How radical prostatectomy procedures have changed over the last 10 years in Italy: a comparative analysis based on more than 1500 patients participating in the MIRROR-SIU/LUNA and the Pros-IT CNR study.

PURPOSE: Therapeutic strategies for prostate cancer (PCa) have been evolving dramatically worldwide. The current article reports on the evolution of surgical management strategies for PCa in Italy. METHODS: The data from two independent Italian multicenter projects, the MIRROR-SIU/LUNA (started in 2007, holding data of 890 patients) and the Pros-IT-CNR project (started in 2014, with data of 692 patients), were compared. Differences in patients' characteristics were evaluated. Multivariable logistic regression models were used to identify characteristics associated with robot-assisted (RA) procedure, nerve sparing (NS) approach, and lymph node dissection (LND). RESULTS: The two cohorts did not differ in terms of age and prostate-specific antigen (PSA) levels at biopsy. Patients enrolled in the Pros-IT-CNR project more frequently were submitted to RA (58.8% vs 27.6%, p < 0.001) and NS prostatectomy (58.4% vs. 52.9%, p = 0.04), but received LND less frequently (47.7% vs. 76.7%, p < 0.001), as compared to the MIRROR-SIU/LUNA patients. At multivariate logistic models, Lower Gleason Scores (GS) and PSA levels were significantly associated with RA prostatectomy in both cohorts. As for the MIRROR-SIU/LUNA data, clinical T-stage was a predictor for NS (OR = 0.07 for T3, T4) and LND (OR = 2.41 for T2) procedures. As for Pros-IT CNR data, GS ≥ (4 + 3) and positive cancer cores ≥ 50% were decisive factors both for NS (OR 0.29 and 0.30) and LND (OR 7.53 and 2.31) strategies. CONCLUSIONS: PCa management has changed over the last decade in Italian centers: RA and NS procedures without LND have become the methods of choice to treat newly medium-high risk diagnosed PCa.

Patterns of prescription and adherence to European Association of Urology guidelines on androgen deprivation therapy in prostate cancer: an Italian multicentre cross-sectional analysis from the Choosing Treatment for Prostate Cancer (CHOICE) study.

OBJECTIVE: To evaluate both the patterns of prescription of androgen deprivation therapy (ADT) in patients with prostate cancer (PCa) and the adherence to European Association of Urology (EAU) guidelines for ADT prescription. METHODS: The Choosing Treatment for Prostate Cancer (CHOICE) study was an Italian multicentre cross-sectional study conducted between December 2010 and January 2012. A total of 1 386 patients, treated with ADT for PCa (first prescription or renewal of ADT), were selected. With regard to the EAU guidelines on ADT, the cohort was categorized into discordant ADT (Group A) and concordant ADT (Group B). RESULTS: The final cohort included 1 075 patients with a geographical distribution including North Italy (n = 627, 58.3%), Central Italy (n = 233, 21.7%) and South Italy (n = 215, 20.0%). In the category of patients treated with primary ADT, a total of 125 patients (56.3%) were classified as low risk according to D'Amico classification. With regard to the EAU guidelines, 285 (26.51%) and 790 patients (73.49%) were classified as discordant (Group A) and concordant (Group B), respectively. In Group A, patients were more likely to receive primary ADT (57.5%, 164/285 patients) than radical prostatectomy (RP; 30.9%, 88/285 patients), radiation therapy (RT; 6.7%, 19/285 patients) or RP + RT (17.7%, 14/285 patients; P < 0.01). Multivariate logistic regression analysis, adjusted for clinical and pathological variables, showed that patients from Central Italy (odds ratio [OR] 2.86; P < 0.05) and South Italy (OR 2.65; P < 0.05) were more likely to receive discordant ADT. CONCLUSION: EAU guideline adherence for ADT was low in Italy and was influenced by geographic area. Healthcare providers and urologists should consider these results in order to quantify the inadequate use of ADT and to set policy strategies to overcome this risk.

Sonographic appearances of the postoperative testis.

