The impact of patient sex on characteristic-adjusted bladder cancer prognosis.

CONTEXT: Bladder cancer is one of the most common malignancies worldwide. Some studies noted sex differences in the prognosis of bladder cancer, but results are inconsistent. SUBJECTS AND METHODS: In this study, we assessed whether women with bladder cancer exhibit a worse prognosis, after adjustment for disease stage, age, and body mass index (BMI), using clinical data from The Cancer Genome Atlas. We used a Student's t-test to compare age and BMI in groups with different sexes. STATISTICAL ANALYSIS USED: The Kaplan-Meier method with log-rank test was used to determine clinical prognosis. RESULTS: The BMI (30.15 vs. 26.68, P = 0.0035) and age (67.54 years vs. 66.01 years, P = 0.045) of female patients with muscle-invasive bladder cancer (MIBC) were higher than those of male patients. The overall survival (OS) prognosis of female patients was worse than that of male patients. After grouping by disease characteristics, the disease-free survival (DFS) and OS prognoses of female patients under 60 years of age were worse than those of male patients. In the group with BMI >24, the OS prognosis of female patients was worse than that of male patients, but no difference was found in DFS prognosis. In the group with BMI ≤24, the DFS prognosis of female patients was worse than that of male patients, but no difference was found in OS prognosis. Compared to males, female patients with Stage III disease demonstrated a worse DFS prognosis and poorer OS prognosis, women with stage T3 demonstrated a worse DFS prognosis, and women with stage N0 demonstrated a poorer OS prognosis. No difference was found in prognosis between male and female patients in all other groups. CONCLUSIONS: In patients with MIBC, women tended to exhibit a worse prognosis than men. More specifically, we found a correlation between prognosis and sex after grouping patients by BMI.

High IL-22RA1 gene expression is associated with poor outcome in muscle invasive bladder cancer.

BACKGROUND: The cell surface interleukin 22 (IL-22) receptor complex is mainly expressed in epithelial and tissue cells like pancreatitis cells. Recent studies described that IL-22R was overexpressed in malignant diseases and was associated with a poor overall survival (OS). The role of IL-22RA1 gene expression in muscle invasive bladder cancer (MIBC) has not been investigated, yet. OBJECTIVES: The aim of this study was to analyze the role of IL-22RA1 gene expression in patients with MIBC. METHODS: In a cohort of 114 patients with MIBC who underwent radical cystectomy, IL-22RA1 gene expression was analyzed with qRT-PCR and correlated with clinical parameters. Furthermore, Kaplan-Meier and Cox regression analysis were performed. For validation, an in silico dataset (TCGA 2017, n=407) was reanalyzed. RESULTS: IL-22RA1 gene expression was independent of clinicopathological parameters like age (P=0.2681), T stage (P=0.2130), nodal status (P=0.3238) and lymph vascular invasion (LVI, P=0.5860) in patients with MIBC. A high expression of IL-22RA1 was associated with a shorter OS (P=0.0040) and disease-specific survival (P=0.0385). Furthermore, a shorter disease-free survival (DFS) was also associated with a high expression of IL-22RA1 (P=0.0102). In the multivariable analysis, IL-22RA1 expression was an independent prognostic predictors regarding OS (P=0.0096, HR=0.48). In the TCGA cohort, IL-22RA1 expression was independent regarding to OS and DFS. CONCLUSION: A high IL-22RA1 gene expression was associated with worse outcome. Furthermore, IL-22RA1 represented an independent predictor regarding OS in our cohort and therefore might be used for risk stratification in patients with MIBC.

A comprehensive molecular characterization of the 8q22.2 region reveals the prognostic relevance of OSR2 mRNA in muscle invasive bladder cancer.

