Multiparametric MRI-based 5-year Risk Prediction Model for Biochemical Recurrence of Prostate Cancer after Radical Prostatectomy.

Background Current predictive tools to estimate the risk of biochemical recurrence (BCR) after treatment of prostate cancer do not consider multiparametric MRI (mpMRI) information. Purpose To develop a risk prediction tool that considers mpMRI findings to assess the risk of 5-year BCR after radical prostatectomy. Materials and Methods In this retrospective single-center analysis in 1459 patients with prostate cancer who underwent mpMRI before radical prostatectomy (in 2012-2015), the outcome of interest was 5-year BCR (two consecutive prostate-specific antigen [PSA] levels > 0.2 ng/mL [0.2 µg/L]). Patients were randomly divided into training (70%) and test (30%) sets. Kaplan-Meier plots were applied to the training set to estimate survival probabilities. Multivariable Cox regression models were used to test the relationship between BCR and different sets of exploratory variables. The C-index of the final model was calculated for the training and test sets and was compared with European Association of Urology, University of California San Francisco Cancer of the Prostate Risk Assessment, Memorial Sloan-Kettering Cancer Center, and Partin risk tools using the partial likelihood ratio test. Five risk categories were created. Results The median duration of follow-up in the whole cohort was 59 months (IQR, 32-81 months); 376 of 1459 (25.8%) patients had BCR. A multivariable Cox regression model (referred to as PIPEN, and composed of PSA density, International Society of Urological Pathology grade group, Prostate Imaging Reporting and Data System category, European Society of Urogenital Radiology extraprostatic extension score, nodes) fitted to the training data yielded a C-index of 0.74, superior to that of other predictive tools (C-index 0.70 for all models; P ≤ .01) and a median higher C-index on 500 test set replications (C-index, 0.73). Five PIPEN risk categories were identified with 5-year BCR-free survival rates of 92%, 84%, 71%, 56%, and 26% in very low-, low-, intermediate-, high-, and very high-risk patients, respectively (all P < .001). Conclusion A five-item model for predicting the risk of 5-year BCR after radical prostatectomy for prostate cancer was developed and internally verified, and five risk categories were identified. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Aguirre and Ortegón in this issue.

What is the best time for postoperative radiation therapy in pN1 prostate cancer?

We retrospectively compared long-term biochemical recurrence rates (BCR) in pN1 PCa patients that underwent adjuvant radiotherapy (aRT) vs. no aRT/early salvage (esRT) after robot-assisted radical prostatectomy and extended pelvic lymphadenectomy. All PCa pN1 M0 patients treated at a single high-volume center between 2010 and 2020 were analyzed. Patients with <10 LNs yield, or >10 positive LNs, or persistently detectable PSA after RARP were excluded. Kaplan-Meier (KM) plots depicted BCR rates. Multivariable Cox regression models (MCRMs) focused on predictors of BCR. The cumulative incidence plot depicted BCR rates after propensity score (PS) matching (ratio 1:1). 220 pN1 patients were enrolled, 133 (60.4%) treated with aRT and 87 (39.6%) with no-aRT/esRT. aRT patients were older, with higher rates of postoperative ISUP grade group 4-5, and higher rates of pT3b stage. The actuarial BCR was similar (aRT 39.8% vs. no-aRT/esRT 40.2%; p=1). Median time to BCR was 62 vs. 38 months in aRT vs. no-aRT/esRT patients (p=0.001). In MCRMs, patients managed with no-aRT/esRT were associated with higher rates of BCR over time (hazard ratio [HR]: 3.27, p<0.001). ISUP grade group 5 (HR: 2.18, p<0.01) was an independent predictor of BCR. In PS-matched cumulative incidence plots, the BCR rate was significantly higher in the aRT group (76.4 vs. 40.4%; p<0.01). Patients managed with no-aRT/esRT experienced BCR approximately two years before the aRT group. Despite, the important BCR benefit after aRT, this treatment strategy is underused in daily practice.

