The Impact of the Extent of Lymphadenectomy on Oncologic Outcomes in Patients Undergoing Radical Cystectomy for Bladder Cancer : A Systematic Review

Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewedPostprin

Intracutaneous and intravesical immunotherapy with keyhole limpet hemocyanin compared with intravesical mitomycin in patients with non-muscle-invasive bladder cancer: results from a prospective randomized phase III trial.

Contains fulltext : 108422.pdf (publisher's version ) (Open Access)PURPOSE: Despite current treatment after transurethral resection of a bladder tumor, recurrences and progression remain a problem. Keyhole limpet hemocyanin (KLH) was beneficial in earlier studies. In this study, safety and efficacy of KLH were compared with that of mitomycin (MM). PATIENTS AND METHODS: Patients with intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) without carcinoma in situ were enrolled in a randomized phase III trial. In all, 283 patients were randomly assigned for 16 adjuvant intravesical instillations with KLH after preimmunization, and 270 patients were randomly assigned for 11 adjuvant intravesical instillations with MM. Primary outcome measurement was recurrence-free survival (RFS). Secondary outcome measurements were progression-free survival, adverse events (AEs), and the effect of delayed-type hypersensitivity (DTH) response on clinical outcome. RESULTS: There were significantly more pT1 tumors in the MM group (P = .01). In a log-rank test, univariate and multivariate Cox regression analysis, KLH was less effective than MM regarding RFS (all P < .001). Progression was uncommon (n = 20). In univariate Cox regression analyses, KLH tended to prevent progression more effectively than MM, but in multivariate Cox regression analyses, this could not be shown. AEs were common but mild. Fever, flu-like symptoms, and fatigue occurred significantly more after KLH treatment. Allergic reactions and other skin disorders occurred significantly more after MM treatment. Significantly more DTH-positive patients developed a recurrence than DTH-negative patients. CONCLUSION: KLH had a different safety profile and was inferior to MM in preventing NMIBC recurrences. KLH tended to be more effective than MM in preventing progression. More research is needed to clarify the immunologic effects of KLH and the effects of KLH on progression

The Doctor in Literature. Volume 4. Gender and Sex

This book is the fourth of four volumes in the series The Doctor in Literature. Like the first three it is intended to serve as an indexed, annotated anthology and to bring together a total of some 1500 extracts from approximately 600 works of fiction where medical doctors appear as major or minor characters. The citations in volume 4 relate to sex and gender as these issues affect physicians and medical practice, There is a lengthy chapter discussing fictional female doctors and the perceived differences between these women and their male colleagues. Nurses (generally female) and their interactions with doctors (generally male) are discussed in three chapters. Sexual encounters between patients and doctors form the subject of the last chapter

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer

Purpose: To evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC). Patients and methods: In this nationwide, Netherlands Cancer Registry-based study, we identified 1025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0–1 and creatinine clearance ≥ 50 mL/min/1.73 m2 were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a). Results: In total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7–57% and 31–62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HRcT2 = 0.59, 95% CI 0.33–1.05 and HRcT3-4a = 0.71, 95% CI 0.25–2.04). Conclusion: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.</p

Risk of Progression of High-grade Primary T1 Non-muscle-invasive Bladder cancer in a Contemporary Cohort

Patients with high-risk non–muscle-invasive bladder cancer (NMIBC) receive bacillus Calmette-Guérin (BCG) instillations to reduce the risk of progression. For patients with very high-risk NMIBC, immediate radical cystectomy may be considered, as patients who experience disease progression despite BCG treatment have a worse prognosis. However, guideline-recommended stratification for the risk of progression is based on data from patients who were not exposed to BCG. We evaluated the risk of progression in a contemporary cohort of patients with primary high-grade/grade 3 (HG/G3) T1 NMIBC (n = 1268) who received at least one BCG instillation and underwent at least one cystoscopic evaluation. The primary endpoint was the 1-yr risk of progression for all patients and for the subgroup that received adequate BCG, defined as at least five induction instillations and at least two instillations provided as a second BCG course within 6 mo. Progression was defined as detrusor muscle invasion or lymph node or distant metastasis. The 1-yr risk of progression was 6.5% (95% confidence interval [CI] 5.2-8.0) for patients with primary HG/G3 T1 NMIBC who started BCG treatment, and 4.6% (95% CI 3.3–6.4) 1 yr after the first instillation of the second BCG course for patients who received adequate BCG (n = 746). In conclusion, the contemporary risk of progression for patients with HG/G3 T1 NMIBC who receive BCG appears to be low, especially for patients who receive adequate BCG treatment

Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer

Purpose: To evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC). Patients and methods: In this nationwide, Netherlands Cancer Registry-based study, we identified 1025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0–1 and creatinine clearance ≥ 50 mL/min/1.73 m2 were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a). Results: In total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7–57% and 31–62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HRcT2 = 0.59, 95% CI 0.33–1.05 and HRcT3-4a = 0.71, 95% CI 0.25–2.04). Conclusion: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.</p

Randomized Phase Iii Study Comparing Paclitaxel-bleomycin, Etoposide, And Cisplatin (bep) To Standard Bep In Intermediate-prognosis Germ-cell Cancer: Intergroup Study Eortc 30983

