Comprehensive long-term assessment of outcomes following robot-assisted partial nephrectomy for renal cell carcinoma: the ROMe's achievement and its predicting nomogram.

BACKGROUND: We proposed a new tool (named ROMe's) to summarize long-term outcomes after partial nephrectomy (PN), identified its predictors and generated a predicting nomogram. METHODS: A retrospective analysis of a multicenter dataset of patients with non-metastatic pT1-3a renal cell carcinoma was performed. Baseline demographic, clinical, pathologic and perioperative data were collected. ROMe's was defined as the concomitant lack of cancer-recurrences, death and newly onset Chronic Kidney Disease (CKD), at long term follow-up. Kaplan-Meier method investigated the predictive role of Trifecta on ROMe's achievement. Univariable and multivariable Cox regression analyses identified its predictors. A nomogram was generated and its accuracy was quantified using concordance index (CI). A calibration plot was obtained with 200 bootstraps resampling to explore nomogram performance at 5 years and decision curve analyses (DCA) assessed the net benefit of the model at 12, 36 and 60 months. RESULTS: We included 927 patients. The rates of ROMe's were 82%, 72% and 56% at 1, 3 and 5 years follow-up. At Kaplan-Meier analysis, patients who achieved Trifecta displayed a significantly higher probability of ROMe's (log rank P<0.001). Young age (OR=0.982; P=0.001), low RENAL score (OR=0.86; P=0.037), high preoperative filtration rate (OR=1.02; P<0.001) and Trifecta achievement (OR=2.03; P=0.015), were independent predictors of ROMe's. The nomogram showed a CI of 0.76 at 60 months. The 5-years calibration plot confirmed a good discrimination accuracy (0.74); on DCA, the net benefit of using the model was evident for probabilities >30%. CONCLUSIONS: We conceived a triad to summarize the main long-term oncologic and functional outcomes after PN and generated a predicting nomogram.

Decision-making tools in prostate cancer: from risk grouping to nomograms.

INTRODUCTION: Prostate cancer (PCa) is the most common solid neoplasm and the second leading cause of cancer death in men. After the Partin tables were developed, a number of predictive and prognostic tools became available for risk stratification. These tools have allowed the urologist to better characterize this disease and lead to more confident treatment decisions for patients. The purpose of this study is to critically review the decision-making tools currently available to the urologist, from the moment when PCa is first diagnosed until patients experience metastatic progression and death. EVIDENCE ACQUISITION: A systematic and critical analysis through Medline, EMBASE, Scopus and Web of Science databases was carried out in February 2016 as per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The search was conducted using the following key words: "prostate cancer," "prediction tools," "nomograms." EVIDENCE SYNTHESIS: Seventy-two studies were identified in the literature search. We summarized the results into six sections: Tools for prediction of life expectancy (before treatment), Tools for prediction of pathological stage (before treatment), Tools for prediction of survival and cancer-specific mortality (before/after treatment), Tools for prediction of biochemical recurrence (before/after treatment), Tools for prediction of metastatic progression (after treatment) and in the last section biomarkers and genomics. CONCLUSIONS: The management of PCa patients requires a tailored approach to deliver a truly personalized treatment. The currently available tools are of great help in helping the urologist in the decision-making process. These tests perform very well in high-grade and low-grade disease, while for intermediate-grade disease further research is needed. Newly discovered markers, genomic tests, and advances in imaging acquisition through mpMRI will help in instilling confidence that the appropriate treatments are being offered to patients with prostate cancer.

Monophasic Synovial Sarcoma of Prostatic Fascia: Case Report and Literature Review.

Synovial sarcoma (SS) primarily occurs in the para-articular soft tissue of the lower extremities in young adults and it is extremely rare in the prostatic region. We report a case of a 46-year-old man who presented with urinary retention. Pelvic ultrasound (US) examination, computed tomography (CT), and magnetic resonance imaging (MRI) demonstrated an 8.5 cm mass that appeared to originate in the prostatic fascia of the right lobe. Preoperative prostatic ultrasound transrectal needle biopsy revealed mesenchymal neoplastic tissue. Patient underwent surgery. The final pathologic findings were consistent with the diagnosis of monophasic synovial sarcoma.

[How to biopsy only men with high grade prostate cancer]. / Come biopsiare solo i paziente con tumore prostatico ad alto grado.

