Association between early change in neutrophil-to-lymphocyte ratio after radical cystectomy and treatment outcomes.

OBJECTIVES: To evaluate the associations of peri-operative neutrophil-to-lymphocyte ratio (NLR) and change in NLR with survival after radical cystectomy. PATIENTS AND METHODS: We retrospectively reviewed a multicentre cohort of patients with bladder cancer who underwent radical cystectomy between 2010 and 2020. Preoperative NLR, postoperative NLR, delta-NLR (postoperative minus preoperative NLR) and NLR change (postoperative divided by preoperative NLR) were calculated. Patients were stratified based on elevation of preoperative and/ or postoperative NLR above the median values. Multivariable Cox regression models were used to evaluate the associations of peri-operative NLR and NLR change with survival. RESULTS: The study cohort included 346 patients with a median age of 69 years. The median (interquartile range) preoperative NLR, postoperative NLR, delta-NLR and NLR change were 2.55 (1.83, 3.90), 3.33 (2.21, 5.20), 0.43 (-0.50, 2.08) and 1.2 (0.82, 1.96), respectively. Both preoperative and postoperative NLR were elevated in 110 patients (32%), 126 patients (36%) had an elevated preoperative or postoperative NLR, and 110 patients (32%) did not have an elevated NLR. On multivariable analysis, increased preoperative and postoperative NLR were significantly associated with decreased survival. While delta-NLR and NLR change were not associated with outcome, patients with elevations in both preoperative and postoperative NLR had the worst overall (hazard ratio [HR] 2.97, 95% confidence interval [CI] 1.78, 4.95; P < 0.001) and cancer-specific survival rates (HR 2.41, 95% CI 1.3, 4.4; P = 0.004). CONCLUSIONS: Preoperative and postoperative NLR are significant predictors of survival after radical cystectomy; patients in whom both NLR measures were elevated had the worst outcomes. Future studies should evaluate whether an increase in NLR during long-term follow-up may precede disease recurrence.

Shock Wave Lithotripsy in Pediatric Stone Disease: A 15-Year Single-Center Experience with 2 Types of Lithotripters.

INTRODUCTION AND OBJECTIVES: We report our experience with pediatric shock wave lithotripsy (SWL) using two types of lithotripters: Dornier HM3 (HM3) and Dornier Lithotripter SII (DLS). STUDY DESIGN: We retrospectively reviewed the charts of children who underwent SWL between 2002 and 2016. Patients were divided into two groups based on the type of the lithotripter: during 2002-2009, we used the electrohydraulic HM3 lithotripter which was replaced in 2009 with the DLS electromagnetic lithotripter. Clinical and perioperative parameters were compared. RESULTS: Our cohort included 107 children who underwent SWL. Average age was 11.5 ± 5.1 years. Average stone size was 10.6 ± 4.9 mm. HM3 was used in 38% of children and DLS2 in 62% (n = 41 and 66, respectively). There were no significant differences in age, gender, stone size, or location between the groups. The total SFR did not differ statistically between HM3 and DLS (83% vs. 74%, p = 0.35). SFR after one SWL was higher with the HM3 (78% vs. 62%, p = 0.093). Re-treatment rate was 22% and 17% (HM3 vs. DLS, p = 0.61). Complication rates were low, with renal colic being the most common (HM3 10%, DLS 20%, NS). CONCLUSIONS: SWL in the pediatric population using the DLS showed good results with low complication rates that are equivalent to the gold standard HM3.

Tailoring Antibiotic Prophylaxis for Ureteroscopic Procedures Based on Local Resistance Profiles May Lead to Reduced Rates of Infections and Urosepsis.

