A risk-group classification model in patients with bladder cancer under neoadjuvant cisplatin-based combination chemotherapy.

The objective of the current research was to explore the potential prognostic value of readily available clinical and pathologic variables in bladder cancer. The novel association found between cholesterol levels and prognosis may provide the rationale for exploring novel treatments. Patients included had histologically confirmed urothelial bladder cancer and were treated with at least 3 cycles of cisplatin-based neoadjuvant chemotherapy before radical cystectomy with lymphadenectomy. A total of 245 patients at low, intermediate and high risk, presenting with 0-1, 2 or 3-4 risk factors, including positive lymph nodes, Hb <12.8, NLR ≥2.7 and cholesterol levels ≥199, were included. Five-year cancer-specific survival rate was 0.67, 0.78 and 0.94 at high, intermediate and low risk, respectively. Total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and may be incorporated in a clinically meaningful risk-group classification model.

Lay abstract This present study assessed a large group of patients with urothelial bladder cancer treated with chemotherapy followed by radical cystectomy, to capture the predictive power of commonly collected clinical, pathological and biochemical factors. The design of the study highlighted that higher cholesterol levels at the time of cystectomy were associated with shorter cancer-specific survival. This finding suggests that high blood-cholesterol levels truly have a negative influence on surviving cancer. In conclusion, total cholesterol levels at the time of cystectomy may represent a commonly assessable prognostic factor and could be incorporated into a clinically meaningful and valuable risk-group classification model.

High-Grade T1 on Re-Transurethral Resection after Initial High-Grade T1 Confers Worse Oncological Outcomes: Results of a Multi-Institutional Study.

INTRODUCTION: The aim of this multicenter study was to investigate the prognostic impact of residual T1 high-grade (HG)/G3 tumors at re-transurethral resection (TUR of bladder tumor) in a large multi-institutional cohort of patients with primary T1 HG/G3 bladder cancer (BC). PATIENTS AND METHODS: The study period was from January 2002 to -December 2012. A total of 1,046 patients with primary T1 HG/G3 and who had non-muscle invasive BC (NMIBC) on re-TUR followed by adjuvant intravesical Bacillus Calmette-Guerin (BCG) therapy with maintenance were included. Endpoints were time to disease recurrence, progression, and overall and cancer-specific death. RESULTS: A total of 257 (24.6%) patients had residual T1 HG/G3 tumors. The presence of concomitant carcinoma in situ, multiple and large tumors (> 3 cm) at first TUR were associated with residual T1 HG/G3. Five-year recurrence-free survival (RFS), progression-free survival (PFS), overall survival (OS), and cancer-specific survival (CSS) were 17% (CI 11.8-23); 58.2% (CI 50.7-65); 73.7% (CI 66.3-79.7); and 84.5% (CI 77.8-89.3), respectively, in patients with residual T1 HG/G3, compared to 36.7% (CI 32.8-40.6); 71.4% (CI 67.3-75.2); 89.8% (CI 86.6-92.3); and 95.7% (CI 93.4-97.3), respectively, in patients with NMIBC other than T1 HG/G3 or T0 tumors. Residual T1 HG/G3 was independently associated with RFS, PFS, OS, and CSS in multivariable analyses. CONCLUSIONS: Residual T1 HG/G3 tumor at re-TUR confers worse prognosis in patients with primary T1 HG/G3 treated with maintenance BCG. Patients with residual T1 HG/G3 for primary T1 HG/G3 are very likely to fail BCG therapy alone.

Modified Glasgow Prognostic Score as a Predictor of Recurrence in Patients with High Grade Non-Muscle Invasive Bladder Cancer Undergoing Intravesical Bacillus Calmette-Guerin Immunotherapy.