INTRODUCTION: Fuzzy logic and Artificial Neural Networks (ANN) are complementary technologies that together generate neuro-fuzzy system. The aim of our study is to compare 2 models for predicting the presence of high-grade prostate cancer (Gleason score 7 or more). METHODS: We evaluated data from 1000 men with PSA less than 50 ng/mL, who underwent prostate biopsy. A prostate cancer was found in 313 (31%), and in 172 (17.2%) we detected high-grade prostate cancer. With those data, we developed 2 Co-Active Neuro-Fuzzy Inference Systems to predict the presence of high-grade prostate cancer. The first model had four input neurons (PSA, free PSA percentage [%freePSA], PSA density, and age) and the second model had three input neurons (PSA, %freePSA, and age). RESULTS: The model with four input neurons (PSA, %freePSA, PSA density, and age) showed better performances than the one with three input neurons (PSA, %freePSA, and age). In fact the average testing error was 0.42 for the model with four input neurons and 0.44 for the other model. CONCLUSIONS: The addition of PSA density to the model has allowed to obtain better results for the diagnosis of high grade prostate cancer.

Early exploratory intervention in scrotal trauma.

INTRODUCTION: The aim of our study is to assess the incidence of the surgical approach in scrotal trauma. MATERIALS AND METHODS: We retrospectively assessed both penetrating and blunt cases of scrotal trauma observed from 2002 to 2012. For each case we considered various parameters such as the age of the patient, whether the type of trauma was penetrating or blunt, whether or not a surgical approach was taken, whether or not there were polytrauma, whether or not an orchiectomy was performed, and how many days had elapsed since the first urological observation of the trauma. RESULTS: 43 cases of scrotal trauma were assessed, of which 39 were blunt traumas (90%) and four penetrating traumas (10%). The median age of all patients was 29 years (range 4-88). Of these patients, eight underwent surgical procedures, of which three were cases of penetrating scrotal trauma and five were cases of blunt trauma, with an average age of 20. We only found it necessary to carry out an orchiectomy in two of these patients, of which one was after penetrating trauma and the other after blunt trauma. Most of the blunt traumas did not require surgery (8 versus 35, p<0.05). CONCLUSIONS: In our case studies, in the majority of cases early exploratory intervention in scrotal trauma allows the testicle to be saved in its entirety or at least in part.

Can a Gleason 6 or Less Microfocus of Prostate Cancer in One Biopsy and Prostate-Specific Antigen Level <10 ng/mL Be Defined as the Archetype of Low-Risk Prostate Disease?

Prostate cancer (PC) remains a cause of death worldwide. Here we investigate whether a single microfocus of PC at the biopsy (graded as Gleason 6 or less, ≤5% occupancy) and the PSA <10 ng/mL can define the archetype of low-risk prostate disease. 4500 consecutive patients were enrolled. Among them, 134 patients with a single micro-focus of PC were followed up, and the parameters influencing the biochemical relapse (BR) were analysed. Out of 134 patients, 94 had clinically significant disease, specifically in 74.26% of the patients with PSA <10 ng/mL. Positive surgical margins and the extracapsular invasion were found in 29.1% and 51.4% patients, respectively. BR was observed in 29.6% of the patients. Cox regression evidenced a correlation between the BR and Gleason grade at the retropubic radical prostatectomy (RRP), capsular invasion, and the presence of positive surgical margins. Multivariate regression analysis showed a statistically significant correlation between the presence of surgical margins at the RRP and BR. Considering a single micro-focus of PC at the biopsy and PSA serum level <10 ng/mL, clinically significant disease was found in 74.26% patients and only positive surgical margins are useful for predicting the BR.

[PLFT and TUMT long-term clinical results in Italy]. / Risultati a lungo termine del trattamento dell'adenoma prostatico mediante TUMT-PLFT.

Microwaves are electromagnetic radiations with wavelengths ranging from 300 MHz (0.3 GHz) and 300 GHz. Microwaves treatment reduces prostate tissue using the heat produced by microwaves. When the tissue absorbs the energy from the microwaves it coagulates and tissue necrosis occours. During hyperthermia the intraprostatic temperatures reached 40-45 °C with symptomatic improvement due to destruction of the alpha-adrenergic nerve fibers around the prostate. The term 'thermotherapy' was therefore coined to describe treatment temperatures above 45°C and hyperthermia for those below this level. Unlike thermotherapy, high-energy (thermotherapy) can achieve temperatures greater than 70°C (158°F), causing thermoablation of prostatic tissue. The authors report their experience with PLFT over a period of 8 years. They describe the technique of the treatment, the goal and its results. Many of these patients, however, were older, had a larger prostate volume, and had more surgical comorbidities, making this subset more likely to benefit from a minimally invasive option. With PLFT-TUMT, patients have a less-invasive therapy, with a catheter-free rate of 82-91% in selected patients, although the majority must also continue medical therapy.

Evaluation of prostate specific antigen acceleration for prostate cancer diagnosis.