Technological advances in molecular profiling have enabled the comprehensive identification of common regions of gene amplification on chromosomes (amplicons) in muscle invasive bladder cancer (MIBC). One such region is 8q22.2, which is largely unexplored in MIBC and could harbor genes with potential for outcome prediction or targeted therapy. To investigate the prognostic role of 8q22.2 and to compare different amplicon definitions, an in-silico analysis of 357 patients from The Cancer Genome Atlas, who underwent radical cystectomy for MIBC, was performed. Amplicons were generated using the GISTIC2.0 algorithm for copy number alterations (DNA_Amplicon) and z-score normalization for mRNA gene overexpression (RNA_Amplicon). Kaplan-Meier survival analysis, univariable, and multivariable Cox proportional hazard ratios were used to relate amplicons, genes, and clinical parameters to overall (OS) and disease-free survival (DFS). Analyses of the biological functions of 8q22.2 genes and genomic events in MIBC were performed to identify potential targets. Genes with prognostic significance from the in silico analysis were validated using RT-qPCR of MIBC tumor samples (n = 46). High 8q22.2 mRNA expression (RNA-AMP) was associated with lymph node metastases. Furthermore, 8q22.2 DNA and RNA amplified patients were more likely to show a luminal subtype (DNA_Amplicon_core: p = 0.029; RNA_Amplicon_core: p = 0.01). Overexpression of the 8q22.2 gene OSR2 predicted shortened DFS in univariable (HR [CI] 1.97 [1.2; 3.22]; p = 0.01) and multivariable in silico analysis (HR [CI] 1.91 [1.15; 3.16]; p = 0.01) and decreased OS (HR [CI] 6.25 [1.37; 28.38]; p = 0.0177) in RT-qPCR data analysis. Alterations in different levels of the 8q22.2 region are associated with manifestation of different clinical characteristics in MIBC. An in-depth comprehensive molecular characterization of genomic regions involved in cancer should include multiple genetic levels, such as DNA copy number alterations and mRNA gene expression, and could lead to a better molecular understanding. In this study, OSR2 is identified as a potential biomarker for survival prognosis.

Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands.

This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and 'unfit' patients.

Modified Glasgow prognostic score can predict survival of muscle invasive bladder cancer patients after radiotherapy.

In patients with various cancers, modified Glasgow prognostic score (mGPS) before treatment has predicted prognoses after antitumor therapy. This study aimed to assess whether pretreatment mGPS also has predictive value in patients with muscle-invasive bladder cancer (MIBC) after radiotherapy. A retrospective review accumulated 98 consecutive MIBC patients treated with definitive 3D-conformal radiotherapy from January 2011 to December 2016 in a single center. It included cT2-4bN0-3M0 patients with a median age of 79 years (range: 49 to 95 years). Radiotherapy was delivered at 60-66 Gy for bladder cancer. Patients were categorized in terms of their pretreatment serum albumin and C-reactive protein (CRP) values as mGPS_0, mGPS_1, and mGPS_2. Among them, cumulative overall survival (OS) rates were compared by Kaplan-Meier plots with log-rank tests. The number of patients with mGPS_0, mGPS_1, and mGPS_2 were 40, 40, and 18, respectively. The median follow-up time for all patients was 19 months (range: 2-73 months). The 2-year OS rate for all patients was 75.7%. The 2-year OS rates for mGPS_0, mGPS_1, and mGPS_2 were 85.1%, 71.3%, and 60.9%, respectively. Kaplan-Meier curves revealed a significantly higher cumulative OS rate for mGPS_0 compared with mGPS_1 and mGPS_2 (P = 0.003). Using multivariate Cox regression analysis, mGPS_0 and good performance status were associated with favorable OS rates, of which mGPS_0 was more significant (Hazard ratio 2.74, 95% CI 1.30-5.57, P = 0.008). Modified Glasgow prognostic score may be a novel biomarker that can predict survival in patients with MIBC after radiotherapy.

A TP53-Associated Immune Prognostic Signature for the Prediction of Overall Survival and Therapeutic Responses in Muscle-Invasive Bladder Cancer.

