Metabolic syndrome is associated with advanced prostate cancer in patients treated with radical retropubic prostatectomy. Results from a multicentre prospective study

BACKGROUND: Prostate cancer (PCa) is the most common non-skin cancer in USA and the second leading cause of cancer death in Western Countries. Despite the high mortality associated with PCa, the only established risk factors are age, race and family history. A possible association between metabolic syndrome (MetS) and PCa was firstly described in 2004 and several subsequent studies in biopsy cohorts have shown conflicting results. Aim of our multicentre prospective study was to investigate the association between MetS and PCa in men undergoing radical prostatectomy (RP). METHODS: From January 2012 to June 2015, 349 consecutive men undergoing RP for PCa at three centres in Italy were enrolled into a prospective database. Body Mass Index (BMI) as well as waist circumference was measured before RP. Blood samples were also collected and tested for total PSA, fasting glucose, triglycerides and HDLs. Blood pressure was also recorded. We evaluated the association between MetS, defined according to Adult Treatment Panel III, PCa stage (advanced stage defined as pT ≥ 3 or N1) and grade (high grade defined as Gleason Score ≥ 4 + 3) using logistic regression analyses. RESULTS: Median age and preoperative PSA levels were 66 years (IQR: 61-69) and 7 ng/ml (IQR: 5-10), respectively. Median BMI was 26.12 kg/m(2) (IQR 24-29) with 56 (16 %) obese (BMI ≥ 30 kg/m(2)) patients and 87 (25 %) patients with MetS. At pathological evaluation, advanced PCa and high-grade disease were present in 126 (36 %) and 145 (41.5 %) patients, respectively. MetS was significantly associated with advanced PCa (45/87, 51 % vs 81/262, 31 %; p = 0.008) and high-grade disease (47/87, 54 % vs 98/262, 37 %; p = 0.001). On multivariable analysis, MetS was an independent predictor of pathological stage ≥ pT3a or N1 (OR: 2.227; CI: 1.273-3.893; p = 0.005) and Gleason score ≥ 4 + 3 (OR: 2.007, CI: 1.175-3.428; p = 0.011). CONCLUSIONS: We firstly demonstrated in a European radical retropubic prostatectomy cohort study that MetS is associated with an increased risk of high-grade and advanced prostate cancer. Further studies with long term follow-up should evaluate the impact of Mets on PCa survival

The new Epstein gleason score classification significantly reduces upgrading in prostate cancer patients

Purpose: To evaluate the differences between the old and the new Gleason score classification systems in upgrading and downgrading rates. Materials and methods: Between 2012 and 2015, we identified 9703 patients treated with retropubic radical prostatectomy (RP) in four tertiary centers. Biopsy specimens as well as radical prostatectomy specimens were graded according to both 2005 Gleason and 2014 ISUP five-tier Gleason grading system (five-tier GG system). Upgrading and downgrading rates on radical prostatectomy were first recorded for both classifications and then compared. The accuracy of the biopsy for each histological classification was determined by using the kappa coefficient of agreement and by assessing sensitivity, specificity, positive and negative predictive value. Results: The five-tier GG system presented a lower clinically significant upgrading rate (1895/9703: 19,5% vs 2332/9703:24.0%; p =.001) and a similar clinically significant downgrading rate (756/9703: 7,7% vs 779/9703: 8%; p =.267) when compared to the 2005 ISUP classification. When evaluating their accuracy, the new five-tier GG system presented a better specificity (91% vs 83%) and a better negative predictive value (78% vs 60%). The kappa-statistics measures of agreement between needle biopsy and radical prostatectomy specimens were poor and good respectively for the five-tier GG system and for the 2005 Gleason score (k = 0.360 ± 0.007 vs k = 0.426 ± 0.007). Conclusions: The new Epstein classification significantly reduces upgrading events. The implementation of this new classification could better define prostate cancer aggressiveness with important clinical implications, particularly in prostate cancer management

Serum levels of chromogranin are not predictive of poorly differentiated prostate cancer: Results from a multicenter radical prostatectomy cohort

Recently a possible link between elevated Chromogranin A (CgA) levels and poorly differentiated prostate cancer has been proposed. The aim of our study was to explore the association of CgA levels and the risk of poorly differentiated prostate cancer (PCa) in men undergoing radical retropubic prostatectomy (RRP)

Development and external validation of nomograms predicting disease-free and cancer-specific survival after radical cystectomy

Purpose: To develop two nomograms predicting disease-free survival (DFS) and cancer-specific survival (CSS) and to externally validate them in multiple series. Methods: Prospectively collected data from a single-centre series of 818 consecutive patients who underwent RC and PLND were used to build the nomogram. External validation was performed in 3,173 patients from 7 centres worldwide. Time to recurrence and to cancer-specific death were addressed with univariable and multivariable analyses. Nomograms were built to predict 2-, 5- and 8-year DFS and CSS probabilities. Predictive accuracy was quantified using the concordance index. Results: Age, pathologic T stage, lymph-node density and extent of PLND were independent predictors of DFS and CSS (p < 0.05). Discrimination accuracies for DFS and CSS at 2, 5 and 8 years were 0.81, 0.8, 0.79 and 0.82, 0.81, 0.8, respectively, with a slight overestimation at calibration plots beyond 24 months. In the external series, predictive accuracies for DFS and CSS at 2, 5 and 8 years were 0.83, 0.82, 0.82 and 0.85, 0.85, 0.83 for European centres; 0.73, 0.72, 0.71 and 0.80, 0.74, 0.68 for African series; 0.76, 0.74, 0.71 and 0.79, 0.76, 0.73 for American series. Conclusions: These nomograms developed from a contemporary series are simple clinical tools and provide optimal oncologic outcome prediction in all external cohorts

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

BACKGROUND: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. METHODS: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). RESULTS: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. CONCLUSIONS: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care