PURPOSE: To describe the sonographic findings observed in the testis in patients who have undergone testicle-sparing surgery and surgical biopsies. METHODS: We reviewed the color Doppler sonographic findings from 14 patients after testicular interventions: 2 open biopsy procedures for infertility and 12 testicle-sparing surgical procedures (1 for spontaneous intratesticular hemorrhage and 11 for small tumors). Ten patients had benign tumors; one had a malignancy. Three patients were symptomatic; all others were studied as follow-up. RESULTS: Hypoechoic and hypovascular lesions at site of surgery were seen in 10 of the 11 patients after tumorectomy; no changes were observed in one patient. The lesions were either linear or an irregularly triangular shape, located at the surgical site, and interpreted as scars. Retraction of the testicular surface was detected in two cases. In the eight patients who underwent follow-up, lesions disappeared in one case, became smaller in two, and remained stable in five. Of the two patients who underwent biopsy, one developed peritesticular hematoma, and both had late hypoechoic scars in the testis. CONCLUSIONS: Hypoechoic and hypovascular scars are a "normal" postoperative pattern after testicle-sparing surgery. They are either linear or triangular, with rectilinear margins. Such findings need to be correctly interpreted and not misinterpreted as recurrences.

Value of bimodal (18)F-choline-PET/MRI and trimodal (18)F-choline-PET/MRI/TRUS for the assessment of prostate cancer recurrence after radiation therapy and radical prostatectomy.

Between 27% and 53% of all patients who undergo radical prostatectomy (RP) or radiation therapy (RT) as the first-line treatment of prostate cancer (PCa) develop a biochemical recurrence. Imaging plays a pivotal role in restaging by helping to distinguish between local relapse and metastatic disease (i.e., lymph-node and skeletal metastases). At present, the most promising tools for assessing PCa patients with biochemical recurrence are multiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET)/computed tomography (CT) with radio-labeled choline derivatives. The main advantage of mpMRI is its high diagnostic accuracy in detecting local recurrence, while choline-PET/CT is able to identify lymph-node metastases when they are not suspicious on morphological imaging. The most recent advances in the field of fusion imaging have shown that multimodal co-registration, synchronized navigation, and combined interpretation are more valuable than the individual; separate assessment offered by different diagnostic techniques. The objective of the present essay was to describe the value of bimodal choline-PET/mpMRI fusion imaging and trimodal choline-PET/mpMRI/transrectal ultrasound (TRUS) in the assessment of PCa recurrence after RP and RT. Bimodal choline-PET/mpMRI fusion imaging allows morphological, functional, and metabolic information to be combined, thereby overcoming the limitations of each separate imaging modality. In addition, trimodal real-time choline-PET/mpMRI/TRUS fusion imaging may be useful for the planning and real-time guidance of biopsy procedures in order to obtain histological confirmation of the local recurrence.

External validation of nomogram predicting the probability of specimen-confined disease (pT2-3a, R0N0) in patients undergoing radical prostatectomy and pelvic lymph node dissection.

INTRODUCTION: Before radical prostatectomy (RP), a nomogram [Briganti et al., Eur Urol 2012;61:584-592] permits to measure the probability of specimen-confined (SC) disease (pT2-pT3a, node negative with negative margins) in high-risk prostate cancer (PCa). The aim of our study was to perform an external validation of this nomogram. MATERIALS AND METHODS: Between 2007 and 2011, 623 patients with high-risk PCa (prostate-specific antigen (PSA) >20 ng/ml and/or biopsy Gleason score ≥8 and/or clinical stage T3) underwent RP and pelvic lymph node dissection at tertiary referral centers. Multivariable logistic regression models predicting the presence of SC disease were built in; we then used the area under curve of the receiver operating characteristic analysis to quantify accuracy of the nomogram to predict SC disease. The extent of over- or underestimation was evaluated within calibration plots. RESULTS: 29% (181/623) of men had SC disease at RP. Preoperative PSA, biopsy Gleason score and stage differed significantly (all p < 0.001) between men with SC disease and those without. External validation of the nomogram showed an acceptable accuracy (area under curve: 66.3, 95% CI 62.4-70%) and a perfect calibration plot. CONCLUSIONS: The external cohort validates the original nomogram, with perfect calibration characteristics. The adequate although reduced accuracy may reflect the wide spectrum and behavior of the so-called high-risk PCa.