Background: TP53 gene mutation is one of the most common mutations in human bladder cancer (BC) and has been implicated in the progression and prognosis of BC. Methods: RNA sequencing data and TP53 mutation data in different populations and platforms were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database to determine and validate a TP53-associated immune prognostic signature (TIPS) based on differentially expressed immune-related genes (DEIGs) between muscle-invasive bladder cancer (MIBC) patients with and without TP53 mutations. Results: A total of 99 DEIGs were identified based on TP53 mutation status. TIPS including ORM1, PTHLH, and CTSE were developed and validated to identify high-risk prognostic group who had a poorer prognosis than low-risk prognostic group in TCGA and GEO database. The high-risk prognostic group were characterized by a higher abundance of regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages than the low-risk prognostic group. Moreover, they exhibited a lower abundance of CD56bright NK cells, higher expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2, as well as being more likely to respond to anti-PD-1, and neoadjuvant chemotherapy than the low-risk prognostic group. Based on TIPS and other clinical characteristics, a nomogram was constructed for clinical use. Conclusion: TIPS derived from TP53 mutation status is a potential prognostic signature or therapeutic target but additional prospective studies are necessary to confirm this potential.

The Impact of Radiotherapy Facility Volume on the Survival and Guideline Concordance of Patients With Muscle-invasive Bladder Cancer Receiving Bladder-preservation Therapy.

OBJECTIVES: Higher facility surgical volume predicts for improved outcomes in patients with muscle-invasive bladder cancer (MIBC) who undergo radical cystectomy. We investigated the association between facility radiotherapy (RT) case volume and overall survival (OS) for patients with MIBC who received bladder-preserving RT, and the relationship with adherence to National Comprehensive Cancer Network (NCCN) guidelines for bladder preservation. METHODS: The National Cancer Database was used to identify patients diagnosed with nonmetastatic MIBC from 2004 to 2015 and received RT at the reporting center. Facility case volume was defined as the total MIBC patients treated with RT during the period. Facilities were stratified into high-volume facility (HVF) or low-volume facility at the 80th percentile of RT case volume. OS was assessed using Kaplan-Meier analysis. Rates of compliance with NCCN guidelines regarding the use of transurethral resection of the bladder tumor before RT, planned use of concurrent chemotherapy, and total RT dose were compared. Cox proportional hazard model was used to evaluate predictors of OS. RESULTS: There were 7562 patients included. No differences in age, Charlson-Deyo score, T stage, or node-positive rates were observed between groups. HVFs exhibited greater compliance with NCCN guidelines for bladder preservation (P<0.0001). Treatment at an HVF was associated with the improved OS for all patients (P=0.001) and for the subset of patients receiving NCCN-recommended RT doses (P=0.0081). Volume was an independent predictor of OS (P=0.002). CONCLUSIONS: Treatment at an HVF is associated with improved OS and greater guideline-concordant management among patients with MIBC.

Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes.

BACKGROUND: Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC). OBJECTIVES: To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients. DESIGN, SETTING, AND PARTICIPANTS: The study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2-T4N0M0 bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses. RESULTS AND LIMITATIONS: The median TTC was 7.57wk (interquartile range 5.2-10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of <1 (p=0.027). The group with TTC >10wk had significantly lower OM-free (p=0.003) and CSM-free rates (p<0.001) than the group with TTC ≤10wk. TTC was independently associated with higher risk of OM (p=0.027) and CSM (p=0.004) after accounting for age, gender, pathologic extravesical disease, and nodal status. CONCLUSIONS: TTC of >10wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC. PATIENT SUMMARY: The impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

Minimal extrathyroidal extension affects the prognosis of differentiated thyroid cancer: Is there a need for change in the AJCC classification system?

