer mOS and this association persisted when survival analysis was adjusted for age, sex, performance status and presence of distant metastases. Conclusions: This study provides a useful benchmark for outcomes achieved in a real-world setting for patients with locally advanced or metastatic UC treated with chemotherapy in the immediate pre-immunotherapy era.

Radiotherapy in localized bladder cancer: what is the evidence?

PURPOSE OF REVIEW: Bladder-sparing bladder treatments have recently been rejuvenated with the introduction of concomitant chemotherapy usually as part of multimodality therapy including endoscopic resection and radiotherapy. This article reviews recent evidence for the role of radiotherapy in the treatment of localized bladder cancer. RECENT FINDINGS: Several single institution series of multimodality radiochemotherapy have shown consistently fair disease-specific survival and local control in those who show a complete response after endoscopic resection. Developments in radiotherapy fractionation, adaptive planning and chemotherapy delivery are clearly in progress. SUMMARY: Much of the evidence is retrospective and involves treating locally advanced poor-risk patients. It would seem right to attempt to prospectively evaluate these treatments for truly localized (T1/2) bladder cancer.

Fulguration of the lumen does not improve vasectomy sterilization rates.

OBJECTIVES: To assess the effect of adding lumen diathermy fulguration to our standard technique of vas ligation with polyglactin 910 (Vicryl(TM), Ethicon, Sommerville, NJ, USA) excision and fascial interposition, in an attempt to improve our sterilization rates. We previously reported the effect of changing suture material on vasectomy success rates; 3005 post-vasectomy semen analyses (PVSA) revealed a decrease in sterilization rates after surgery on changing from chromic catgut to polyglactin 910. PATIENTS AND METHODS: We retrospectively reviewed PVSA undertaken for vasectomies performed by urological surgeons at the Mid-Yorkshire NHS Trust for 18 months from September 2005 to February 2007. RESULTS: There were 592 vasectomies in all; the age distribution of patients between the groups treated with the standard and new method was similar. Overall, 166 patients (28%) failed to provide two semen samples as instructed, and so were excluded from further analyses. Sterility was achieved in 367 patients (86%); a further 28 (7%) have indeterminate analyses to date, with one of the last two PVSAs showing sperm, with the PVSA of 32 (7%) patients showing persisting sperm. For the eight surgeons reviewed the sterility rates were broadly similar. CONCLUSIONS: The introduction of diathermy fulguration of the lumen has not improved vasectomy sterilization rates, with up to 14% having sperm on PVSA.

Similar treatment outcomes for radical cystectomy and radical radiotherapy in invasive bladder cancer treated at a United Kingdom specialist treatment center.

PURPOSE: To conduct a retrospective analysis within a large university teaching hospital, comparing outcomes between patients receiving either radical surgery or radiotherapy as curative treatment for bladder cancer. PATIENTS AND METHODS: Between March 1996 and December 2000, 169 patients were treated radically for muscle-invasive bladder cancer. Data were collected from patient notes. Statistical analyses were performed using Kaplan-Meier methods and Cox proportional hazards regression analysis to compare radiotherapy and surgical outcome data. RESULTS: There was no difference in overall, cause-specific, and distant recurrence-free survival at 5 years between the two groups, despite the radiotherapy group being older (median age, 75.3 years vs. 68.2 years). There were 31 local bladder recurrences in the radiotherapy group (24 solitary), but there was no significant difference in distant recurrence-free survival. In a more recent (2002-2006) cohort, the median age of radiotherapy patients but not the cystectomy patients was higher than in the 1996-2000 cohort (78.4 years vs. 75.3 years for radiotherapy and 67.9 years vs. 68.2 years for surgery). CONCLUSIONS: Although the patients undergoing radical cystectomy were significantly younger than the radiotherapy patients, treatment modality did not influence survival. Bladder cancer patients are an increasingly elderly group. Radical radiotherapy is a viable treatment option for these patients, with the advantage of organ preservation.

Does failure of single hormone therapy delineate hormone refractoriness for prostate cancer?

OBJECTIVE: The results of two randomized phase III trials have shown benefit with docetaxel-based chemotherapy in advanced prostate cancer patients who had disease progression following primary androgen ablation therapy. In these trials, 50% and 45% of patients, respectively had at least a 50% reduction in prostate-specific antigen (PSA) levels, with median survival times of 17.5 and 18.9 months, respectively. Because the definition of hormone-refractory disease is very loose, it is important that all benefit from hormones has been achieved in these hormone-sensitive tumours. This led us to review our prostate cancer patients treated with secondary hormone manipulations. MATERIAL AND METHODS: Advanced prostate cancer patients treated with two or more modalities of hormone therapy, i.e. anti-androgens, luteinizing hormone-releasing hormone and estrogens, were identified and the treatment response in terms of reduction in PSA levels was assessed. RESULTS: Overall, 65 patients were included in the study. The majority of patients responded to second- (81.9%) or third-line (77.8%) hormone manipulations, irrespective of whether they had localized or advanced prostate disease. Patients who showed any degree of PSA response to second-line hormone manipulation had a median PSA response duration of 6.1 months (range 0.6-27.0 months). Similarly, the median duration of PSA response to third-line hormone therapy was 6.35 months (range 1.9-15.4 months). The duration of PSA control appears to be better among patients with a > 50% PSA response to both second- and third-line hormone manipulation. However, patients with a lower degree of PSA response to the hormone manipulations also demonstrate PSA control of significant duration. CONCLUSIONS: Most patients with a PSA response after primary hormone therapy show a further response to hormones before becoming truly hormone-refractory. There is a concern that the rush to use novel agents will reduce the period of successful palliation in these patients rather than being additive. Patients should show complete hormone refractoriness before newer agents are added to prostate cancer treatment.

