Danilo Bottero

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy.

OBJECTIVE To compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa). METHODS AND MATERIALS We evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro-prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume > 0.5 ml, pathologic Gleason sum ≥ 7, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions. RESULTS On multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume > 0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase. Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all Ps < 0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P < 0.05 with a gain of 3.6%). In the subset of patients with GS ≤ 6, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS ≥ 7. For these outcomes, PCA3 did not add incremental predictive value. CONCLUSIONS In a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa.

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

Purpose The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy. Methods A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score. Results Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI. Conclusions mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.

Salvage Radical Prostatectomy after External Beam Radiation Therapy: A Systematic Review of Current Approaches

Background: Radical external beam radiotherapy (EBRT) is a standard treatment for prostate cancer patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. For these patients, local salvage therapy such as radical prostatectomy, cryotherapy, and brachytherapy may be indicated. Objective: The objectives of this review were to analyze the eligibility criteria for careful selection of appropriate patients and to evaluate the oncological results and complications for each method. Methods: A review of the literature was performed to identify studies of local salvage therapy for patients who had failed primary EBRT for localized prostate cancer. Results: Most studies demonstrated that local salvage therapy after EBRT may provide long-term local control in appropriately selected patients, although toxicity is often significant. Conclusions: Our results suggest that for localized prostate cancer recurrence after EBRT, the selection of a local treatment modality should be made on a patient-by-patient basis. An improvement in selection criteria and an integrated definition of biochemical failure for all salvage methods are required to determine which provides the best oncological outcome and least comorbidity.

Body mass index was associated with upstaging and upgrading in patients with low-risk prostate cancer who met the inclusion criteria for active surveillance

BACKGROUND Obesity is associated with an increased risk of high-grade prostate cancer (PCa). The effect of body mass index (BMI) as a predictor of progression in men with low-risk PCa has been only poorly assessed. In this study, we evaluated the association of BMI with progression in patients with low-risk PCa who met the inclusion criteria for the active surveillance (AS) protocol. METHODS We assessed 311 patients who underwent radical prostatectomy and were eligible for AS according to the following criteria: clinical stage T2a or less, prostate-specific antigen level < 10 ng/ml, 2 or fewer cores involved with cancer, Gleason score ≤ 6 grade, and prostate-specific antigen density < 0.2 ng/ml/cc. Reclassification was defined as upstaged (pathological stage > pT2) and upgraded (Gleason score ≥ 7; primary Gleason pattern 4) disease. Seminal vesicle invasion, positive lymph nodes, and tumor volume ≥ 0.5 ml were also recorded. RESULTS We found that high BMI was significantly associated with upgrading, upstaging, and seminal vesicle invasion, whereas it was not associated with positive lymph nodes or large tumor volume. At multivariate analysis, 1 unit increase of BMI significantly increased the risk of upgrading, upstaging, seminal vesicle invasion, and any outcome by 21%, 23%, 27%, and 20%, respectively. The differences between areas under the receiver operating characteristics curves comparing models with and without BMI were statistically significant for upgrading (P = 0.0002), upstaging (P = 0.0007), and any outcome (P = 0.0001). CONCLUSIONS BMI should be a selection criterion for inclusion of patients with low-risk PCa in AS programs. Our results support the idea that obesity is associated with worse prognosis and suggest that a close AS program is an appropriate treatment option for obese subjects.

Modified Glasgow Prognostic Score is Associated With Risk of Recurrence in Bladder Cancer Patients After Radical Cystectomy: A Multicenter Experience

Abstract Recently, many studies explored the role of inflammation parameters in the prognosis of urinary cancers, but the results were not consistent. The modified Glasgow Prognostic Score (mGPS), a systemic inflammation marker, is a prognostic marker in various types of cancers. The aim of the present study was to investigate the usefulness of the preoperative mGPS as predictor of recurrence-free (RFS), overall (OS), and cancer-specific (CSS) survivals in a large cohort of urothelial bladder cancer (UBC) patients. A total of 1037 patients with UBC were included in this study with a median follow-up of 22 months (range 3–60 months). An mGPS = 0 was observed in 646 patients (62.3%), mGPS = 1 in 297 patients (28.6 %), and mGPS = 2 in 94 patients (9.1%). In our study cohort, subjects with an mGPS equal to 2 had a significantly shorter median RFS compared with subjects with mGPS equal to 1 (16 vs 19 months, hazard ratio [HR] 1.54, 95% CI 1.31–1.81, P < 0.001) or with subjects with mGPS equal to 0 (16 vs 29 months, HR 2.38, 95% CI 1.86–3.05, P < 0.001). The association between mGPS and RFS was confirmed by weighted multivariate Cox model. Although in univariate analysis higher mGPS was associated with lower OS and CSS, this association disappeared in multivariate analysis where only the presence of lymph node-positive bladder cancer and T4 stage were predictors of worse prognosis for OS and CSS. In conclusion, the mGPS is an easily measured and inexpensive prognostic marker that was significantly associated with RFS in UBC patients.