Minimal extrathyroidal extension (ETE) is defined as tumor cells extending to the sternothyroid muscle or perithyroidal soft tissue. However, there is controversy regarding whether the magnitude of ETE (minimal or gross) should be considered in assigning a precise TNM stage to patients with thyroid cancer in the seventh/eighth editions of the AJCC system. The present study evaluated Surveillance, Epidemiology, and End Results data from 107,114 patients with differentiated thyroid cancer (2004-2013) to determine whether the magnitude of ETE (thyroid confinement, minimal, or gross) influenced the ability to predict cancer-specific survival (CSS) and overall survival (OS). Patient mortality was evaluated using Cox proportional hazards regression analyses and Kaplan-Meier analyses with log-rank tests. The cancer-specific mortality rates per 1,000 person-years were 1.407 for the thyroid confinement group (95% CI: 1.288-1.536), 5.133 for the minimal ETE group (95% CI: 4.301-6.124), and 29.735 for the gross ETE group (95% CI: 28.147-31.412). Relative to the thyroid confinement group, patients with minimal ETE and gross ETE had significantly poorer CSS and OS in the univariate and multivariate analyses (both P<0.001). After propensity-score matching according to age, sex, and race, we found that thyroid confinement was associated with better CSS and OS rates than minimal ETE (P<0.001) and gross ETE (P<0.001). These results from a population-based cohort provide a reference for precise personalized treatment and management of patients with minimal ETE. Furthermore, it may be prudent to revisit the magnitude of ETE as advocated by the AJCC and currently used for treatment recommendation by the American Thyroid Association.

Survival after radiotherapy versus radical cystectomy for primary muscle-invasive bladder cancer: A Swedish nationwide population-based cohort study.

BACKGROUND: Studies of survival comparing radical cystectomy (RC) and radiotherapy for muscle-invasive bladder cancer have provided inconsistent results and have methodological limitations. The aim of the study was to investigate risk of death after radiotherapy as compared to RC. METHODS: We selected patients with muscle-invasive urothelial carcinoma without distant metastases, treated with radiotherapy or RC from 1997 to 2014 in the Bladder Cancer Data Base Sweden (BladderBaSe) and estimated absolute and relative risk of bladder cancer death and all-cause death. In a group of patients, theoretically eligible for a trial comparing radiotherapy and RC, we calculated risk difference in an instrumental variable analysis. We have not investigated chemoradiotherapy as this treatment was not used in the study time period. RESULTS: The study included 3 309 patients, of those 17% were treated with radiotherapy and 83% with RC. Patients treated with radiotherapy were older, had more advanced comorbidity, and had a higher risk of death as compared to patients treated with RC (relative risks of 1.5-1.6). In the "trial population," all-cause death risk difference was 6 per 100 patients lower after radiotherapy at 5 years of follow-up, 95% confidence interval -41 to 29. CONCLUSION(S): Patient selection between the treatments make it difficult to evaluate results from conventionally adjusted and propensity-score matched survival analysis. When taking into account unmeasured confounding by instrumental variable analysis, no differences in survival was found between the treatments for a selected group of patients. Further clinical studies are needed to characterize this group of patients, which can serve as a basis for future comparison studies for treatment recommendations.

Tumour expressions of hypoxic markers predict the response to neo-adjuvant chemotherapy in children with inoperable rhabdomyosarcoma.

Objective: The study was to assess whether tumour expressions of hypoxia-inducible factor (HIF)-1α, glucose transporter (GLUT)-1, carbonic anhydrase (CA) IX and vascular endothelial growth factor (VEGF) predict response to neo-adjuvant chemotherapy (naCHT) in children with inoperable rhabdomyosarcoma (RMS). Methods: Immunohistochemical expressions of hypoxia markers were determined semi-quantitatively in tumour tissue microarray of 46 patients with embryonal RMS (RME) and 20 with alveolar (RMA), treated with CWS protocols (1992-2013). Results: In paediatric RME, response to naCHT was influenced significantly by tumour expression of CA IX and GLUT-1. Patients with RMA with low expressions of analysed markers responded well to naCHT, while all poor-responders expressed highly hypoxia markers. Only 5.88% of RMA and 11.11% of RME tumours did not express any of the proteins. In both RME and RMA subgroups, most poor-responders demonstrated simultaneous high expression of ≥3 markers, while most patients expressing ≤2 markers responded well to naCHT. In the whole cohort, co-expression of ≥3 markers, was the only independent factor predicting poor-response to chemotherapy (odds ratio 14.706; 95% CI 1.72-125.75; p = 0.014). Conclusions: Immunohistochemical expression pattern of four endogenous markers of hypoxia, in tumour tissue at diagnosis, emerges as a promising tool to predict response to naCHT in children with inoperable RMS.