BACKGROUND: A systemic inflammatory marker, the modified Glasgow prognostic score (mGPS), could predict outcomes in non-muscle-invasive bladder cancer (NIMBC). We aimed to investigate the predictive power of mGPS in oncological outcomes in HG/G3 T1 NMIBC patients undergoing Bacillus Calmette-Guérin (BCG) therapy. METHODS: We retrospectively reviewed patient's medical data from multicenter institutions. A total of 1382 patients with HG/G3 T1 NMIBC have been administered adjuvant intravesical BCG therapy, every week for 3 weeks given at 3, 6, 12, 18, 24, 30 and 36 months. The analysis of mGPS for recurrence and progression was performed using multivariable and univariable Cox regression models. RESULTS: During follow-up, 659 patients (47.68%) suffered recurrence, 441 (31.91%) suffered progression, 156 (11.28%) died of all causes, and 67 (4.84%) died of bladder cancer. At multivariable analysis, neutrophil to lymphocyte ratio [hazard ratio (HR): 7.471; p = 0.0001] and erythrocyte sedimentation rate (ESR) (HR: 0.706; p = 0.006 were significantly associated with recurrence. mGPS has no statistical significance for progression (p = 0.076). Kaplan-Meier survival analysis showed a significant difference in survival among patients from different mGPS subgroups. Five-year OS was 93% (CI 95% 92-94), in patients with mGPS 0, 82.2% (CI 95% 78.9-85.5) in patients with mGPS 1 and 78.1% (CI 95% 60.4-70) in mGPS 2 patients. Five-year CSS was 98% (CI 95% 97-99) in patients with mGPS 0, 90% (CI 95% 87-94) in patients with mGPS 1, and 100% in mGPS 2 patients. Limitations are applicable to a retrospective study. CONCLUSIONS: mGPS may have the potential to predict recurrence in HG/G3 T1 NMIBC patients, but more prospective, with large cohorts, studies are needed to study the influence of systemic inflammatory markers in prediction of outcomes in NMIBC for a definitive conclusion.

Systemic combining inflammatory score (SCIS): a new score for prediction of oncologic outcomes in patients with high-risk non-muscle-invasive urothelial bladder cancer.

BACKGROUND: An accurate and early diagnosis of bladder cancer (BC) is essential to offer patients the most appropriate treatment and the highest cure rate. For this reason, patients need to be best stratified by class and risk factors. We aimed to develop a score able to better predict cancer outcomes, using serum variables of inflammation. METHODS: A total of 1,510 high-risk non-muscle invasive bladder cancer (NMIBC) patients were included in this retrospective observational study. Patients with pathologically proven T1 HG/G3 at first TURBT were included. Systemic combined inflammatory score (SCIS) was calculated according to systemic inflammatory markers (SIM), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) dichotomized (final score from 0 to 3). RESULTS: After 48 months of follow-up (IQR 40.0-73.0), 727 patients recurred (48.1%), 485 progressed (32.1%), 81 died for cancer (7.0%), and 163 died for overall causes (10.8%). Overall, 231 (15.3%) patients had concomitant Cis, 669 (44.3%) patients had multifocal pathology, 967 (64.1%) patients had tumor size >3 cm. Overall, 357 (23.6%) patients received immediate-intravesical therapy, 1,356 (89.8%) received adjuvant intravesical therapy, of which 1,382 (91.5%) received BCG, 266 (17.6%) patients received mitomycin C, 4 (0.5%) patients received others intravesical therapy. Higher SCIS was independently predictive of recurrence (hazard ratio HR 1.5, 1.3 and 2.2) and cancer specific mortality for SCIS 0 and 3 (HR: 1.61 and 2.3), and overall mortality for SCIS 0 and 3 (HR: 2.4 and 3.2). Conversely, SCIS was not associated with a higher probability of progression. CONCLUSIONS: The inclusion of the SCIS in clinical practice is simple to apply and can help improve the prediction of cancer outcomes. It can identify patients with high-grade BC who are more likely to experience disease mortality.

Neutrophil percentage-to-albumin ratio predicts mortality in bladder cancer patients treated with neoadjuvant chemotherapy followed by radical cystectomy.

AIM: To investigate the prognostic role of neutrophil percentage-to-albumin ratio (NPAR) in muscle-invasive bladder cancer (MIBC) patients treated with neoadjuvant chemotherapy (NAC) and radical cystectomy (RC). PATIENTS & METHODS: 213 patients were included. INCLUSION CRITERIA: Nonmetastatic, MIBC (cT2-T4aN0M0), at least three cycles of NAC, undergone RC and with blood count within 30 days before NAC. RESULTS: Five-years overall survival (OS) with NPAR >18 was 34.06% (95% CI: 18.3-50.5) and 65.37% (95% CI: 52.4-75.6) with NPAR <18. Five years cancer-specific survival (CSS) with NPAR >18 was 42.9% (95% CI: 23.9-60.7) and 74.5% (95% CI: 62.6-83.1) with NPAR <18 (p < 0.001). In multivariable analysis, NPAR increased OS of 1.3 points and CSS of 4.37 points. CONCLUSION: High NPAR prior to NAC seems to be a strong predictor of OS and CSS in MIBC patients treated with NAC and RC.

