Giovanni Grimaldi

An increased body mass index is associated with a worse prognosis in patients administered BCG immunotherapy for T1 bladder cancer

PurposeThe body mass index (BMI) may be associated with an increased incidence and aggressiveness of urological cancers. In this study, we aimed to evaluate the impact of the BMI on survival in patients with T1G3 non-muscle-invasive bladder cancer (NMIBC).MethodsA total of 1155 T1G3 NMIBC patients from 13 academic institutions were retrospectively reviewed and patients administered adjuvant intravesical Bacillus Calmette–Guérin (BCG) immunotherapy with maintenance were included. Multivariable Cox regression analysis was performed to identify factors predictive of recurrence and progression.ResultsAfter re-TURBT, 288 patients (27.53%) showed residual high-grade NMIBC, while 867 (82.89%) were negative. During follow-up, 678 (64.82%) suffered recurrence, and 303 (30%) progression, 150 (14.34%) died of all causes, and 77 (7.36%) died of bladder cancer. At multivariate analysis, tumor size (hazard ratio [HR]:1.3; p = 0.001), and multifocality (HR:1.24; p = 0.004) were significantly associated with recurrence (c-index for the model:55.98). Overweight (HR: 4; p < 0.001) and obesity (HR:5.33 p < 0.001) were significantly associated with an increased risk of recurrence. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 9.9. For progression, we found that tumor size (HR:1.63; p < 0.001), multifocality (HR:1.31; p = 0.01) and concomitant CIS (HR: 2.07; p < 0.001) were significant prognostic factors at multivariate analysis (C-index 63.8). Overweight (HR: 2.52; p < 0.001) and obesity (HR: 2.521 p < 0.001) were significantly associated with an increased risk of progression. Addition of the BMI to a model that included standard clinicopathological factors increased the C-index by 1.9.ConclusionsThe BMI could have a relevant role in the clinical management of T1G3 NMIBC, if associated with bladder cancer recurrence and progression. In particular, this anthropometric factor should be taken into account at initial diagnosis and in therapeutic strategy decision making.

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.

Exploring the molecular aspects associated with testicular germ cell tumors: a review

Testicular germ cell tumors (TGCTs) represent the most common solid tumors affecting young men. They constitute a distinct entity because of their embryonic origin and their unique biological behavior. Recent preclinical data regarding biological signaling machinery as well as genetic and epigenetic mechanisms associated with molecular patterns of tumors have contribute to explain the pathogenesis and the differentiation of TGCTs and to understand the mechanisms responsible for the development of resistance to treatment. In this review, we discuss the main genetic and epigenetic events associated with TGCTs development in order to better define their role in the pathogenesis of these tumors and in cisplatin-acquired resistance.

Predictors of Residual T1 High Grade on Re-Transurethral Resection in a Large Multi-Institutional Cohort of Patients with Primary T1 High-Grade/Grade 3 Bladder Cancer

The aim of this multi-institutional study was to identify predictors of residual high-grade (HG) disease at re-transurethral resection (reTUR) in a large cohort of primary T1 HG/Grade 3 (G3) bladder cancer patients. A total of 1155 patients with primary T1 HG/G3 bladder cancer from 13 academic institutions that underwent a reTUR within 6 weeks after first TUR were evaluated. Logistic regression analysis was performed to assess the association of predictive factors with residual HG at reTUR. Residual HG cancer was found in 288 (24.9%) of patients at reTUR. Patients presenting residual HG cancer were more likely to have carcinoma in situ (CIS) at first resection (p<0.001), multiple tumors (p=0.02), and tumor size larger than 3 cm (p=0.02). Residual HG disease at reTUR was associated with increased preoperative neutrophil-to-lymphocytes ratio (NLR) (p=0.006) and body mass index (BMI)>=25 kg/m2. On multivariable analysis, independent predictors for HG residual disease at reTUR were tumor size >3cm (OR = 1.37; 95% CI: 1.02-1.84, p=0.03), concomitant CIS (OR 1.92; 95% CI: 1.32-2.78, p=0.001), being overweight (OR= 2.08; 95% CI: 1.44-3.01, p<0.001) and obesity (OR 2.48; 95% CI: 1.64-3.77, p<0.001). A reTUR in high grade T1 bladder cancer is mandatory as about 25% of patients, presents residual high grade disease. Independent predictors to identify patients at risk of residual high grade disease after a complete TUR include tumor size, presence of carcinoma in situ, and BMI >=25 kg/m2.

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.

How to Perform a Good TURBT

Transurethral bladder resection of Bladder Tumor (TURBT) is a crucial procedure in the management of Bladder Cancer. It has the double purpose of establishing the pathologic diagnosis, local staging and starting the treatment in the setting of non-muscle invasive tumors. A complete removal of all macroscopic visible lesions and biopsies of suspicious areas is essential for the correct management of the patient.