Myxoid liposarcoma of the spermatic cord: US and MR imaging findings.

We report a patient with myxoid liposarcoma of the spermatic cord in whom combined use of both ultrasound (US) and MRI helped to suggest the diagnosis. The lesion was solid at US and vascularized at color Doppler. T1-weighted MRI did not show fat within it; on T2-weighted images it had high signal intensity, with a cyst-like appearance. It is known that fat-poor myxoid liposarcomas with high water content may mimic a cystic lesion on non-contrast-enhanced MR; then, a combination of MRI findings, suggesting a cyst, and of US findings, showing the mass was actually solid and vascularized, allowed preoperatively the diagnosis of fat-poor myxoid liposarcoma.

CD39 is highly involved in mediating the suppression activity of tumor-infiltrating CD8+ T regulatory lymphocytes.

CD39 is an ectoenzyme, present on different immune cell subsets, which mediates immunosuppressive functions catalyzing ATP degradation. It is not known whether CD39 is expressed and implicated in the activity of CD8+ regulatory T lymphocytes (Treg). In this study, CD39 expression and function was analyzed in both CD8+ and CD4+CD25(hi) Treg from the peripheral blood of healthy donors as well as from tumor specimens. CD39 was found expressed by both CD8+ (from the majority of healthy donors and tumor patients) and CD4+CD25(hi) Treg, and CD39 expression correlated with suppression activity mediated by CD8+ Treg. Importantly, CD39 counteraction remarkably inhibited the suppression activity of CD8+ Treg (both from peripheral blood and tumor microenvironment) suggesting that CD39-mediated inhibition constitutes a prevalent hallmark of their function. Collectively, these findings, unveiling a new mechanism of action for CD8+ Treg, provide new knowledge on intratumoral molecular pathways related to tumor immune escape, which could be exploited in the future for designing new biological tools for anticancer immune intervention.

A multi-peptide, dual-adjuvant telomerase vaccine (GX301) is highly immunogenic in patients with prostate and renal cancer.

BACKGROUND: Anti-tumor vaccination is a new frontier in cancer treatment applicable to immunogenic neoplasms such as prostate and renal cancers. GX301 is a vaccine constituted by four telomerase peptides and two adjuvants, Montanide ISA-51 and Imiquimod. OBJECTIVE: The aim of this study was to analyze safety and tolerability of GX301 in an open-label, phase I/II trial. Immunological and clinical responses were also evaluated as secondary endpoints. EXPERIMENTAL DESIGN: GX301 was administered by intradermally injecting 500 µg of each peptide (dissolved in Montanide ISA-51) in the skin of the abdomen. Imiquimod was applied as a cream at the injection sites. The protocol included 8 administrations at days 1, 3, 5, 7, 14, 21, 35, 63. Eligible patients were affected with stage IV prostate or renal cancer resistant to conventional treatments. Patients were clinically and immunologically monitored up to 6 months from the first immunization. RESULTS: No grade 3-4 adverse events were observed. Evidence of vaccine-specific immunological responses was detected in 100 % of patients. Disease stabilization occurred in 4 patients. Prolonged progression-free survival and overall survival were observed in patients showing a full pattern of vaccine-specific immunological responses. CONCLUSION: GX301 demonstrated to be safe and highly immunogenic. Further studies are needed to determine its clinical efficacy.

External validation of the preoperative Karakiewicz nomogram in a large multicentre series of patients with renal cell carcinoma.