Identifying the Optimal Number of Neoadjuvant Chemotherapy Cycles in Patients with Muscle Invasive Bladder Cancer.

PURPOSE: We investigated the pathological response rates and survival associated with 3 vs 4 cycles of cisplatin-based neoadjuvant chemotherapy (NAC) in patients with cT2-4N0M0 muscle invasive bladder cancer. MATERIALS AND METHODS: In this cohort study we analyzed clinical data of 828 patients treated with NAC and radical cystectomy between 2000 and 2020. A total of 384 and 444 patients were treated with 3 and 4 cycles of NAC, respectively. Pathological objective response (pOR; ypT0-Ta-Tis-T1 N0), pathological complete response (pCR; ypT0 N0), cancer-specific survival and overall survival were investigated. RESULTS: pOR and pCR were achieved in 378 (45%; 95% CI 42, 49) and 207 (25%; 95% CI 22, 28) patients, respectively. Patients treated with 4 cycles of NAC had higher pOR (49% vs 42%, p=0.03) and pCR (28% vs 21%, p=0.02) rates compared to those treated with 3 cycles. This effect was confirmed on multivariable logistic regression analysis (pOR OR 1.46 p=0.008, pCR OR 1.57, p=0.007). On multivariable Cox regression analysis, 4 cycles of NAC were significantly associated with overall survival (HR 0.68; 95% CI 0.49, 0.94; p=0.02) but not with cancer-specific survival (HR 0.72; 95% CI 0.50, 1.04; p=0.08). CONCLUSIONS: Four cycles of NAC achieved better pathological response and survival compared to 3 cycles. These findings may aid clinicians in counseling patients and serve as a benchmark for prospective trials. Prospective validation of these findings and assessment of cumulative toxicity derived from an increased number of cycles are needed.

Repeat MRI during active surveillance: natural history of prostatic lesions and upgrading rates.

OBJECTIVES: To assess upgrading rates in patients on active surveillance (AS) for prostate cancer (PCa) after serial multiparametric magnetic resonance imaging (mpMRI). METHODS: We conducted a retrospective analysis of 558 patients. Five different criteria for mpMRI progression were used: 1) a Prostate Imaging Reporting and Data System (PI-RADS) score increase; 2) a lesion size increase; 3) an extraprostatic extension score increase; 4) overall mpMRI progression; and 5) the number of criteria met for mpMRI progression (0 vs 1 vs 2-3). In addition, two definitions of PCa upgrading were evaluated: 1) International Society of Urological Pathology Grade Group (ISUP GG) ≥2 with >10% of pattern 4 and 2) ISUP GG ≥ 3. Estimated annual percent changes methodology was used to show the temporal trends of mpMRI progression criteria. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of mpMRI progression criteria were also analysed. Multivariable logistic regression models tested PCa upgrading rates. RESULTS: Lower rates over time for all mpMRI progression criteria were observed. The NPV of serial mpMRI scans ranged from 90.5% to 93.5% (ISUP GG≥2 with >10% of pattern 4 PCa upgrading) and from 98% to 99% (ISUP GG≥3 PCa upgrading), depending on the criteria used for mpMRI progression. A prostate-specific antigen density (PSAD) threshold of 0.15 ng/mL/mL was used to substratify those patients who would be able to skip a prostate biopsy. In multivariable logistic regression models assessing PCa upgrading rates, all five mpMRI progression criteria achieved independent predictor status. CONCLUSION: During AS, approximately 27% of patients experience mpMRI progression at first repeat MRI. However, the rates of mpMRI progression decrease over time at subsequent mpMRI scans. Patients with stable mpMRI findings and with PSAD < 0.15 ng/mL/mL could safely skip surveillance biopsies. Conversely, patients who experience mpMRI progression should undergo a prostate biopsy.