Purpose: To compare the efficacy of four cycles of paclitaxel-bleomycin, etoposide, and cisplatin (T-BEP) to four cycles of bleomycin, etoposide, and cisplatin (BEP) in previously untreated patients with intermediate-prognosis germ-cell cancer (GCC). Patients and Methods: Patients were randomly assigned to receive either T-BEP or standard BEP. Patients assigned to the T-BEP group received paclitaxel 175 mg/m(2) in a 3-hour infusion. Patients who were administered T-BEP received primary granulocyte colony-stimulating factor (G-CSF) prophylaxis. The study was designed as a randomized open-label phase II/III study. To show a 10% improvement in 3-year progression-free survival (PFS), the study aimed to recruit 498 patients but closed with 337 patients as a result of slow accrual. Results: Accrual was from November 1998 to April 2009. A total of 169 patients were administered BEP, and 168 patients were administered T-BEP. Thirteen patients in both arms were ineligible, mainly as a result of a good prognosis of GCC (eight patients administered BEP; six patients administered T-BEP) or a poor prognosis of GCC (one patient administered BEP; four patients administered T-BEP). PFS at 3 years (intent to treat) was 79.4% in the T-BEP group versus 71.1% in the BEP group (hazard ratio [HR], 0.73; CI, 0.47 to 1.13; P [log-rank test] = 0.153). PFS at 3 years in all eligible patients was 82.7% versus 70.1%, respectively (HR, 0.60; CI: 0.37 to 0.97) and was statistically significant (P = 0.03). Overall survival was not statistically different. Conclusion: T-BEP administered with G-CSF seems to be a safe and effective treatment regimen for patients with intermediate-prognosis GCC. However, the study recruited a smaller-than-planned number of patients and included 7.7% ineligible patients. The primary analysis of the trial could not demonstrate statistical superiority of T-BEP for PFS. When ineligible patients were excluded, the analysis of all eligible patients demonstrated a 12% superior 3-year PFS with T-BEP, which was statistically significant. J Clin Oncol 30: 792-799. (C) 2012 by American Society of Clinical Oncolog

The impact of positive surgical margins after cystectomy on oncological outcomes:a nationwide study

Objective:To evaluate whether surgical margin status, alongside existing postoperative risk indicators, improves the identification of bladder cancer patients who may benefit from adjuvant therapy following radical cystectomy (RC).Methods:In this nationwide cohort study, patients aged &gt;= 18 years diagnosed with muscle-invasive bladder cancer (MIBC) without nodal or distant metastasis (cT2-4aN0/xM0) between November 2017 and December 2020 who underwent RC were selected from the Netherlands Cancer Registry. Detailed information on surgical margin status was obtained through linkage with the Dutch central pathology database, Palga. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. Multivariable Cox regression analysis was performed to assess the independent prognostic effect of positive surgical margins (carcinoma in situ (CIS)] only or invasive carcinoma) on PFS and OS.Results:We identified 1445 MIBC patients treated by RC (53% open, 47% robot-assisted), of whom 135 (9.3%) had positive surgical margins (10.7% in the open and 7.7% in the robot-assisted cohort). In the entire cohort, OS was 79% and 60% at 12 and 48 months after RC, respectively. PFS was 70% and 61% at 12 and 24 months, respectively. Multivariable Cox regression showed worse PFS (hazard ratio (HR) 2.13, 95% confidence interval (CI) 1.67-2.72) and OS (HR 2.02, 95% CI 1.58-2.58) in patients with surgical margins with invasive carcinoma vs patients with negative margins. Patients with only CIS in the margins also appeared to have worse PFS (HR 1.60, 95% CI 1.00-2.58) but these results were not statistically significant. No difference was found for OS (HR 1.30, 95% CI 0.80-2.12).Conclusion:Positive margins should be considered a 'high risk feature, as they result in increased risk of disease progression and impaired survival outcomes. These findings support further investigation of the potential efficacy of adjuvant therapy (i.e., radiotherapy and systemic therapy) among patients with positive surgical margins

Minimum Volume Standards: An Incentive To Perform More Radical Cystectomies?

Background: Minimum volume standards (MVS) for hospitals and/or surgeons remain a subject of debate. Opponents of MVS emphasize the possible negative effects of centralization, such as an unwanted incentive to perform surgery. Objective: To evaluate whether the introduction of MVS for radical cystectomy (RC) in the Netherlands resulted in more RCs outside guideline-recommended indications. Design, setting, and participants: All RCs performed for bladder cancer in the Netherlands between January 1, 2006 and December 31, 2017 were identified in the Netherlands Cancer Registry. During this period, two MVS were sequentially implemented for RC. RCs in intermediate-volume hospitals (hospitals that approximated the MVS) were compared with RCs in high-volume hospitals (hospitals exceeding the MVS by ≥5 RCs/yr) in a period before and a period after implementation of each of the two MVS. Outcomes measurements and statistical analysis: Descriptive analyses were performed to evaluate whether hospitals performed more RCs outside the recommended indication (cT2–4a N0 M0) and whether an increase in the number of RCs towards the end of the year could be observed. Results and limitations: After MVS implementation, no clear shift towards disease stages outside the recommended indication for RC was observed in comparison to the period before the MVS. Results for high-volume and intermediate-volume hospitals were similar. In addition, no increase in RCs towards the end of the year was evident. Conclusions: We did not find evidence indicating an unwanted incentive to perform more RCs as a result of MVS in the Netherlands. Our results further strengthen the case for MVS implementation. Patient summary: We evaluated whether criteria for the minimum number of radical cystectomies (surgical removal of the bladder) that hospitals have to perform caused urologists to perform more of these operations than necessary in order to meet the minimum level. We found no evidence that minimum criteria led to such an unwanted incentive