INTRODUCTION AND OBJECTIVES: Urinary tract infections (UTI) following ureteroscopy (URS) occur in about 4% of patients. Due to the resistant bacterial strains we encounter in our institution, we retrospectively examined whether a double-drug antibiotic prophylactic treatment (APT) can reduce urosepsis after URS. MATERIALS AND METHODS: Between February 2015 and March 2016, we performed 344 URS for stone treatment. Starting from September 2015, we changed the APT. Exclusion criteria included procedures involving percutaneous nephrolithotomy, pediatric or pregnant patients, and patients with preoperative clinical UTI. RESULTS: Fifty-seven patients were excluded. Group 1 (n = 106) were the last to receive the conventional APT (oral ciprofloxacin), while the second group (n = 181) were the first to receive the new -regimen (intravenous gentamycin and ampicillin). A distinct percentage of both groups had a preoperative positive urine culture (29% in group 1 and 19% in group 2). Seven of 9 septic events developed in patients with preoperative positive urine culture (p < 0.001). Patients undergoing retrograde intrarenal surgery were at increased risk for sepsis when treated with conventional APT (p < 0.01). Post-URS sepsis was 7.5% using the conventional APT and 0.5% with the new APT (p < 0.0001). CONCLUSIONS: A distinct number of patients undergoing URS stone treatment have positive preoperative urine cultures. "One size fits all" APT is not sufficient according to our data. A regimen tailored to the local antibiotic resistance of the uropathogens can lower the rate of sepsis.

External Validation of Bladder Cancer Predictive Nomograms for Recurrence, Cancer-Free Survival and Overall Survival following Radical Cystectomy.

PURPOSE: We externally validated 3 previously published nomograms to predicting recurrence, and cancer specific and overall survival following radical cystectomy and pelvic lymph node dissection for urothelial carcinoma of the bladder. MATERIALS AND METHODS: Two surgeons from a single institution performed a total of 197 consecutive radical cystectomies and pelvic lymph node dissections for bladder cancer from January 2003 to September 2009. A total of 23 patients were excluded from analysis. Examined parameters were those used in the original nomograms, including patient age, gender, pathological T stage, N stage, tumor grade, presence of carcinoma in situ and lymphovascular invasion, neoadjuvant chemotherapy, adjuvant chemotherapy and adjuvant radiation therapy. Nomogram predictions were compared to actuarial outcomes and predictive accuracy was quantified using measures of discrimination and calibration. RESULTS: At the time of analysis 34 patients had experienced recurrence, of whom 28 died of disease and 6 were currently alive with disease. Discrimination at 2, 5 and 8 years was 0.776, 0.809 and 0.794 for recurrence, 0.822, 0.840 and 0.849 for cancer specific survival, and 0.812, 0.820 and 0.825, respectively, for overall survival. Calibration plots revealed nomogram overestimation of all 3 end points. CONCLUSIONS: Nomograms for bladder cancer recurrence, cancer specific survival and overall survival following radical cystectomy and pelvic lymph node dissection performed well in our series with accuracy comparable to that in the original series. The use of nomogram predictions should be further explored in clinical trials to assess the impact on patient care in clinical practice.

Educational opportunities in bladder cancer: increasing cystoscopic adherence and the availability of smoking-cessation programs.

Cancer survivors who continue to smoke following diagnosis are at increased risk for recurrence. Yet, smoking prevalence among survivors is similar to the general population. Adherence to cystoscopic surveillance is an important disease-management strategy for non-muscle-invasive bladder cancer (NMIBC) survivors, but data from Surveillance, Epidemiology, and End Results program (SEER) suggest current adherence levels are insufficient to identify recurrences at critically early stages. This study was conducted to identify actionable targets for educational intervention to increase adherence to cystoscopic monitoring for disease recurrence or progression. NMIBC survivors (n = 109) completed telephone-based surveys. Adherence was determined by measuring time from diagnosis to interview date; cystoscopies received were then compared to American Urological Association (AUA) guidelines. Data were analyzed using non-parametric tests for univariate and logistic regression for multivariable analyses. Participants averaged 65 years (SD = 9.3) and were primarily white (95 %), male (75 %), married (75 %), and non-smokers (84 %). Eighty-three percent reported either Ta- or T1-stage bladder tumors. Forty-five percent met AUA guidelines for adherence. Compared to non-smokers, current smokers reported increased fear of recurrence and psychological distress (p < 0.05). In regression analyses, non-adherence was associated with smoking (OR = 33.91, p < 0.01), providing a behavioral marker to describe a survivor group with unmet needs that may contribute to low cystoscopic adherence. Research assessing survivorship needs and designing and evaluating educational programs for NMIBC survivors should be a high priority. Identifying unmet needs among NMIBC survivors and developing programs to address these needs may increase compliance with cystoscopic monitoring, improve outcomes, and enhance quality of life.