Current application of the enhanced recovery after surgery protocol for patients undergoing radical cystectomy: lessons learned from European excellence centers.

PURPOSE: There is no consensus on which items of Enhanced Recovery After Surgery (ERAS) should and should not be implemented in radical cystectomy (RC). The aim of this study is to report current practices across European high-volume RC centers involved in ERAS. METHODS: Based on the recommendations of the ERAS society, we developed a survey with 17 questions that were validated by the Young Academic Urologists-urothelial group. The survey was distributed to European expert centers that implement ERAS for RC. Only one answer per-center was allowed to keep a representative overview of the different centers. RESULTS: 70 surgeons fulfilled the eligibility criteria. Of note, 28.6% of surgeons do not work with a referent anesthesiologist and 25% have not yet assessed the implementation of ERAS in their center. Avoiding bowel preparation, thromboprophylaxis, and removal of the nasogastric tube were widely implemented (> 90%application). On the other hand, preoperative carbohydrate loading, opioid-sparing anesthesia, and audits were less likely to be applied. Common barriers to ERAS implementation were difficulty in changing habits (55%), followed by a lack of communication across surgeons and anesthesiologist (33%). Responders found that performing a regular audit (14%), opioid-sparing anesthesia (14%) and early mobilization (13%) were the most difficult items to implement. CONCLUSION: In this survey, we identified the ERAS items most and less commonly applied. Collaboration with anesthesiologists as well as regular audits remain a challenge for ERAS implementation. These results support the need to uniform ERAS for RC patients and develop strategies to help departments implement ERAS.

Neoadjuvant chemotherapy does not increase peri-operative morbidity following radical cystectomy.

OBJECTIVE: To determine whether use of neoadjuvant chemotherapy (NAC) is associated with a higher risk of post-operative complications following radical cystectomy (RC) for bladder cancer (BCa). MATERIALS AND METHODS: We retrospectively reviewed records of patients undergoing RC for non-metastatic urothelial BCa at 13 tertiary care centres from 2007-2019. Patients who received NAC ('NAC + RC' group) were compared with those who underwent upfront RC ('RC alone' group) for intra-operative variables, incidence of post-operative complications as per the Clavien-Dindo classification (CDC) and rates of re-admission and re-intervention. Multivariable logistic regression analysis was performed to determine predictors of CDC overall and CDC major (grade III-V) complications. We also analysed the trend of NAC utilization over the study period. RESULTS: Of the 3113 patients included, 968 (31.1%) received NAC while the remaining 2145 (68.9%) underwent upfront RC for BCa. There was no significant difference between the NAC + RC and RC alone groups with regards to 30-day CDC overall (53.2% vs 54.6%, p = 0.4) and CDC major (15.5% vs 16.5%, p = 0.6) complications. The two groups were comparable for the rate of surgical re-intervention (14.6% in each group) and re-hospitalization (19.6% in NAC + RC vs 17.9% in RC alone, p = 0.2%) at 90 days. On multivariable regression analysis, NAC use was not found to be a significant predictor of 90-day CDC overall (OR 1.02, CI 0.87-1.19, p = 0.7) and CDC major (OR 1.05, CI 0.87-1.26, p = 0.6) complications. We also observed that the rate of NAC utilization increased significantly (p < 0.001) from 11.1% in 2007 to 41.2% in 2019, reaching a maximum of 48.3% in 2018. CONCLUSION: This large multicentre analysis with a substantial rate of NAC utilization showed that NAC use does not lead to an increased risk of post-operative complications following RC for BCa. This calls for increasing NAC use to allow patients to avail of its proven oncologic benefit.

Carboplatin-based adjuvant chemotherapy versus observation after radical cystectomy in patients with pN1-3 urothelial bladder cancer.