Type 2 diabetes mellitus predicts worse outcomes in patients with high-grade T1 bladder cancer receiving bacillus Calmette-Guérin after transurethral resection of the bladder tumor.

OBJECTIVES: The aim of this multicenter study was to investigate the prognostic role of type 2 diabetes mellitus (T2DM) comorbidity in a large multi-institutional cohort of patients with primary T1HG/G3 non-muscle-invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB). MATERIALS AND METHODS: A total of 1,172 patients with primary T1 HG/G3 who had NMIBC on re-TURB and who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance were included. Endpoints were recurrence-free survival and progression-free survival. RESULTS: A total of 231 (19.7%) of patients had T2DM prior to TURB. Five-year recurrence-free survival estimates were 12.5% in patients with T2DM compared to 36% in patients without T2DM, P < 0.0001. Five-year PFS estimates were 60.5% in patients with T2DM compared to 70.2% in patients without T2DM, P = 0.003. T2DM was independently associated with disease recurrence (hazard ratio = 1.41; 95% confidence interval = 1.20-1.66, P < 0.001) and progression (hazard ratio = 1.27; 95% confidence interval = 0.99-1.63, P < 0.001), after adjusting for other known predictive factors such as tumor size, multifocality, T1G3 on re-TURB, body mass index, lymphovascular invasion, and neutrophil-to-lymphocytes ratio. CONCLUSIONS: Given the potential implications for management, prospective validation of this finding along with translational studies designed to investigate the underlying biology of such an association are warranted.

Validation of Neutrophil-to-lymphocyte Ratio in a Multi-institutional Cohort of Patients With T1G3 Non-muscle-invasive Bladder Cancer.

INTRODUCTION: The aim of this multicenter study was to investigate the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and to validate the NLR cutoff of 3 in a large multi-institutional cohort of patients with primary T1 HG/G3 non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: The study period was from January 2002 through December 2012. A total of 1046 patients with primary T1 HG/G3 who had NMIBC on re-transurethral bladder resection (TURB) who received adjuvant intravesical bacillus Calmette-Guérin therapy with maintenance from 13 academic institutions were included. Endpoints were time to disease, and recurrence-free (RFS), progression-free (PFS), overall (OS), and cancer-specific survival (CSS). RESULTS: A total of 512 (48.9%) of patients had NLR ≥ 3 prior to TURB. High pretreatment NLR was associated with female gender and residual T1HG/G3 on re-TURB. The 5-year RFS estimates were 9.4% (95% confidence interval [CI], 6.8%-12.4%) in patients with NLR ≥ 3 compared with 58.8% (95% CI, 54%-63.2%) in patients with NLR < 3; the 5-year PFS estimates were 57.1% (95% CI, 51.5%-62.2%) versus 79.2% (95% CI, 74.7%-83%; P < .0001); the 10-year OS estimates were 63.6% (95% CI, 55%-71%) versus 66.5% (95% CI, 56.8%-74.5%; P = .03); the 10-year CSS estimates were 77.4% (95% CI, 68.4%-84.2%) versus 84.3% (95% CI, 76.6%-89.7%; P = .004). NLR was independently associated with disease recurrence (hazard ratio [HR], 3.34; 95% CI, 2.82-3.95; P < .001), progression (HR, 2.18; 95% CI, 1.71-2.78; P < .001) and CSS (HR, 1.65; 95% CI, 1.02-2.66; P = .03). The addition of NLR to a multivariable model that included established features increased its discrimination for predicting of RFS (+6.9%), PFS (+1.8%), and CSS (+1.7%). CONCLUSIONS: Pretreatment NLR ≥ 3 was a strong predictor for RFS, PFS, and CSS in patients with primary T1 HG/G3 NMIBC. It could help in the decision-making regarding intensity of therapy and follow-up.