The Impact of PSMA PET/CT on Modern Prostate Cancer Management and Decision Making-The Urological Perspective.

Prostate-specific membrane antigen (PSMA) PET use in prostate cancer treatment has recently become a routinely used imaging modality by urologists. New, established data regarding its performance in different stages of prostate cancer, as well as gaining clinical knowledge with new tracers, drives the need for urologists and other clinicians to improve the utilization of this tool. While the use of PSMA PET/CT is more common in metastatic disease, in which it outperforms classical imaging modalities and drives treatment decisions and adjustments, recently, it gained ground in localized prostate cancer as well, especially in high-risk disease. Still, PSMA PET/CT might reveal lesions within the prostate or possibly locoregional or metastatic disease, not always representing true cancer when utilized in earlier stages of the disease, potentially adding diagnostic burden and changing treatment decisions. As urological treatment options advance toward focal treatments in localized organ-confined prostate cancer, recent reports suggest the utilization of PSMA PET/CT in treatment planning and follow-up and even when choosing active surveillance. This review aims to reveal the current perspective of urologists regarding its daily use.

Urine survivin as a diagnostic biomarker for bladder cancer: a systematic review.

What's known on the subject? and What does the study add? Although many tests for identifying patients with new or recurrent bladder cancer have been used, a reliable method has yet to be established. Recently, increasing attention has focused on the role of survivin in bladder cancer detection. Because urine survivin tests have better sensitivity than cytology, urine survivin could potentially replace routine cytology and might be used as an adjunct method for cystoscopy. However, the clinical utility of urine survivin as a bladder tumour marker identified in the present study remains to be elucidated. To determine the clinical utility of urine survivin as a bladder tumour marker we systematically reviewed the available evidence. A comprehensive literature review was performed, from August 1997 to March 2011, using three search engines in English including PubMed, Cochrane Library, and SCOPUS. Two reviewers independently evaluated both trial eligibility and methodological quality and data extraction. We included studies that evaluated urine survivin, used cystoscopy and/or histopathology as the reference standard, and allowed the construction of a 2 × 2 contingency table. Bivariate random effect meta-analyses were used to calculate the summary estimated of sensitivity and specificity and to construct a summary receiver-operating characteristics curve of urine survivin tests. In all, 14 studies were included in the present review; two studies had two subsets of data. There were 2051 subjects, including 1038 in the case group and 1013 in the control group, and heterogeneity was present among diagnostic studies. The pooled sensitivity and specificity for urine survivin tests were 0.772 (95% confidence interval [CI] 0.745-0.797) and 0.918 (95% CI 0.899-0.934), respectively. The area under the curve of urine survivin tests was 0.9392. When a subgroup analysis with six studies was performed, urine survivin tests had better sensitivity than cytology, but did not match cytology for specificity. The clinical utility of urine survivin as a bladder tumour marker identified in the present study remains to be elucidated.

Racial/ethnic differences in upper-tract urothelial cancer.