PURPOSE: To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC). METHODS: Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration. RESULTS: A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 %, P < 0.001) and non-metastatic (92.2 vs. 88.1 %, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 % (95 % CI, 84.4-91.4) at 1 year, 87.0 % (95 % CI, 84.4-89.5) at 2 years, 84.7 % (95 % CI, 82.3-87.1) at 5 years, and 85.9 % (95 % CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot. CONCLUSION: The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting.

Quality of life in women undergoing urinary diversion for bladder cancer: results of a multicenter study among long-term disease-free survivors.

PURPOSE: Women undergoing radical cystectomy (RC) and urinary diversion for bladder cancer experience substantial limitations in health-related quality of life (HRQOL). However, the level of discomfort caused by different urinary diversion has been never evaluated in long term survivors. The aim of this multicenter study is to evaluate differences in HRQOL among recurrence-free women undergoing cutaneous ureterostomy (CUS), Bricker's ileal conduit (BK-IC) and Orthotopic neobladder VIP (ONB-VIP) in disease-free females treated with radical cystectomy (RC), with long-term follow up (mean 60.1 months; range 36-122 months). MATERIALS AND METHODS: All consecutively treated female patients from two urological institutions who underwent RC and urinary diversion from January 2000 to December 2008, with no evidence of tumor recurrence at a minimum follow up of 36 months, were included. Patients received the European Organisation for Research and Treatment of Cancer (EORTC) generic (QLQ-C30) and bladder cancer-specific instruments (QLQ-BLM30) and the Functional Assessment of Cancer Therapy for Bladder Cancer (FACT-BL). Clinical data and questionnaire results were analyzed in order to evaluate the HRQOL differences among diversion groups. RESULTS: We identified 37 females (median age: 68, range 45-82 years), including 12 status-post CUS, 16 who underwent BK-IC, and 9 who underwent ONB-VIP. Most were healthy (24/37 with no comorbidities, 4/37 Charlson 1-2, 9/37 Charlson 3 or greater - we didn't considered bladder cancer in Charlson evaluation because bladder cancer was the main inclusion criteria). Women undergoing CUS endorsed worse FACT-BL scores compared with BK-IC and ONB-VIP patients, worse HRQOL regarding physical and emotional well-being (p=0.008 and p=0.02, respectively), and a trend toward worse EORTC QLQ-C30 scores for appetite loss and fatigue (p=0.05 for both). CONCLUSIONS: In our study long-term disease-free females treated with CUS endorsed worse HRQOL compared with women who underwent BK-IC or ONB-VIP, mostly due to worse physical and emotional perception of their body image.

The impact of prior TURP on radical prostatectomy surgical margins: a multicenter analysis.

OBJECTIVE: To analyze positive surgical margins (PSM) after radical prostatectomy (RP) in the overall population and in patients previously treated with transurethral resection of the prostate (TURP). MATERIALS AND METHODS: 2,408 patients treated with RP for clinically localized prostate cancer (PCa) were consecutively enrolled in 135 departments. We correlated PSM rates and all preoperative, surgical and pathological features. We stratified the site of PSM as unique or multifocal. Moreover, we analyzed differences between 75 patients who had undergone previous TURP and the remaining 2,333 patients. RESULTS: In the entire study population, we identified 702 patients with PSM (29%). Using univariate analysis, we reported a significant correlation between overall PSM and prostate-specific antigen (PSA), stage cT, biopsy Gleason score, number of biopsy cores, number of positive cores, percentage of positive cores and nerve-sparing approach. PSM proved to be strongly dependent on pT in particular in patients with pT2 PCa. When we compared the data from 75 patients previously treated with TURP and those from 2,333 without previous prostatic surgery, a statistically significant difference in margin localization was found. Moreover, we analyzed the 75 patients mentioned above, stratified in incidental PCa diagnosed at TURP or PCa detected with prostate biopsy for PSA rising during the post-TURP follow-up: no statistical differences were found between the 2 groups regarding margin status, even if PSM were more frequent in incidental PCa with no significance deriving from the stratification for PSM location at the apex or base. CONCLUSION: Men treated with TURP before RP presented an overall incidence of PSM similar to those without previous TURP, but with a higher risk of PSM at the bladder neck and a lower risk of PSM at the prostatic apex.