Outcomes of surgery and/or combination chemotherapy for extraskeletal osteosarcoma: a single-center retrospective study from China.

Extraskeletal osteosarcoma (ESOS) is an extremely rare malignancy with poor prognosis, accounting for 2-4% of all osteogenic sarcomas. The purpose of this study was to examine the oncological outcomes of this disease related to surgical treatment and/or combined adjuvant therapies and to analyze the associated prognostic factors in ESOS. From January 1990 to June 2016, 22 patients with primary ESOS were analyzed in this retrospective study. Overall survival (OS) and progression-free survival (PFS) rates were calculated by Kaplan-Meier methods and compared with log-rank test. 22 patients were diagnosed with ESOS, 19 showed localized diseases and 3 presented with metastatic lesions. The median age at diagnosis was 55.5 years. Surgery resection was performed for all patients, 18 of whom received adjuvant chemotherapy. The median follow-up time was 48.5 months. There were 10 cases of recurrence and 9 patients developed new metastases. The 5-year OS rate for all patients was 58%. For localized cohort, the 5-year OS rate was 62%, and the 3-year PFS rate was 31% with a median PFS of 16 months. Univariate analysis of related prognosis factors showed that larger size of tumor (>5.5 cm) and higher histologic grade emerged as significant factors associated with worse OS. The addition of combination chemotherapy has no effect found on OS or PFS in this study. In summary, for patients who presented with ESOS, larger tumor size and higher histologic grade indicate a lower OS rate. The combination chemotherapy does not improve the OS or PFS.

Contemporary Survival Rates for Muscle-Invasive Bladder Cancer Treated With Definitive or Non-Definitive Therapy.

INTRODUCTION: Definitive, curatively intended therapy for muscle-invasive bladder cancer can be associated with significant morbidity and adverse effects on quality of life, leaving patients reluctant to opt for these interventions. We sought to provide perspective to patients and clinicians exploring therapy options. MATERIALS AND METHODS: We examined stage-by-stage overall survival of definitive therapy (DT) (either radical cystectomy in conjunction with neoadjuvant chemotherapy or trimodal therapy) versus non-DT (including palliative transurethral resection, chemotherapy and radiation treatment) among 42,144 patients within the National Cancer Database (2004-2012). RESULTS: The median overall survival stratified by receipt of DT versus non-DT was 45.3 versus 16.4 months, 26.7 versus 9.6 months, and 21.2 versus 7.5 months in American Joint Committee on Cancer stages II, III, and IV, respectively. In multivariable Cox regression analysis, DT conferred a significant survival benefit in all stages, most pronounced in American Joint Committee on Cancer stage IV (hazard ratio, 0.46; 95% confidence interval, 0.43-0.49; P < .001). CONCLUSION: Despite potentially significant morbidity and adverse effects on quality of life, DT is associated with a sizable survival benefit.

Delays in radical cystectomy for muscle-invasive bladder cancer.

BACKGROUND: Delays from the diagnosis of muscle-invasive bladder cancer (MIBC) to radical cystectomy (RC) longer than 12 weeks result in higher mortality and shorter progression-free survival. This study sought to identify factors associated with RC delays and to determine whether delays in care in the current treatment paradigm, which includes neoadjuvant chemotherapy (NAC), affect survival. METHODS: Subjects with American Joint Committee on Cancer stage II urothelial carcinoma of the bladder who underwent RC from 2004 to 2012 were identified from the linked Surveillance, Epidemiology, and End Results national cancer registry and the Medicare claims database and were stratified into RC groups with or without NAC. Cox multivariable proportional hazard models and multivariable logistic regression models assessed the significance of delays in RC for survival and identified independent characteristics associated with RC delays, respectively. RESULTS: This study identified 1509 patients with MIBC who underwent RC during the study period. In comparison with timely surgery, delays in RC increased overall mortality, regardless of the use of NAC (hazard ratio [HR] without NAC, 1.34; 95% confidence interval [CI], 1.03-1.76; HR after NAC, 1.63; 95% CI, 1.06-2.52). Patients proceeding to RC without NAC had higher odds of delayed care if they lived in a high-poverty neighborhood (odds ratio [OR], 1.37; 95% CI, 1.01-2.08) or nonmetropolitan area (OR, 1.61; 95% CI, 1.01-2.55), were men (OR, 2.22; 95% CI, 1.25-4.00), or required a provider transfer for bladder cancer care (OR, 1.82; 95% CI, 1.10-3.03). CONCLUSIONS: Delays in care from the time of either the initial diagnosis or the completion of NAC to RC are associated with worse overall survival among patients with MIBC. Timely surgery is fundamental in the treatment of MIBC, and this necessitates attention to disparities in access to complex surgical care and care coordination.