PURPOSE: To test the impact of carboplatin-based ACT on overall survival (OS) in patients with pN1-3 cM0 BCa. METHODS: A retrospective analysis was conducted on 1057 patients with pTany pN1-3 cM0 urothelial BCa treated with or without carboplatin-based ACT after radical cystectomy and bilateral lymph-node dissection between 2002 and 2018 at 12 European and North-American hospitals. No patient received neoadjuvant chemotherapy or radiation therapy. Only patients with negative surgical margins at surgery were included. A 3:1 propensity score matching (PSM) was performed using logistic regression to adjust for baseline characteristics. Univariable and multivariable Cox regression analyses were used to predict the effect of carboplatin-based ACT on OS. The Kaplan-Meier method was used to display OS in the matched cohort. RESULTS: Of the 1057 patients included in the study, 69 (6.5%) received carboplatin-based ACT. After PSM, 244 total patients were identified in two cohorts that did not differ for baseline characteristics. Death was recorded in 114 (46.7%) patients over a median follow-up of 19 months. In the multivariable Cox regression analyses, increasing age at surgery (hazard ratio [HR] 1.02, 95% confidence interval [CI] 1.01-1.06, p < 0.001) and increasing number of positive lymph nodes (HR 1.06, 95% CI 1.01-1.07, p = 0.02) were independent predictors of worse OS. The delivery of carboplatin-based ACT was not predictive of improved OS (HR 0.67, 95% CI 0.43-1.04, p = 0.08). The main limitations of this study are its retrospective design and the relatively low number of patients involved. CONCLUSIONS: Carboplatin-based might not improve OS in patients with pN1-3 cM0 BCa. Our results underline the need for alternative therapies for cisplatin-ineligible patients.

Restaging transurethral resection in ta high-grade nonmuscle invasive bladder cancer: a systematic review.

PURPOSE OF REVIEW: The role of a re-transurethral resection (TUR) is clearly demonstrated in T1 high-grade nonmuscle invasive bladder cancer. However, its role remains controversial for Ta high-risk tumors and the recent European guidelines stated that the second look procedure could be avoided for these patients despite harboring a high-risk of both disease recurrence and progression. We aimed to evaluate the added benefit on staging, response to bacillus Calmette-Guérin and oncological outcomes of re-TUR in patients with Ta high-grade nonmuscle invasive bladder cancer. RECENT FINDINGS: Overall, we identified 15 studies, including 3912 patients from which 743 harbored Ta high-grade disease. Delay between first and second TUR was ranging from 2 to 12 weeks (median 5.6 weeks). The rate of residual disease was 52.8% (range 17-67%). The rate of overall upstaging to T1 and muscle-invasive disease were 10.9 and 4.7%, respectively. Although there was a trend toward improvement of recurrence-free survival outcomes, no definitive conclusions can be drawn due to the retrospective design of the studies included. SUMMARY: Residual tumor is common after initial TUR for Ta high-grade. Re-TUR is useful in reducing the rates of residual disease, may improve staging, response to bacillus Calmette-Guérin and oncological outcomes.

Oncologic Surveillance for Variant Histology Bladder Cancer after Radical Cystectomy.

PURPOSE: Presently, major guidelines do not provide specific recommendations on oncologic surveillance for patients who harbor variant histology (VH) bladder cancer (BCa) at radical cystectomy. We aimed to create a personalized followup scheme that dynamically weighs other cause mortality (OCM) vs the risk of recurrence for VH BCa, and to compare it with a similar one for pure urothelial carcinoma (pUC). MATERIALS AND METHODS: Within a multi-institutional registry, 528 and 1,894 patients with VH BCa and pUC, respectively, were identified. The Weibull regression was used to detect the time points after which the risk of OCM exceeded the risk of recurrence during followup. The risk of OCM over time was stratified based on age and comorbidities, and the risk of recurrence on pathological stage and recurrence site. RESULTS: Individuals with VH had a higher risk of recurrence (recurrence-free survival 30% vs 51% at 10 years, p <0.001) and shorter median time to recurrence (88 vs 123 months, p <0.01) relative to pUC. Among VH, micropapillary variant conferred the greatest risk of recurrence on the abdomen and lungs, and mixed variants carried the greatest risk of metastasizing to bones and other sites compared to pUC. Overall, surveillance should be continued for a longer time for individuals with VH BCa. Notably, patients younger than 60 years with VH and pT0/Ta/T1/N0 at radical cystectomy should continue oncologic surveillance after 10 years vs 6.5 years for pUC individuals. CONCLUSIONS: VH BCa is associated with greater recurrence risk than pUC. A followup scheme that is valid for pUC should not be applied to individuals with VH. Herein, we present a personalized approach for surveillance that may allow an improved shared decision.