Use of Solovov-Badenoch principle in treating severe and recurrent vesico-urethral anastomosis stricture after radical retropubic prostatectomy: technique and long-term results.

UNLABELLED: What's known on the subject? and What does the study add? Many different approaches have been used to treat bladder neck strictures and urinary incontinence after radical prostatectomy in the past. Most techniques are highly invasive and carry a high risk of complications. The present study describes the use of the Solovov-Badenoch 'pull-through urethroplasty' as well as artificial urinary sphincter implantation. OBJECTIVE: • To report our experience in the management of patients with combined urinary incontinence and stricture after radical prostatectomy with a two-step approach: urethroplasty with a 'pull-through' technique after the Solovov-Badenoch principle; and artificial urinary sphincter (AUS) insertion after 8-10 months. PATIENTS AND METHODS: • We retrospectively evaluated a cohort of 11 patients treated between September 2001 and January 2010. RESULTS: • There were no intraoperative complications in either procedure. • After urethroplasty one patient was unable to empty the bladder with complete urine retention without urethral stricture (treatment failure). • At 6 months after the urethroplasty 10 patients were completely incontinent and received AUS. • One previously irradiated patient developed urethral erosion 6 months after AUS implantation and underwent complete removal of the device. • After a mean (range) follow-up of 65 (19-119) months, nine patients (81.8%) were continent with no post-void residual urine and a perfectly functioning AUS. CONCLUSION: • Our experience with a two-step approach (combined suprapubic/transperineal redo anastomosis and AUS placement) shows that redo vesico-urethral anastomosis is easier than pure transperineal approaches with good results in restoring patency and that the transperineal step provides a dedicated operative field for AUS implantation with reduced risks of perioperative complications.

Chromophobe renal cell carcinoma (RCC): oncological outcomes and prognostic factors in a large multicentre series.

UNLABELLED: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? About 80% of RCCs have clear cell histology, and consistent data are available about the clinical and histological characteristics of this histological subtype. Conversely, less attention has been dedicated to the study of non-clear cell renal tumours Specifically, published data show that chromophobe RCC (ChRCC) have often favourable pathological stages and better nuclear grades as well as a lower risk of metastasizing compared with clear cell RCC (ccRCC). Patients with ChRCC were shown to have significantly higher cancer-specific survival (CSS) probabilities compared with ccRCC. However, an independent prognostic role of RCC histotype was not confirmed in some large multicenter series and only a few studies have focused on the oncological outcomes of ChRCC. The present study is one of the few to evaluate cancer-related outcomes of ChRCC and represents to our knowledge the largest series of ChRCCs. Consequently, the present findings may assist in elucidating the natural history of surgically treated ChRCC. The present study confirms that ChRCCs have good prognosis and a low tendency to progress and metastasize. Only 1.3% of patients presented with distant metastases at diagnosis, and the 5- and 10-year CSS were 93% and 88.9%, respectively. However, although ChRCCs are generally characterised by an excellent prognosis, we observed that patients with locally advanced or metastatic cancers as well as those with sarcomatoid differentiation have a poor outcome. The study also investigated prognostic factors for recurrence-free survival (RFS) and CSS for this RCC histotype. The definition of outcome predictors can be useful for patient counselling, planning of follow-up strategies, and patient selection for clinical trials. In the present study, gender, clinical T stage, pathological T stage, and presence of sarcomatoid differentiation were significantly associated with RFS and CSS at multivariable analysis. We also identified N/M stage as an independent predictor of CSS. Notably, as Fuhrman grade was not an independent predictor of cancer-related outcomes, the present study confirms that this histological variable is not a reliable prognostic factor for ChRCC. OBJECTIVES: To investigate cancer-related outcomes of chromophobe renal cell carcinoma (ChRCC) in a large multicentre dataset. To determine prognostic factors for recurrence-free survival (RFS) and cancer-specific survival (CSS) for this RCC histological type. PATIENTS AND METHODS: In all, 291 patients with ChRCC were identified from a multi-institutional retrospective database including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007. Univariable and multivariable Cox regression models were used to identify prognostic factors predictive of RFS and CSS after surgery for ChRCC. RESULTS: At a median follow-up of 44 months, 25 patients (8.6%) had disease recurrence and 18 patients (6.2%) died from disease. The 5-year RFS and CSS rates were 89.3% and 93%, respectively. Gender (P= 0.014), clinical T stage (P= 0.017), pathological T stage (P= 0.003), and sarcomatoid differentiation (P= 0.032) were independent predictors of RFS at multivariable analysis. For CSS, there was an independent prognostic role for gender (P= 0.032) and T stage (P= 0.019) among the clinical variables and for T stage (P= 0.016), N/M stage (P= 0.023), and sarcomatoid differentiation (P= 0.015) among the pathological variables. CONCLUSIONS: Patients with ChRCC have a low risk of tumour progression, metastasis, and cancer-specific death. Patient gender, clinical and pathological tumour stage, and sarcomatoid differentiation are significant predictors of RFS and CSS for ChRCC.