PURPOSE: Prostate specific antigen acceleration can be calculated as the slope of log prostate specific antigen vs time, where log is the natural logarithm. We determined the best interval in which prostate specific antigen acceleration can be calculated with the best result in terms of specificity and sensitivity for prostate cancer diagnosis. MATERIALS AND METHODS: Entered in the study were 741 men who underwent transrectal ultrasound guided prostate biopsy with 12 or more cores and at least 3 prior consecutive prostate specific antigen measurements in at least 365 days. Prostate specific antigen acceleration was calculated as the slope of log prostate specific antigen vs time using a minimum of 3 prostate specific antigen measurements. Acceleration was evaluated at different intervals, including within 1 year (365 days), 2 years (730 days), 3 years (1,095 days), 4 years (1,460 days), 5 years (1,825 days) and 6 years (2,190 days) before the last measurement. RESULTS: A total of 255 cancers (34.4%) were found. On ROC analysis the AUC of prostate specific antigen acceleration (0.728, 95% CI 0.694-0.760) was better than that of prostate specific antigen, prostate specific antigen velocity and prostate specific antigen doubling time. The highest AUC of prostate specific antigen kinetics was for prostate specific antigen acceleration calculated within 3 to 4 years (731 to 1,460 days) before the last measurement. CONCLUSIONS: Three or more prostate specific antigen measurements within 3 to 4 years (731 to 1,460 days) before the last measurement enabled more accurate calculation of prostate specific antigen acceleration than measurement within 1 to 2 years (0 to 730 days).

Phase III, randomised, multicentre trial of maintenance immunotherapy with low-dose interleukin-2 and interferon-alpha for metastatic renal cell cancer.

This is the first phase III randomised trial to evaluate maintenance immunotherapy in metastatic renal cell cancer (mRCC). Patients were randomised to receive treatment with a 4-week cycle of subcutaneous low doses IL-2 + IFN in months 1, 3 and 5, and then every 3 months until the first documented disease progression (arm A, suspension), or the same regimen, with chronic maintenance of immunotherapy, regardless of tumour response, until death or intolerable toxicity (arm B, maintenance). The primary endpoint was overall survival (OS); secondary endpoints were time from first progression to death (TFPTD) and tolerability. One hundred and eighty-three patients were enrolled between January 1998 and November 2003. After a median follow-up of 53.9 months, response rate, median OS and median TFPTD were 14.7% (6.3% CR) versus 11.3% (5.5% CR), 14 versus 14 months, 6 versus 5 months, in arms A and B, respectively with no significant differences between the groups. Cox regression analysis showed that the use of chemotherapy after first progression (HR 0.54; 95% CI 0.35-0.86; p = 0.008), PS = 0 (HR 0.53; 95% CI 0.35-0.81; p = 0.001) and female gender (HR 0.63; 95% CI 0.41-0.98; p = 0.038) were significantly associated with a longer TFPTD; treatment arm was not significant (HR 0.88; 95% CI 0.60-1.31; p = 0.54). Toxicity was mainly limited to WHO grades 1 or 2. Chronic maintenance immunotherapy after disease progression is feasible, but does not significantly increase OS or the TFPTD.

A novel nomogram to predict the probability of prostate cancer on repeat biopsy.

PURPOSE: We developed a predictive model that incorporates clinical data and prostate specific antigen kinetic from general practice to detect prostate cancer in patients with a previously negative prostate biopsy. MATERIALS AND METHODS: From January 2001 to January 2007 data on 419 men who underwent repeat prostate biopsy with 12 or more cores were used to develop the nomogram. From February 2007 to June 2007 data on 63 men with the same criteria were used to validate the nomogram. The factors that we evaluated for the risk of a positive repeat prostate biopsy were patient age, digital rectal examination findings, total prostate specific antigen, the free-to-total prostate specific antigen ratio, prostate specific antigen density and slope, and previous high grade prostatic intraepithelial neoplasia. RESULTS: On multivariate logistic regression all factors except age and prostate specific antigen showed significant ability to predict the outcome of 12-core repeat prostate biopsy. In the validation group the AUC of the predicted results from the model was 0.856 (95% CI 0.744-0.931), better than that of prostate specific antigen, the free-to-total prostate specific antigen ratio, and prostate specific antigen density and slope (p <0.05). CONCLUSIONS: We successfully developed an accurate model to predict the outcome of repeat prostate biopsy. Adding the free-to-total prostate specific antigen ratio, digital rectal examination, prostate specific antigen and slope, and history of high grade prostatic intraepithelial neoplasia sharply improves the accuracy of our model.

Optimal measure of PSA kinetics to identify prostate cancer.