The impact of treatment modality on survival in patients with clinical node-positive bladder cancer: results from a multicenter collaboration.

PURPOSE: To assess the impact of perioperative chemotherapy on survival in cN+ BCa patients and analyze it according to the pN status. METHODS: A retrospective analysis was conducted on 639 BCa patients with cTanyN1-3M0 BCa treated with radical cystectomy (RC) and bilateral lymph node dissection (LND) with or without perioperative chemotherapy in ten tertiary referral centers from 1990 to 2017. Selected cN+ patients received induction chemotherapy (IC), whereas adjuvant chemotherapy (ACT) was delivered to selected pN+ patients. Univariable and multivariable Cox regression analyses were used to predict overall mortality (OM) after surgery, adjusting for clinicopathological confounders. Kaplan-Meier analyses assessed OM according to the treatment modality. RESULTS: Overall, 356 (56%) patients were treated with surgery alone, 155 (24%) with IC followed by surgery, and 128 (20%) with ACT following surgery. Over a median follow-up of 25 months, 316 deaths were recorded. At univariable analysis, patients treated with IC and surgery had lower OM both considering cN+ [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.87, p = 0.004] and cN+pN- patients (HR 0.61, 95% CI 0.37-0.99, p = 0.05) compared to those treated with surgery alone. cN+pN+ patients treated with ACT experienced lower OM compared to those treated with IC or surgery alone at multivariable analysis (HR 0.40, 95% CI 0.22-0.74, p = 0.003). CONCLUSION: Patients with cTany cN+ cM0 BCa benefit more in terms of OS when treated with IC followed by RC + LND compared to RC + LND alone, regardless of LNMs at final histopathology examination. More data are needed to assess the role of ACT in the management of cN+ patients.

Adjuvant chemotherapy is ineffective in patients with bladder cancer and variant histology treated with radical cystectomy with curative intent.

OBJECTIVES: Adjuvant chemotherapy (ACT) is recommended for non-organ-confined bladder cancer (BCa) after radical cystectomy (RC) and pelvic lymph node dissection (PLND), but there are sparse data regarding its specific efficacy in patients with histological variants. The aim of our study was to evaluate the role of ACT on survival outcomes in patients with variant histology in a large multicenter cohort. MATERIALS AND METHODS: We retrospectively evaluated data of 3963 patients with BCa treated with RC and bilateral PLND with curative intent at several institutions between 1999 and 2018. The histological type was classified into six groups: pure urothelial carcinoma (PUC) or squamous, sarcomatoid, micropapillary, glandular and neuroendocrine differentiation. Multivariable competing risk analysis was applied to assess the role of ACT on recurrence and cancer-specific mortality (CSM) in each histological subtype. RESULTS: Of the 3963 patients included in the study, 23% had variant histology at RC specimen and 723 (18%) patients received ACT. ACT was found to be significantly associated with reduced risk of recurrence (sub-hazard ratio [SHR]: 0.55, confidence interval [CI] 0.42-0.71, p < 0.001) and CSM (SHR: 0.58, CI 0.44-0.78, p < 0.001) in the PUC only, while no histological subtype received a significant benefit on survival outcomes (all p > 0.05) from administration of ACT. The limitation of the study includes the retrospective design, the lack of a central pathology review and the number of ACT cycles. CONCLUSION: In our study, the administration of ACT was associated with improved survival outcomes in PUC only. No histological subtype found a benefit in overall recurrence and CSM from ACT.

Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes.

PURPOSE: This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette-Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). MATERIALS AND METHODS: Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo's approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. RESULTS: The median TTBCG was 95 days (interquartile range (IQR): 71-127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. CONCLUSION: This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression.

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

OBJECTIVES: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. PATIENTS AND METHODS: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG ≥ 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. RESULTS: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%). CONCLUSION: The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.

Neutrophil, Platelets, and Eosinophil to Lymphocyte Ratios Predict Gleason Score Upgrading in Low-Risk Prostate Cancer Patients.

BACKGROUND: Several biochemical and clinical markers have been proposed for selecting patients for active surveillance (AS). However, some of these are expensive and not easily accessible. Moreover, currently about 30% of patients on AS harbor aggressive disease. Hence, there is an urgent need for other tools to accurately identify patients with low-risk prostate cancer (PCa). PATIENTS: We retrospectively reviewed the medical records of 260 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 (GS) ≤6 grade, and prostate-specific antigen density < 0.2 ng/mL/cc. METHODS: Univariate and multivariate analyses were performed to evaluate the association of patient and tumor characteristics with reclassification, defined as upstaged (pathological stage >pT2) and upgraded (GS ≥7) disease. A base model (age, prostate-specific antigen, prostate volume, and clinical stage) was compared with models considering neutrophil to lymphocyte ratio (NLR) or platelets to lymphocyte ratio (PLR), monocyte to lymphocyte (MLR), and eosinophil to lymphocyte ratio (ELR). OR and 95% CI were calculated. Finally, a decision curve analysis was performed. RESULTS: Univariate and multivariate analyses showed that NLR, PLR, and ELR upgrading were significantly associated with upgrading (ORs ranging from 2.13 to 4.13), but not with upstaging except for MLR in multivariate analysis, showing a protective effect. CONCLUSION: Our results showed that NLR, PLR, and ELR are predictors of Gleason upgrading. Therefore, these inexpensive and easily available tests might be useful in the assessment of low-risk PCa, when considering patients for AS.

Robot assisted radical prostatectomy in kidney transplant recipients: surgical, oncological and functional outcomes of two different robotic approaches.

BACKGROUND: To date, few series on robot-assisted radical prostatectomy (RARP) in kidney transplant recipients (KTRs) have been published. PURPOSE: To report the experience of two referral centers adopting two different RARP approaches in KTRs. Surgical, oncological and functional results were primary outcomes evaluated in the study. MATERIAL AND METHODS: We retrospectively analyzed data from 9 KTRs who underwent transperitoneal RARP or Retzius-sparing RARP for PCa from October 2012 to April 2016. Data were reported as median and interquartile range (IQR). Pre- and postoperative outcomes were compared by non-parametric Wilcoxon signed-rank test. Significant differences were accepted when p ≤ 0.05. Overall survival was assessed using Kaplan-Meier method. RESULTS: Four KTRs underwent a T-RARP and 5 a RS-RARP. Patient median age was 60 (56-63) years. Charlson comorbidity index was 6 (5-6). Preoperative median PSA was 5.6 (5-15) ng / mL. Preoperative Gleason score (GS) was 6 in 5 patients, 7 (3 + 4) in 3, and 8 (4 + 4) in one. Pre- and postoperative creatinine were 1.17 (1.1; 1.4) and 1.3 (1.07; 1.57) mg / dL (p = 0.237), while eGFR was 66 (60-82) and 62 (54-81) mL / min / 1.73m2 (p = 0.553), respectively. One (11.1%) Clavien-Dindo grade II complication occurred. Two extended template lymphadenectomies were performed, both with nodal invasion. These two patients experienced a biochemical recurrence and were subjected to RT. Two patients (22.2%) had PSMs. Median follow-up was 42 months. Seven patients (77.8%) were continent, 5 (55.6%) were potent. Two (22.2%) patients died during follow-up for oncologic unrelated causes. CONCLUSIONS: Our series suggests that both RARP approaches are safe and feasible techniques in KTRs for PCa.