Prognostic factors in a large multi-institutional series of papillary renal cell carcinoma.

OBJECTIVES: To investigate cancer-related outcomes and prognostic factors of papillary renal cell carcinoma (pRCC) in a large multicentre data set. Oncological outcome and prognostic factors of pRCC have been limitedly evaluated in comparison with the most common RCC subtype, clear cell RCC. PATIENTS AND METHODS: From a multicentre retrospective database, including 5463 patients who were surgically treated for RCC at 16 Italian academic centres between 1995 and 2007, 577 patients with pRCC were identified. Univariable and multivariable Cox regression models were performed to identify prognostic factors predictive of recurrence-free survival (RFS) and cancer-specific survival (CSS) after surgery. RESULTS: At a median (interquartile range) follow-up of 39.2 (21.7-72) months, 81 (14%) patients had experienced disease progression and 63 (11%) patients had died from disease; the 5-year RFS estimate was 85.5%. In multivariable analysis, pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.9; P= 0.007) and Fuhrman nuclear grade (pooled P= 0.039) were all independent predictors of RFS; the 5-year CSS estimate was 87.9%. In Cox multivariable analysis, an independent predictive role was reconfirmed for mode of presentation (pooled P= 0.038), pathological N stage (pooled P < 0.001), M stage (hazard ratio, 2.4; P= 0.049) and Fuhrman nuclear grade (pooled P= 0.037). CONCLUSIONS: Patients with pRCC have a low risk of tumour recurrence and cancer-related death after surgery. Fuhrman nuclear grade was found to be a stronger predictor of both RFS and CSS, whereas only a non-statistically significant trend was found for the 2009 pathological T stage.

Prognostic role of tumour multifocality in renal cell carcinoma.

UNLABELLED: What's known on the subject? and What does the study add? In RCC about 5% of the patients presented multifocal disease. Prevalence of tumour multifocality was associated with a higher percentage of symptomatic RCC, higher pathological TNM stages, higher tumour grade and higher prevalence of tumour necrosis. Although in univariable analysis multifocal tumours had lower probability of CSS, tumour multifocality did not retain an independent predictive role in multivariable analysis. Patient age at surgery, gender, mode of presentation, pathological N stage and presence of metastases were independent predictors of CSS in multivariable analyses. OBJECTIVE: • To evaluate the prevalence and the prognostic role of multifocality in a large multi-institutional series of patients who underwent radical or partial nephrectomy for renal cell carcinoma (RCC). METHODS: • We retrospectively collected the data of 5378 patients who were surgically treated for RCC in 16 academic centres involved in the Surveillance and Treatment Update Renal Neoplasms (SATURN) project. • Univariable and multivariable Cox regression models addressed time to cancer-specific survival (CSS) after surgery. RESULTS: • Tumour multifocality was identified in 249 patients (5%). The median follow-up of the whole cohort was 42 months. At last follow-up, 786 (14.6%) were dead of cancer and 336 (6.2%) had experienced non-cancer-related death. • The 5- and 10-year CSS estimates were 84.1% and 77.3%, respectively, in patients with monofocal RCC, compared with 71.1% and 63.6%, respectively, in patients with multifocal disease (P < 0.001). • In univariable Cox regression analysis, tumour multifocality was significantly associated with CSS (hazard ratio [HR]= 1.83; P < 0.001). • On multivariate Cox regression analysis adjusted for the effects of other covariates, tumour multifocality did not retain an independent predictive value (HR = 1.24; P= 0.291). CONCLUSIONS: • In the present multi-institutional collaboration, about 5% of the patients presented multifocal RCC. • The presence of multifocal cancer was associated with some unfavourable clinical and pathological features. • Although in univariable analysis multifocal tumours had lower CSS probabilities, tumour multifocality did not retain an independent predictive role in multivariable analysis, once adjusted for the effect of the other clinical and pathological covariates.