Unusual squamous cell carcinoma of the scrotum arising from a well healed, innocuous scar of an infertility procedure: a case report.

A novel case of squamous cell carcinoma of scrotum that developed in a well-healed, uncomplicated scar following an infertility procedure.

Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study.

PURPOSE: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non-muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for molecular diagnosis of disease stage and carcinoma in situ (CIS) and for predicting disease recurrence and progression. EXPERIMENTAL DESIGN: We analyzed tumors from 404 patients diagnosed with bladder cancer in hospitals in Denmark, Sweden, England, Spain, and France using custom microarrays. Molecular classifications were compared with pathologic diagnosis and clinical outcome. RESULTS: Classification of disease stage using a 52-gene classifier was found to be highly significantly correlated with pathologic stage (P < 0.001). Furthermore, the classifier added information regarding disease progression of T(a) or T(1) tumors (P < 0.001). The molecular 88-gene progression classifier was highly significantly correlated with progression-free survival (P < 0.001) and cancer-specific survival (P = 0.001). Multivariate Cox regression analysis showed the progression classifier to be an independently significant variable associated with disease progression after adjustment for age, sex, stage, grade, and treatment (hazard ratio, 2.3; P = 0.007). The diagnosis of CIS using a 68-gene classifier showed a highly significant correlation with histopathologic CIS diagnosis (odds ratio, 5.8; P < 0.001) in multivariate logistic regression analysis. CONCLUSION: This multicenter validation study confirms in an independent series the clinical utility of molecular classifiers to predict the outcome of patients initially diagnosed with non-muscle-invasive bladder cancer. This information may be useful to better guide patient treatment.

Contribution of germline BRCA1 and BRCA2 sequence alterations to breast cancer in Northern India.

BACKGROUND: A large number of distinct mutations in the BRCA1 and BRCA2 genes have been reported worldwide, but little is known regarding the role of these inherited susceptibility genes in breast cancer risk among Indian women. We investigated the distribution and the nature of BRCA1 and BRCA2 germline mutations and polymorphisms in a cohort of 204 Indian breast cancer patients and 140 age-matched controls. METHOD: Cases were selected with regard to early onset disease (< or =40 years) and family history of breast and ovarian cancer. Two hundred four breast cancer cases along with 140 age-matched controls were analyzed for mutations. All coding regions and exon-intron boundaries of the BRCA1 and BRCA2 genes were screened by heteroduplex analysis followed by direct sequencing of detected variants. RESULTS: In total, 18 genetic alterations were identified. Three deleterious frame-shift mutations (185delAG in exon 2; 4184del4 and 3596del4 in exon 11) were identified in BRCA1, along with one missense mutation (K1667R), one 5'UTR alteration (22C>G), three intronic variants (IVS10-12delG, IVS13+2T>C, IVS7+38T>C) and one silent substitution (5154C>T). Similarly three pathogenic protein-truncating mutations (6376insAA in exon 11, 8576insC in exon19, and 9999delA in exon 27) along with one missense mutation (A2951T), four intronic alterations (IVS2+90T>A, IVS7+75A>T, IVS8+56C>T, IVS25+58insG) and one silent substitution (1593A>G) were identified in BRCA2. Four previously reported polymorphisms (K1183R, S1613G, and M1652I in BRCA1, and 7470A>G in BRCA2) were detected in both controls and breast cancer patients. Rare BRCA1/2 sequence alterations were observed in 15 out of 105 (14.2%) early-onset cases without family history and 11.7% (4/34) breast cancer cases with family history. Of these, six were pathogenic protein truncating mutations. In addition, several variants of uncertain clinical significance were identified. Among these are two missense variants, one alteration of a consensus splice donor sequence, and a variant that potentially disrupts translational initiation. CONCLUSION: BRCA1 and BRCA2 mutations appear to account for a lower proportion of breast cancer patients at increased risk of harboring such mutations in Northern India (6/204, 2.9%) than has been reported in other populations. However, given the limited extent of reported family history among these patients, the observed mutation frequency is not dissimilar from that reported in other cohorts of early onset breast cancer patients. Several of the identified mutations are unique and novel to Indian patients.