Thulium-yttrium-aluminium-garnet (Tm:YAG) laser treatment of penile cancer: oncological results, functional outcomes, and quality of life.

PURPOSE: To evaluate the oncological and functional outcomes of patients diagnosed with penile cancer undergoing conservative treatment through thulium-yttrium-aluminium-garnet (Tm:YAG) laser ablation. METHODS: Twenty-six patients with a penile lesion underwent ablation with a RevoLix 200 W continuous-wave laser. The procedure was carried out with a pen-like laser hand piece, using a 360 µm laser fiber and 15-20 W of power. Median (IQR) follow-up time was 24 (15-30) months. Recurrence rate and post-operative sexual function were assessed. RESULTS: Median age at surgery was 61 years. Median (inter quartile range) size of the lesions was 15 [10-20] mm. Overall, 11 (47.8%) and 12 (52.2%) at the final pathology presented in situ and invasive squamous cell carcinoma (SCC), respectively. The final pathological stage was pTis, pT1a, pT2, and pT3 in 11 (47.8%), 7 (30.4%), 3 (13.0%), and 2 (8.7%) patients, respectively. Moreover, four (17.4%) patients had a recurrence of which three (13.0%) and one (4.3%) patients developed an invasive or in situ recurrence, respectively. After treatment 6 (26.1%) patients reported a conserved penile sensitivity, while 13 (56.5%) and 4 (17.4%) patients experienced a better or worse sensitivity after ablation, respectively. Post-treatment sexual activity was achieved within the first month after laser ablation in 82.6% of the patients. CONCLUSION: Early stage penile carcinomas can be effectively treated with an organ preservation strategy. Tm:YAG conservative laser treatment is easy, safe and offers good functional outcome, with a minor impact on patient's quality of life.

Multiparametric Magnetic-Resonance to Confirm Eligibility to an Active Surveillance Program for Low-Risk Prostate Cancer: Intermediate Time Results of a Third Referral High Volume Centre Active Surveillance Protocol.

BACKGROUND: To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification. MATERIALS: From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP. RESULTS: PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively. CONCLUSIONS: MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions.

Short-Form Charlson Comorbidity Index for Assessment of Perioperative Mortality After Radical Cystectomy.

Background: The Deyo adaptation of the Charlson comorbidity index (DaCCI), which relies on 17 comorbid condition groupings, represents one of the most frequently used baseline comorbidity assessment tools in retrospective database studies. However, this index is not specific for patients with bladder cancer (BCa) treated with radical cystectomy (RC). The goal of this study was to develop a short-form of the original DaCCI (DaCCI-SF) that may specifically predict 90-day mortality after RC, with equal or better accuracy. Patients and Methods: Between 2000 and 2009, we identified 7,076 patients in the SEER-Medicare database with stage T1 through T4 nonmetastatic BCa treated with RC. We randomly divided the population into development (n=6,076) and validation (n=1,000) cohorts. Within the development cohort, logistic regression models tested the ability to predict 90-day mortality with various iterations of the DaCCI-SF, wherein <17 original comorbid condition groupings were included after adjusting for age, sex, race, T stage, and N stage. We relied on the Akaike information criterion to identify the most parsimonious and informative set of comorbid condition groupings. Accuracy of the DaCCI and the DaCCI-SF was tested in the external validation cohort. Results: Within the development cohort, the most parsimonious and informative model resulted in the inclusion of 3 of the 17 (17.6%) original comorbid condition groupings: congestive heart failure, cerebrovascular disease, and chronic pulmonary disease. Within the validation cohort, the accuracy was 68.4% for the DaCCI versus 69.7% for the DaCCI-SF. Higher accuracy of the DaCCI-SF was confirmed in subgroup analyses performed according to age (≤75 vs >75 years), stage (organ-confined vs non-organ-confined), type of diversion (ileal-conduit vs non-ileal-conduit), and treatment period. Conclusions: DaCCI-SF relies on 17.6% of the original comorbid condition groupings and provides higher accuracy for predicting 90-day mortality after RC compared with the original DaCCI, especially in most contemporary patients.