OBJECTIVES: Information on clinical characteristics, pattern of initial treatment and survival in patient with upper-tract urothelial carcinomas (UTUC) is scarce. Our study examined the racial/ethnic differences in patients diagnosed with incident UTUC. DESIGN: Observational study. The data analyses included: proportion and ANOVA for categorical and continuous variables, respectively; Kaplan-Meier method for calculating overall survival; and Cox-proportional hazards models for obtaining adjusted hazard-ratios. SETTING: Regions of the Surveillance, Epidemiology and End Results (SEER). PATIENTS OR PARTICIPANTS: 16,702 incident UTUC patients identified from the SEER dataset 1988-2007 (14,192 White, 967 Hispanic, 718 African American and 825 Asian). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Race/ethnicity-specific distributions of demographics, tumor characteristics, patterns of initial treatment, and survival. RESULTS: African American and Hispanic patients were diagnosed at a younger age than Whites and Asians (P = .001). Hispanics were more likely to be diagnosed with larger tumor size than Whites and Asians (P < .0001). Asians were more likely to be diagnosed with advanced stage and higher tumor grade. Cox-regression revealed that Whites and Asians were significantly less likely to die after UTUC diagnosis than African Americans (HR = .78, 95% Cl = .67-.91 and HR = .75, 95% CI = .61-.91, respectively; all P = < .01). CONCLUSIONS: Our study found that Asians had worse tumor characteristics at the initial presentation than the other groups in this study, but that their risk of dying was lower. Further research is needed to include a larger number of Asian patients to examine subgroup differences and to confirm the paradoxical finding of higher survival with poor clinical characteristics.

Association between Nuclear Morphometry Parameters and Gleason Grade in Patients with Prostatic Cancer.

Objective: Gleason scoring system remains the pathological method of choice for prostate cancer (Pca) grading. However, this method of tumor tissue architectural structure grading is still affected by subjective assessment and might succumb to several disadvantages, mainly inter-observer variability. These limitations might be diminished by determining characteristic cellular heterogeneity parameters which might improve Gleason scoring homogeneity. One of the quantitative tools of tumor assessment is the morphometric characterization of tumor cell nuclei. We aimed to test the relationship between various morphometric measures and the Gleason score assigned to different prostate cancer samples. Materials and Methods: We reviewed 60 prostate biopsy samples performed at a tertiary uro-oncology center. Each slide was assigned a Gleason grade according to the International Society of Urological Pathology contemporary grading system by a single experienced uro-pathologist. Samples were assigned into groups from grades 3 to 5. Next, the samples were digitally scanned (×400 magnification) and sampled on a computer using Image-Pro-Plus software©. Manual segmentation of approximately 100 selected tumor cells per sample was performed, and a computerized measurement of 54 predetermined morphometric properties of each cell nuclei was recorded. These characteristics were used to compare the pathological group grades assigned to each specimen. Results: Initially, of the 54 morphometric parameters evaluated, 38 were predictive of Gleason grade (p < 0.05). On multivariate analysis, 7 independent parameters were found to be discriminative of different Pca grades: minimum radius shape, intensity­minimal gray level, intensity­maximal gray level, character­gray level (green), character­gray level (blue), chromatin color, fractal dimension, and chromatin texture. A formula to predict the presence of Gleason grade 3 vs. grades 4 or 5 was developed (97.2% sensitivity, 100% specificity). Discussion: The suggested morphometry method based on seven selected parameters is highly sensitive and specific in predicting Gleason score ≥ 4. Since discriminating Gleason score 3 from ≥4 is essential for proper treatment selection, this method might be beneficial in addition to standard pathological tissue analysis in reducing variability among pathologists.

Can Endoscopic Appearance, Selective Cytology, and Pathological Sampling During Ureteroscopy Accurately Predict Tumor Grade of Upper-Tract Urothelial Carcinoma?

OBJECTIVE: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU). METHODS: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report. RESULTS: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the "solid"-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease. CONCLUSIONS: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.

Prognostic risk stratification of pathological stage T3N0 bladder cancer after radical cystectomy.