Elective partial nephrectomy is equivalent to radical nephrectomy in patients with clinical T1 renal cell carcinoma: results of a retrospective, comparative, multi-institutional study.

OBJECTIVE: To compare the oncological outcomes of patients who underwent elective partial nephrectomy (PN) or radical nephrectomy (RN) for clinically organ-confined renal masses ≤7 cm in size (cT1). PATIENTS AND METHODS: The records of 3480 patients with cT1N0M0 disease were extracted from a multi-institutional database and analyzed retrospectively. RESULTS: In patients who underwent PN, the risk of clinical understaging was 3.2% in cT1a cases and 10.6% in cT1b cases. With regard to the cT1a patients, the 5- and 10-year cancer-specific survival (CSS) estimates were 94.7% and 90.4%, respectively, after RN and 96.1% and 94.9%, respectively, after PN (log-rank test: P = 0.01). With regard to cT1b patients, the 5-year CSS probabilities were 92.6% after RN and 90% after PN, respectively (log-rank test: P = 0.89). Surgical treatment failed to be an independent predictor of CSS on multivariable analysis, both for cT1a and cT1b patients. Interestingly, PN was oncologically equivalent to RN also in patients with pT3a tumours (log-rank test: P = 0.91). CONCLUSIONS: Elective PN is not associated with an increased risk of recurrence and cancer-specific mortality in both cT1a and cT1b tumours. Data from the present study strongly support the use of partial nephrectomy in patients with clinically T1 tumours, according to the current recommendations of the international guidelines.

The waiting time for prostate cancer treatment in Italy: analysis from the PROS-IT CNR Study.

BACKGROUND: Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. METHODS: Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. RESULTS: The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. CONCLUSIONS: In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.

Simple enucleation is equivalent to traditional partial nephrectomy for renal cell carcinoma: results of a nonrandomized, retrospective, comparative study.

PURPOSE: The excision of the renal tumor with a substantial margin of healthy parenchyma is considered the gold standard technique for partial nephrectomy. However, simple enucleation showed excellent results in some retrospective series. We compared the oncologic outcomes after standard partial nephrectomy and simple enucleation. MATERIALS AND METHODS: We retrospectively analyzed 982 patients who underwent standard partial nephrectomy and 537 who had simple enucleation for localized renal cell carcinoma at 16 academic centers between 1997 and 2007. Local recurrence, cancer specific survival and progression-free survival were the main outcomes of this study. The Kaplan-Meier method was used to calculate survival functions and differences were assessed with the log rank statistic. Univariable and multivariable Cox regression models addressed progression-free survival and cancer specific survival. RESULTS: Median followup of the patients undergoing traditional partial nephrectomy and simple enucleation was 51 ± 37.8 and 54.4 ± 36 months, respectively (p = 0.08). The 5 and 10-year progression-free survival estimates were 88.9 and 82% after standard partial nephrectomy, and 91.4% and 90.8% after simple enucleation (p = 0.09). The 5 and 10-year cancer specific survival estimates were 93.9% and 91.6% after standard partial nephrectomy, and 94.3% and 93.2% after simple enucleation (p = 0.94). On multivariable analysis the adopted nephron sparing surgery technique was not an independent predictor of progression-free survival (HR 0.8, p = 0.55) and cancer specific survival (HR 0.7, p = 0.53) when adjusted for the effect of the other covariates. CONCLUSIONS: To our knowledge this is the first multicenter, comparative study showing oncologic equivalence of standard partial nephrectomy and simple enucleation.