Neoadjuvant Chemotherapy Before Bladder-Sparing Chemoradiotherapy in Patients With Nonmetastatic Muscle-Invasive Bladder Cancer.

BACKGROUND: Cisplatin-based neoadjuvant chemotherapy (NAC) before cystectomy improves survival in muscle-invasive urothelial bladder cancer (MIBC). The use of NAC before chemoradiation (CRT) has been limited, as these patients are often elderly, frail, and ineligible for cisplatin. However, the role of NAC in fit, cisplatin-eligible patients who opt for bladder preservation warrants further evaluation. PATIENTS AND METHODS: Patients with MIBC treated with NAC followed by CRT at the Princess Margaret and Durham Regional cancer centers from 2008 to 2017 were retrospectively reviewed. Gemcitabine-cisplatin NAC was given for 2 to 4 cycles, followed by reassessment for CRT. External-beam radiotherapy (60-66 Gy) over 6 weeks was given with concurrent weekly cisplatin at 40 mg/m2. Kaplan-Meier method was used for survival analyses. RESULTS: We identified 57 consecutive patients. Median age was 72 (range 45-87), and all had an Eastern Cooperative Oncology Group performance status of 0 (60%) or 1 (40%). Stage II disease (65%), stage III disease (25%), and regional nodal metastases (11%) were included. Most completed planned NAC (95%). All patients completed external-beam radiotherapy, and 84% completed at least 60% of the planned concurrent weekly cisplatin doses. Median (range) follow-up was 19.3 (4.8-96.1) months. Median overall survival (OS) was not reached. Two-year OS and disease-specific survival rates were 74% (95% confidence interval, 57.7-84.9) and 88% (95% confidence interval, 78.5-98.1), respectively. Two-year bladder-intact disease-free survival was 64%. Salvage cystectomy was performed in 14%. Distant relapse occurred in 11%, and 9% died of metastatic disease. OS was associated with baseline hydronephrosis and with bladder-intact disease-free survival with residual disease on cystoscopy. CONCLUSION: NAC followed by CRT can result in encouraging outcomes and tolerability in cisplatin-eligible patients.

Impact of adjuvant chemotherapy in patients with adverse features and variant histology at radical cystectomy for muscle-invasive carcinoma of the bladder: Does histologic subtype matter?

BACKGROUND: The use of adjuvant chemotherapy (AC) in pure urothelial carcinoma of the bladder is established. Regarding variant histology, there is a gap in knowledge concerning the optimal treatment after radical cystectomy (RC). The objective of this study was to assess the effect of AC on overall survival (OS) in patients who had pure urothelial carcinoma, urothelial carcinoma with concomitant variant histology, or another pure variant histology. METHODS: Within the National Cancer Data Base, 15,397 patients who underwent RC for nonmetastatic, localized carcinoma of the bladder and had positive lymph nodes (T2N+) or locally advanced stage (≥T3N0/N+) were identified, excluding those who had previously received neoadjuvant chemotherapy. Multivariable Cox regression models were used to examine the specific effect of AC on OS stratified by each distinct histologic subtype, including pure urothelial carcinoma, micropapillary or sarcomatoid differentiation, squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. To account for immortal time bias, Cox regression analyses and Kaplan-Meier analyses were conducted with a landmark at 3 months. RESULTS: In multivariable landmark analyses, AC compared with initial observation was associated with an OS benefit for patients who had pure urothelial carcinoma (hazard ratio, 0.87; 95% confidence interval, 0.82-0.91), whereas no differences were observed with regard to those who had variant histology. CONCLUSIONS: Multivariable Cox regression landmark analysis revealed a survival benefit from AC for patients with a pure urothelial carcinoma. However, a survival benefit of AC for patients who had urothelial carcinoma with concomitant variant histology or other pure variant histology was not demonstrated.