PURPOSE: Patients with pathological T3N0 stage urothelial carcinoma of the bladder show a range of outcomes after radical cystectomy. Given that nomograms have included heterogeneous groups of patients, we focused on and stratified patients with pT3N0 urothelial carcinoma of the bladder after radical cystectomy into prognostically different risk groups to facilitate the development of adjuvant therapy trials for those at high risk. MATERIALS AND METHODS: The study comprised a total of 578 patients from 9 centers worldwide with pT3N0 urothelial carcinoma of the bladder who underwent radical cystectomy without perioperative chemotherapy. We evaluated the effect of pT3 substage at radical cystectomy, age, grade, lymphovascular invasion, margin status and number of lymph nodes removed on recurrence-free survival using Cox regression analysis. A weighted prognostic model was devised. RESULTS: Median followup was 39.4 months (IQR 64). On multivariate analysis pT3 substage at radical cystectomy (pT3b vs pT3a HR 2.056, p <0.0001), lymphovascular invasion (positive vs negative HR 2.004, p <0.0001) and margin status (positive vs negative HR 2.503, p = 0.002) were associated with recurrence-free survival (concordance index 0.66) in the context of generally adequate lymph node dissection, that is with a median of 17 removed. Three risk groups were devised based on weighted variables with a 5-year recurrence-free survival rate of 79% (95% CI 70-84), 57% (95% CI 50-64) and 37% (95% CI 26-48) in the low, intermediate and high risk groups, respectively. CONCLUSIONS: We constructed a user friendly prognostic risk model for patients with pT3N0 urothelial carcinoma of the bladder treated with radical cystectomy based on pT3 substage at radical cystectomy, lymphovascular invasion and margin status. These data warrant validation and may enable tailored monitoring and selection of appropriate patients for adjuvant therapy trials.

Prognostic risk stratification of pathological stage T2N0 bladder cancer after radical cystectomy.

OBJECTIVE: • To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high-risk patients. PATIENTS AND METHODS: • The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. • The effect of residual pT-stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence-free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables. RESULTS: • The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with

Urologists' attitudes regarding information sharing with prostate cancer patients--is there a common ground for collaboration with family physicians?

Clinicians often fail to adequately meet prostate cancer patients' information needs, and patients may receive different kinds of information from their doctors. This study aims to describe urologists' attitudes regarding information sharing with prostate cancer patients and to compare these findings with the previously published attitudes of Israeli family physicians. A questionnaire (11 items) was mailed to 87 board-certified practicing urologists. Fifty-four physicians (66%) completed the questionnaires. Sixty-one percent of respondents stated that patients should be told the complete truth about their disease. Ninety-six percent of respondents felt competent at breaking bad news and stated they would discuss emotions with patients. The majority of physicians would provide general information when referring for a medical procedure, discussing treatment options or a patient's prognosis. Fifty-seven percent of respondents preferred that patients be autonomous in their decision making. Only 26% of respondents believed that family physicians should communicate medical information to patients at the preliminary diagnostic stages. There was no significant difference in the attitudes expressed by urologists and family physicians towards the amount of information they would share with prostate cancer patients and in their preferences regarding treatment decision making. Urologists in Israel recognize the importance of sharing information with prostate cancer patients. Although urologists share similar attitudes with family physicians, they do not recognize the role that family physicians play in caring for prostate cancer patients. Further studies are needed to design and implement effective ways to improve the communication and collaboration between urologists and family physicians for the benefit of prostate cancer patients.

A comparison between 68Ga-labeled prostate-specific membrane antigen-PET/CT and multiparametric MRI for excluding regional metastases prior to radical prostatectomy.

OBJECTIVES: To compare the ability of 68Ga -PSMA PET/CT (PSMA PET/CT) and multiparametric MRI (mpMRI) to exclude lymph node invasion (LNI) in patients who undergo radical prostatectomy (RP). MATERIALS AND METHODS: A multicenter cohort of patients who underwent PSMA PET/CT and pelvic mpMRI prior to RP with pelvic lymph node dissection (PLND) was analyzed. Increased Ga68-PSMA uptake on PET/CT and enlarged (> 10 mm) or abnormal lymph nodes on mpMRI were considered positive findings. The final surgical pathology served as the standard of reference. The negative predictive value (NPV) was calculated for each modality separately, as well as the combined value. RESULTS: Included were 89 patients with D'Amico intermediate (45%) or high-risk (55%) prostate cancer. The median number of extracted LN was 9 (IQR 6-14). LNI was found in 12 (13.5%) patients. The NPV of mpMRI, PSMA PET/CT, and the two tests combined were 87%, 89%, and 90%, in the entire cohort, 95%, 97%, and 97% in patients with intermediate-risk disease, and 80%, 82%, and 83% in patients with high-risk disease, respectively. The median diameter of LN missed by both imaging and the median intranodal tumor diameter was 5.5 (IQR 3-10) mm and 1 (IQR 1-3) mm, respectively. CONCLUSIONS: PSMA PET/CT and mpMRI demonstrated similar performance in excluding pelvic LNI with NPV of approximately 90%. The combination of both tests does not improve NPV significantly. Therefore, even in the era of advanced imaging, PLND is still recommended for accurate staging, especially in the high-risk population.