A nomogram predicting the cancer-specific mortality in patients eligible for radical cystectomy evaluating clinical data and neoadjuvant cisplatinum-based chemotherapy.

PURPOSE: Despite the increasing number of studies confirming the importance of neoadjuvant chemotherapy (NC) in patients before radical cystectomy (RC) for bladder cancer (BCa), NC remains underused. The aim of our study was to develop a nomogram predicting the cancer-specific mortality (CSM) of patients who underwent RC for transitional BCa, evaluating the available clinical information and the NC. MATERIALS AND METHODS: We identified 423 patients who underwent RC and pelvic lymph node dissection, treated or not with NC, in two European high-volume centers between 2007 and 2013. Chi-square and Student's t tests were used to evaluate differences between groups. Kaplan-Meier curves were used to assess time to cancer-specific (CSS) and overall survival (OS). Uni- (UVA) and multivariable (MVA) Cox regression analyses were developed to address predictors of CSS and OS. A nomogram based on the Cox regression coefficient was developed to show the impact of NC on CSM. RESULTS: Mean follow-up was 20.3 months. Our population had mainly pT2 disease (77.1%), and 19.4% had preoperative cisplatinum-based NC. NC showed better CSS at UVA (p = 0.014) and MVA (odds ratio: 0.44; p = 0.043). Overall, the 3-year OS and the CSS rate were 69.3 and 79%, respectively. The nomogram developed to predict the 36-month CSM showed predictive accuracy of 67%. CONCLUSIONS: We developed the first nomogram predicting the 36-month CSM rate in patients with high-risk BCa according to the clinical data. Moreover, we demonstrate that preoperative cisplatinum-based chemotherapy is associated with better CSS.

Evolution from laparoscopic to robotic nephron sparing surgery: a high-volume laparoscopic center experience on achieving 'trifecta' outcomes.

OBJECTIVE: To evaluate the transition from laparoscopic (LPN) to robotic partial nephrectomy (RPN) in our institution using 'trifecta' outcomes as surrogate marker of efficacy. PATIENTS AND METHODS: We identified 347 patients (LPN = 303, RPN = 44) in our prospectively maintained PN database between 2000 and 2014. The patients were chronologically divided into G1-first 151 LPN cases, G2-subsequent 152 LPN cases and G3-all RPN patients. Trifecta outcomes were defined as warm ischemia time (WIT) ≤25 min, no positive surgical margin (PSM) and complications ≤Clavien 2. Multivariable logistic model was used to analyze the predictors of the trifecta outcomes. RESULTS: The tumor complexity significantly increased from G1 to G3. We achieved lower WIT and less high-grade complication (Clavien ≥ 3) from G1 to G2, and the trend continued even with transition to RPN. PSM was consistently low throughout the transition. Renal functional outcomes always showed a significant positive trend, and with RPN, we achieved improved recovery of renal function (44 vs 57 vs 82 %, p < 0.05). The overall 'trifecta' rates increased significantly from G1 to G2 and reached 81.8 % in RPN (48 vs 75.6 vs 81 %, p < 0.01). Multivariate analysis has shown that the use of robot has significant effect on achieving overall trifecta. The limitations of the study are being retrospective and non-randomized, and the trifecta definitions were not externally validated. CONCLUSIONS: Our transition to RPN was essentially a continuation of our previous LPN experience as we continue to achieve higher 'trifecta' rates inspite of increasing tumor complexity.