The emerging role of obesity, diet and lipid metabolism in prostate cancer

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Multiparametric magnetic resonance imaging and frozen-section analysis efficiently predict upgrading, upstaging, and extraprostatic extension in patients undergoing nerve-sparing robotic-assisted radical prostatectomy.

AbstractTo evaluate the role of multiparametric magnetic resonance imaging (mpMRI) in predicting upgrading, upstaging, and extraprostatic extension in patients with low-risk prostate cancer (PCa). MpMRI may reduce positive surgical margins (PSM) and improve nerve-sparing during robotic-assisted radical prostatectomy (RARP) for localized prostate cancer PCa.This was a retrospective, monocentric, observational study. We retrieved the records of patients undergoing RARP from January 2012 to December 2013 at our Institution. Inclusion criteria were: PSA <10 ng/mL; clinical stage <T3a; biopsy Gleason score <7; prostate mpMRI performed preoperatively at our Institution; intraoperative FSA of the posterolateral aspects of the specimen.All the identified lesions were scored according to the Prostate Imaging Reporting and Data System (PIRADS). We considered the lesion with the highest PIRADS score as index lesion. All the included patients underwent nerve-sparing RARP. During surgery, the specimen was sent for FSA of the posterolateral aspects. The surgeon, according to the localization scheme provided by the mpMRI, inked the region of the posterolateral aspect of the prostate that had to be submitted to FSA.We evaluated association between clinical features and PSM, upgrading, upstaging, and presence of unfavorable disease.Two hundred fifty-four patients who underwent nerve-sparing RARP were included. PSM rate was 29.13% and 15.75% at FSA and final pathology respectively. Interestingly, the use of FSA reduced PSM rate in pT3 disease (25.81%). Higher PIRADS scores demonstrated to be related to high probability of upgrading and upstaging. This significativity remains even when considering PIRADS 2–3 versus 4 versus 5 and PIRADS 2–3 versus 4–5. Also PSM at FSA were associated with higher probability of upgrading and upstaging.PIRADS score and FSA resulted to be strictly related to grading and staging, thus being able to predict upgrading and/or upstaging at final pathology.

Biomarkers in localized prostate cancer

Biomarkers can improve prostate cancer diagnosis and treatment. Accuracy of prostate-specific antigen (PSA) for early diagnosis of prostate cancer is not satisfactory, as it is an organ- but not cancer-specific biomarker, and it can be improved by using models that incorporate PSA along with other test results, such as prostate cancer antigen 3, the molecular forms of PSA (proPSA, benign PSA and intact PSA), as well as kallikreins. Recent reports suggest that new tools may be provided by metabolomic studies as shown by preliminary data on sarcosine. Additional molecular biomarkers have been identified by the use of genomics, proteomics and metabolomics. We review the most relevant biomarkers for early diagnosis and management of localized prostate cancer.

Urotensin II receptor on preoperative biopsy is associated with upstaging and upgrading in prostate cancer

AIM A higher Gleason score was associated with a lower tumor urotensin II receptor (UTII-R) expression in prostate cancer patients. METHODS A retrospective review of formalin-fixed paraffin-embedded tumor tissue derived from those who had prostatectomy and matching biopsy specimens was conducted at six Institutions. UTII-R expression was evaluated on biopsy by immunohistochemistry. RESULTS A total of 58 subjects undergoing radical prostatectomy were included. At multivariate analysis, low UTII-R expression was a significant predictor of Gleason upgrading, with an odds ratio of 10.3 (95% CI: 1.55-68.4), and of pathology upstaging, with an odds ratio of 11.1 (95% CI: 1.23-100.48). CONCLUSIONS UTII-R expression on biopsy was associated with Gleason upgrading and pathology upstaging in prostate cancer patients.

Virtue male sling for post-prostatectomy stress incontinence: A prospective evaluation and mid-term outcomes

To evaluate the efficacy and safety of the Virtue® male sling (Coloplast, Humlebaek, Denmark) in a cohort of patients affected by post‐prostatectomy stress urinary incontinence (SUI).