Residual pathological stage at radical cystectomy significantly impacts outcomes for initial T2N0 bladder cancer.

PURPOSE: We hypothesized that in patients with T2N0 stage disease at transurethral bladder tumor resection a lower residual cancer stage (P1N0 or less) at radical cystectomy may correlate with improved outcomes relative to those with residual P2N0 disease. MATERIALS AND METHODS: We analyzed 208 patients with T2N0 stage disease at transurethral bladder tumor resection whose tumors were organ confined at radical cystectomy (P2 or lower, pN0). None received perioperative chemotherapy. Kaplan-Meier as well as univariable and multivariable Cox regression models addressed the effect of residual pT stage at radical cystectomy on recurrence and cancer specific mortality rates. Covariates consisted of age, gender, grade, lymphovascular invasion, carcinoma in situ, number of lymph nodes removed and year of surgery. RESULTS: Residual pT stage at radical cystectomy was P0 in 24 (11.5%) patients, Pa in 9 (4.3%), PCIS in 22 (10.6%), P1 in 35 (16.8%) and P2 in 118 (56.7%). Median followup of censored patients was 55.7 months for recurrence and 52.1 months for cancer specific mortality analyses. The 5-year recurrence-free survival rates of patients with P0/Pa/PCIS, P1 and P2 stage disease were 100%, 85% and 75%, respectively. The 5-year cancer specific survival rates for the same cohorts were 100%, 93% and 81%, respectively. On multivariable analysis the effect of residual stage P1 or lower at radical cystectomy achieved independent predictor status for recurrence (adjusted HR 0.20, p = 0.002) and cancer specific mortality (adjusted HR 0.24, p = 0.02). CONCLUSIONS: Down staging from initial T2N0 bladder cancer at transurethral bladder tumor resection to lower stage at radical cystectomy significantly reduces recurrence and cancer specific mortality. Further validation of this finding is warranted.

Macroscopic, but not microscopic, perivesical fat invasion at radical cystectomy is an adverse predictor of recurrence and survival.

OBJECTIVE: To examine whether the presence of microscopic (pT3a) or macroscopic (pT3b) disease worsens the prognosis relative to pT2 disease at radical cystectomy, as the prognostic significance of pT3a vs pT3b perivesical fat invasion (pT3) is controversial. PATIENTS AND METHODS: In all, 242 patients with pT3 disease (pT3a in 88, pT3b in 121) had radical cystectomy and bilateral pelvic lymphadenectomy for transitional cell carcinoma of the urinary bladder; they were compared with 172 who had organ-confined muscle-invasive disease (pT2). For the analyses we used univariable and multivariable Cox regression models of recurrence and cancer-specific survival, adjusted for age, tumour grade, lymphovascular invasion and the presence of lymph node metastases. RESULTS: In multivariable analyses, microscopic perivesical fat extension (pT3a) was not associated with higher recurrence (P = 0.3) or the mortality rate (P = 0.06) vs pT2 disease. Conversely, the presence of deep perivesical fat extension (pT3b) was associated with 1.8 times the rate of recurrence (P = 0.002) and with twice the rate of death (P = 0.001) vs pT2 disease. CONCLUSION: These findings imply that a detailed assessment of the cystectomy specimen for the presence of microscopic perivesical fat invasion might not be necessary, as the presence of pT3a disease has no strong effect on recurrence or mortality. Moreover, patients with pT3a disease might not require more aggressive therapy than their counterparts with pT2 disease. However, further validation of our data is required.