Comparative Effectiveness of Bladder-preserving Tri-modality Therapy Versus Radical Cystectomy for Muscle-invasive Bladder Cancer.

INTRODUCTION: There are limited randomized data comparing radical cystectomy (RC) with bladder-sparing tri-modality therapy (TMT) in the treatment of muscle-invasive bladder cancer (MIBC). Both strategies are thought to have similar survival outcomes with different morbidity profiles. We compare the effectiveness of TMT and RC using decision-analytic modeling and the endpoint of quality-adjusted life years (QALYs). PATIENTS AND METHODS: Using a Markov model, we simulated the lifetime outcomes after TMT versus RC ± neoadjuvant chemotherapy for 67-year-old patients with clinical stage T2-T4aN0M0 MIBC. Model probabilities and utilities were extracted from the literature. The incremental effectiveness was reported in QALYs and sensitivity analyses were performed. RESULTS: For all patients with MIBC, although the model showed identical survival, TMT was the most effective strategy with an incremental gain of 0.59 QALYs over RC (7.83 vs. 7.24 QALYs, respectively). When limiting the model to favorable, contemporary cohorts in both the TMT and RC strategies, TMT remained more effective with an incremental gain of 1.61 QALYs (9.37 vs. 7.76 QALYs, respectively). One-way sensitivity analyses demonstrated the model was sensitive to the quality of life parameters (ie, the utilities) for RC and TMT. When testing the 95% confidence interval of the RC utility parameter the model demonstrated an incremental gain with TMT from -0.54 to 4.23 QALYs. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 63% of model iterations. CONCLUSIONS: This modeling study found that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of QALYs relative to RC.

The expression profile of p14, p53 and p21 in tumour cells is associated with disease-specific survival and the outcome of postoperative chemotherapy treatment in muscle-invasive bladder cancer.

PURPOSE: We investigated the effects of alterations in the biological markers p14, p53, p21, and p16 in relation to tumour cell proliferation, T-category, N- category, lymphovascular invasion, and the ability to predict prognosis in patients with muscle-invasive bladder cancer (MIBC) treated with cystectomy and, if applicable, chemotherapy. MATERIALS AND METHODS: We prospectively studied patients with urinary bladder cancer pathological stage pT1 to pT4 treated with cystectomy, pelvic lymph node dissection and postoperative chemotherapy. Tissue microarrays from paraffin-embedded cystectomy tumour samples were examined for expression of immunostaining of p14, p53, p21, p16 and Ki-67 in relation to other clinical and pathological factors as well as cancer-specific survival. RESULTS: The median age of the 110 patients was 70 years (range 51-87 years), and 85 (77%) were male. Pathological staging was pT1 to pT2 (organ-confined) in 28 (25%) patients and pT3 to pT4 (non-organ-confined) in 82 (75%) patients. Lymph node metastases were found in 47 patients (43%). P14 expression was more common in tumours with higher T-stages (P = 0.05). The expression of p14 in p53 negative tumours was associated with a significantly shorter survival time (P=0.003). Independently of p53 expression, p14 expression was associated with an impaired response to chemotherapy (P=0.001). The expression of p21 in p53 negative tumours was associated with significantly decrease levels of tumour cell proliferation detected as Ki-67 expression (P=0.03). CONCLUSIONS: The simultaneous expression of the senescence markers involved in the p53-pathway shows a more relevant correlation to the pathological outcome of MIBC than each protein separately. P14 expression in tumours with non-altered (p53-) tumours is associated with poor prognosis. P14 expression is associated with impaired response to chemotherapy. P21 expression is related to decreased tumour cell proliferation.