Patients' desire to preserve sexual activity and final decision for a nerve-sparing approach: results from the MIRROR (Multicenter Italian Report on Radical Prostatectomy Outcomes and Research) Study.

INTRODUCTION: Preservation of sexual function after surgery represents a major issue for patients undergoing radical prostatectomy (RP). AIM: To investigate determinants of patients' desire to preserve sexual activity before RP and surgeons' final decision to perform a nerve-sparing RP (NSRP). METHODS: Overall, 2,408 prostate cancer patients, candidates to RP, from 136 urologic departments across the Italian territory were evaluated in a multicenter prospective observational study. All patients underwent RP, according to single-center indications and procedures. MAIN OUTCOME MEASURES: Age, body mass index, previous benign prostatic hyperplasia history, preoperative tumor characteristics, quality of life through the Short Form Health Survey (SF-12), and the University of California Los Angeles Prostate Cancer Index (UCLA-PCI), erectile function through the International Index of Erectile Function (IIEF-5), desire to preserve sexual activity, NS operative outcomes, and surgical margins status were recorded. RESULTS: Overall, 1,667 were interested to preserve sexual activity. Age, physical component summary of SF12 (PCS-12), sexual function score of UCLA-PCI, and IIEF-5 score were the main determinants of such interest. Only 1,246 patients were suitable for a NSRP according to guidelines. Surgeons performed a non-NSRP (NNSRP) in 1,234 patients, a unilateral NSRP in 318 and a bilateral NSRP in 856. Age, bioptical Gleason score, percentage of positive cores, PCS-12, and patient's desire to preserve sexual activity were the main determinants of final decision for a NSRP. Surgeons performed a NSRP in 424 not suitable and in 121 not interested patients. Positive surgical margins in not suitable patients submitted to NSRP were not higher if compared to that obtained after NNSRP in the same subgroup. Limits include lack of oncological and functional follow-up. CONCLUSIONS: Most patients are interested to preserve sexual activity. Discrepancies exist among patients' preferences, guidelines' indications, and surgeon's final decision.

Are referral centers for non-muscle-invasive bladder cancer compliant to EAU guidelines? A report from the vesical antiblastic therapy Italian study.

INTRODUCTION: Adherence to international guidelines is viewed as a prerequisite for optimal medical care delivery. Previously reported surveys for non-muscle-invasive bladder cancer (NMIBC) employed mailed questionnaires to urologists or patients resulting in conflicting degrees of agreement with existing guidelines. In the current study, contemporary information on the management of NMIBC was generated from a sample of italian centers. PATIENTS AND METHODS: Eight Italian referral centers for the treatment of NMIBC were asked to collect information relative to all consecutive patients with a histology-proven NMIBC undergoing a transurethral resection from January 1 to March 31, 2009. The primary study objective was to verify the level of adherence of disease management with European guidelines. RESULTS: 344 patients resulted in being evaluable. 49.2% of high-risk patients underwent a repeat transurethral resection. Bacillus Calmette-Guérin was employed in 35% of cases, while chemotherapy was in 22%. An early single regimen was adopted in 136 patients and only in 1 out of 3 low-risk patients. High-risk NMIBC received bacillus Calmette-Guérin and chemotherapy as first-line therapy in 66 and 12.5% respectively. After 3 months, cystoscopy had been reported for 82.5% of patients with a recurrence rate of 13%. CONCLUSION: Adherence of Italian Institutions to EAU guidelines was optimal when reporting baseline variables. Significant degrees of discrepancy emerged in treatment choices.