Adjuvant chemotherapy for bladder cancer does not alter cancer-specific survival after cystectomy in a matched case-control study.

OBJECTIVE: To assess the effect of adjuvant chemotherapy (ACHT; methotrexate, vinblastine, adriamycin and cisplatin, MVAC, or gemcitabine/cisplatin, GC) on the rate of cancer-specific survival and overall survival, as the benefit of ACHT after radical cystectomy (RC) for bladder cancer is controversial. PATIENTS AND METHODS: Within a study group of 958 patients treated with RC between 1984 and 2003, we identified 274 (29.0%) with a high risk of progression due to pT3 or pT4 and/or pN1-3 stages. Of these, 129 (46.6%) received ACHT (MVAC in 103, GC in 26). These patients were then matched with the remaining patients who were unexposed to ACHT. Exact matches were made for pT stage, tumour grade, pN stage and lymphovascular invasion. Age (+/-5 years) and year of surgery (+/-5 years) were calliper-matched. Matching resulted in 62 patients treated with RC/ACHT and 65 treated with RC alone. Kaplan-Meier, life-table and Cox regression analyses were used to assess cancer-specific and overall survival. RESULTS: There was no statistically significant difference in cancer-specific survival probabilities at 5 years after RC between the two groups (relative risk 1.2; P = 0.5). There was also no difference in overall survival at 5 years (1.1; P = 0.7). In multivariable analyses the delivery of adjuvant chemotherapy was not an independent predictor for survival endpoints (P = 0.3 for cancer-specific and 0.3 for overall survival). CONCLUSIONS: This matched case-control analysis showed that either MVAC or GC chemotherapy had no effect on cancer-specific or overall survival after RC in high-risk patients. Further randomized long-term studies are necessary to confirm these results.

Nomograms provide improved accuracy for predicting survival after radical cystectomy.

AIMS: To develop multivariate nomograms that determine the probabilities of all-cause and bladder cancer-specific survival after radical cystectomy and to compare their predictive accuracy to that of American Joint Committee on Cancer (AJCC) staging. METHODS: We used Cox proportional hazards regression analyses to model variables of 731 consecutive patients treated with radical cystectomy and bilateral pelvic lymphadenectomy for bladder transitional cell carcinoma. Variables included age of patient, gender, pathologic stage (pT), pathologic grade, carcinoma in situ, lymphovascular invasion (LVI), lymph node status (pN), neoadjuvant chemotherapy (NACH), adjuvant chemotherapy (ACH), and adjuvant external beam radiotherapy (AXRT). Two hundred bootstrap resamples were used to reduce overfit bias and for internal validation. RESULTS: During a mean follow-up of 36.4 months, 290 of 731 (39.7%) patients died; 196 of 290 patients (67.6%) died of bladder cancer. Actuarial all-cause survival estimates were 56.3% [95% confidence interval (95% CI), 51.8-60.6%] and 42.9% (95% CI, 37.3-48.4%) at 5 and 8 years after cystectomy, respectively. Actuarial cancer-specific survival estimates were 67.3% (62.9-71.3%) and 58.7% (52.7-64.2%) at 5 and 8 years, respectively. The accuracy of a nomogram for prediction of all-cause survival (0.732) that included patient age, pT, pN, LVI, NACH, ACH, and AXRT was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.615). Similarly, the accuracy of a nomogram for prediction of cancer-specific survival that included pT, pN, LVI, NACH, and AXRT (0.791) was significantly superior (P=0.001) to that of AJCC staging-based risk grouping (0.663). CONCLUSIONS: Multivariate nomograms provide a more accurate and relevant individualized prediction of survival after cystectomy compared with conventional prediction models, thereby allowing for improved patient counseling and treatment selection.