Ten-year Survival Rates for Women of Grand Bahama Island, The Bahamas, Diagnosed with Breast Cancer in 1988-2002 / Tasas de diez años de supervivencia en las mujeres de Gran Bahama, Bahamas, diagnosticadas con cáncer de mama en 1988-2002

ABSTRACT A total of 150 women from Grand Bahama Island, The Bahamas, with cancer of the breast were followed up for 10 years post-diagnosis to assess survival rates, not only generally, but also by age and stage of disease at diagnosis, the presence or absence of axillary lymph node metastases, the treatment modalities received, and the diagnostic periods. The patients' medical records and the death registers of the Medical Records Department of Rand Memorial Hospital (RMH), Grand Bahama Island, supplemented with data from the ledgers of the Pathology Department of RMH and from The Bahamas ' national death register, were utilized. By Pearson Chi-square and Kaplan-Meier survival analysis, females who were 40 years old or younger lived significantly longer (71.2% of whom for at least 10 years; mean: 213.8 months) than those who were older than 40 years (42.9% of whom for at least 10 years; mean: 167.9 months). The absence or presence of axillary lymph node metastases also had a bearing on survival, with 71.9% surviving at least 10 years (mean: 243.9 months) versus 32.7% (mean: 108.1 months) respectively. Despite the accepted importance of the diagnostic stage of disease, the small sample size obtained allowed only a limited assessment of the influence of staging on the survival rates. Neither the treatment received nor the diagnostic periods had any significant influence on the survival rates. The establishment of a national cancer registry in The Bahamas would alleviate the problems due to retrieval of information and aid in the better management and follow-up of cancer. Because of a relatively young age at diagnosis, consideration must also be given to beginning mammography screening of Bahamian women at an age below 40 years.

RESUMEN Un total de 150 mujeres con cáncer de mama en Gran Bahama, Bahamas, recibieron un seguimiento de 10 años después del diagnóstico, a fin de evaluar las tasas de supervivencia. La evaluación de las tasas de supervivencia se realizó no sólo de manera general, sino también sobre la base de la edad y etapa de la enfermedad en el momento del diagnóstico, la presencia o ausencia de metástasis en los ganglios axilares, las modalidades de tratamiento recibidas, y los períodos de diagnóstico. A tal fin, se utilizaron las historias clínicas de los pacientes y los registros de defunción existentes en el Departamento de Historias Clínicas del Hospital Rand Memorial (HRM) de Gran Bahama, complementados con datos provenientes de los libros de archivo del Departamento de Patología de HRM y el Registro Nacional de Defunciones de Bahamas. Según el análisis de la supervivencia mediante Pearson Chi-Square y Kaplan-Meier, las mujeres de 40 años o más jóvenes vivieron significativamente más tiempo (71.2% de ellas por lo menos diez años; promedio: 213.8 meses) que las mayores de 40 años (42.9% de ellas por lo menos diez años; promedio: 167.9 meses). La ausencia o presencia de metástasis en los ganglios axilares también tuvo una incidencia en la supervivencia, sobreviviendo el 71.9% por lo menos 10 años (promedio: 243.9 meses) frente a un 32.7% (promedio: 108.1 meses) respectivamente. A pesar de la reconocida importancia de la etapa diagnóstica de la enfermedad, el pequeño tamaño de la muestra obtenida permitió sólo una evaluación limitada de la influencia de la estadificación en las tasas de supervivencia. Ni el tratamiento recibido ni los periodos de diagnóstico tuvieron influencia significativa en las tasas de supervivencia. El establecimiento de un registro nacional del cáncer en las Bahamas aliviaría los problemas relacionados con la recuperación de información y ayudaría a un mejor tratamiento y seguimiento del cáncer. Debido a la edad relativamente joven en que realiza el diagnóstico, debe considerarse también comenzar la investigación de la mamografia de las mujeres de las Bahamas antes de los 40 años.