OBJECTIVES: To compare different tools for evaluate prostate-specific antigen (PSA) kinetics before prostate biopsy, such as PSA velocity, PSA slope, natural logarithm PSA slope (lnPSA slope), and PSA doubling time (PSADT). METHODS: This study was conducted involving 325 male patients evaluated with transrectal ultrasound-guided biopsy of prostate. Patients with at least three consecutive PSA measurements taken in at least 24 months entered in the study. We estimated PSA slope from the slope of the least squares regression line fit to PSA versus time in years; PSA velocity was calculated as the running average of the rate of change during at least three consecutive assays. The acceleration of PSA (lnPSA slope) was calculated as the slope of lnPSA versus time, where ln is the natural logarithm. PSADT was calculated using the formula: PSADT = ln 2/(lnPSA slope). RESULTS: We found a total of 74 cancers at the ultrasound guided prostate biopsies. At the receiver operating characteristic (ROC) analysis, lnPSA slope (area under the curve [AUC], 0.793) evidenced better results than PSA (AUC, 0.585; P <0.001), PSA velocity (AUC, 0.734; P <0.009), PSA slope (AUC, 0.752; P <0.043), and PSADT (AUC, 0.516; P <0.001). CONCLUSIONS: The results for PSA, PSA velocity, PSA slope, and lnPSA slope were significantly higher in patients with prostate cancer than in controls. The results of the present study suggest that lnPSA slope may be useful for prostate cancer diagnosis. At the ROC analyses, the lnPSA slope AUC was better than that of PSA, PSA velocity, PSA slope, and PSADT.

Neuro-fuzzy system for prostate cancer diagnosis.

OBJECTIVES: To develop a neuro-fuzzy system to predict the presence of prostate cancer. Neuro-fuzzy systems harness the power of two paradigms: fuzzy logic and artificial neural networks. We compared the predictive accuracy of our neuro-fuzzy system with that obtained by total prostate-specific antigen (tPSA) and percent free PSA (%fPSA). METHODS: The data from 1030 men (both outpatients and hospitalized patients) were used. All men had a tPSA level of less than 20 ng/mL. Of the 1030 men, 195 (18.9%) had prostate cancer. A neuro-fuzzy system was developed using the coactive neuro-fuzzy inference system model. RESULTS: The mean area under the receiver operating characteristic curve for the neuro-fuzzy system output was 0.799 +/- 0.029 (95% confidence interval 0.760 to 0.835), for tPSA, it was 0.724 +/- 0.032 (95% confidence interval 0.681 to 0.765), and for %fPSA, 0.766 +/- 0.024 (95% confidence interval 0.725 to 0.804). Furthermore, pairwise comparison of the area under the curves evidenced differences among %fPSA, tPSA, and neuro-fuzzy system's output (tPSA versus neuro-fuzzy system's output, P = 0.008; %fPSA versus neuro-fuzzy system's output, P = 0.032). The comparison at 95% sensitivity showed that the neuro-fuzzy system had the best specificity (31.9%). CONCLUSIONS: This study presented a neuro-fuzzy system based on both serum data (tPSA and %fPSA) and clinical data (age) to enhance the performance of tPSA to discriminate prostate cancer. The predictive accuracy of the neuro-fuzzy system was superior to that of tPSA and %fPSA.

Optimum PSA reflex-range.

OBJECTIVE: Aim of this study was to evaluate different decision strategies based on variations in the cut-off value of percent free PSA and in the range of total PSA values (reflex range) in which free PSA testing was applied. We compared these strategies to conventional total PSA testing by determining which strategies would provide a maximum decrease in unnecessary biopsies with a minimum number of additional undetected cancers. MATERIALS AND METHODS: This retrospective study was conducted with 807 patients who were referred to transrectal ultrasound biopsies for elevated serum PSA levels or for abnormal digital rectal examination. Overall 156 patients were affected by primary prostate cancer (CaP), 651 were controls without prostate cancer (benign prostatic hypertrophy, prostatic intraepithelial neoplasm, prostatitis or normal prostatic gland). RESULTS: Total PSA was significantly higher (F=4.93; p<0.0001) and percent free PSA was significantly lower in cancer patients than in controls (F=2.16; p<0.0001). Sensitivity, specificity and the positive likelihood ratio (LR+) of PSA and percent free PSA have been calculated for several total PSA intervals: PSA 4-10 ng/ml, 3-10 ng/ml, 3-20 ng/ml, 2-10 ng/ml, 2-20 ng/ml. These data suggest that in the reflex range 2-10 ng/ml there are the best results. On ROC comparison restricted to men with total PSA between 2 and 10 ng/ml, percent free PSA also had a higher area under the curve than total PSA (AUC 0.7452 for free percent PSA; 0.6267 for total PSA: p = 0.0059). CONCLUSIONS: The PSA revolution that occurred over the previous 2 decades has positively impacted the detection of prostate cancer. Percent free PSA improves specificity, at the beginning the percent free PSA was used only in the gray zone 4-10 ng/ml. Analyzing our data, we confirm that the usefulness of percent free PSA in prostate cancer diagnosis increases, enlarging the reflex range. Our best result is obtained in the reflex range 2-10 ng/ml using a percent free PSA cut-off of 22%.