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Background Salvage treatment for local recurrence after prior partial nephrectomy (PN) or local tumor ablation (LTA) for kidney cancer is, as of yet, poorly investigated. Objective To classify the treatments and standardize the nomenclature of salvage robot-assisted renal surgery, to describe the surgical technique for each scenario, and to investigate complications, renal function, and oncologic outcomes. Design, setting, and participants Sixty-seven patients underwent salvage robot-assisted renal surgery from October 2010 to December 2020 at nine tertiary referral centers. Surgical procedure Salvage robot-assisted renal surgery classified according to treatment type as salvage robot-assisted partial or radical nephrectomy (sRAPN or sRARN) and according to previous primary treatment (PN or LTA). Measurements Postoperative complications, renal function, and oncologic outcomes were assessed. Results and limitations A total of 32 and 35 patients underwent salvage robotic surgery following PN and LTA, respectively. After prior PN, two patients underwent sRAPN, while ten underwent sRARN for a metachronous recurrence in the same kidney. No intra- or perioperative complication occurred. For local recurrence in the resection bed, six patients underwent sRAPN, while 14 underwent sRARN. For sRAPN, the intraoperative complication rate was 33%; there was no postoperative complication. For sRARN, there was no intraoperative complication and the postoperative complication rate was 7%. At 3 yr, the local recurrence-free rates were 64% and 82% for sRAPN and sRARN, respectively, while the 3-yr metastasis-free rates were 80% and 79%, respectively. At 33 mo, the median estimated glomerular filtration rates (eGFRs) were 57 and 45 ml/min/1.73 m2 for sRAPN and sRARN, respectively. After prior LTA, 35 patients underwent sRAPN and no patient underwent sRARN. There was no intraoperative complication; the overall postoperative complications rate was 20%. No local recurrence occurred. The 3-yr metastasis-free rate was 90%. At 43 mo, the median eGFR was 38 ml/min/1.73 m2. The main limitations are the relatively small population and the noncomparative design of the study. Conclusions Salvage robot-assisted surgery has a safe complication profile in the hands of experienced surgeons at high-volume institutions, but the risk of local recurrence in this setting is non-negligible. Patient summary Patients with local recurrence after partial nephrectomy or local tumor ablation should be aware that further treatment with robot-assisted surgery is not associated with a worrisome complication profile, but also that they are at risk of further recurrence.

The rising costs of cancer care with the introduction of new agents are a challenge. The impact of these costs differs among countries. We compare costs for metastatic prostate cancer, with prices normalized to international dollars, as an example that highlights the need for cost-effectiveness analyses in trials and treatment guidelines.

Background: Infertile men are at greater risk for oncological and nononcological chronic disease than fertile individuals. Objective: To investigate prostate-specific antigen (PSA) values in men presenting for primary couple's infertility compared with a cohort of fertile individuals, according to the recommendation of the European Association of Urology guidelines that a first PSA assessment should be done at 40–45 yr of age. Design, setting, and participants: This is a cross-sectional study. Data from 956 (90%) infertile men and 102 (9.6%) fertile participants were analysed. Circulating hormones, total PSA, and semen parameters were investigated in every man. Outcome measurements and statistical analysis: Descriptive statistics, local polynomial smoothing, and linear regression models were used to test potential associations with PSA levels. Results and limitations: Overall, PSA >1 ng/ml was found in 318 (30%) men. Serum PSA was higher (p = 0.02), while serum testosterone (p < 0.01) was lower in infertile than in fertile men. In participants younger than 40 yr, 176 (27%) men had PSA >1 ng/ml; of them, a greater proportion were infertile (28% infertile vs 17% fertile, p = 0.03). At multivariable linear regression analysis, infertile status (coefficient 0.21; 95% confidence interval 0.02–0.39) was associated with higher PSA values, after adjusting for age and serum testosterone level. This was a single-centre study, raising the possibility of selection biases. Conclusions: Infertile men have higher PSA values than fertile individuals. Of all, almost one out of three primary infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Patient summary: In this study, we observed that (1) infertile men have higher prostate-specific antigen (PSA) values than fertile individuals and (2) a greater proportion of infertile men younger than 40 yr had total PSA >1 ng/ml at the first assessment. These data might be relevant to study the potential clinical impact of more rigorous screening in primary infertile men. Infertile men have higher prostate-specific antigen (PSA) values than fertile individuals. One out of three infertile men younger than 40 yr has a first total PSA value of >1 ng/ml. Serum PSA is related to worse semen quality in infertile men.

Background: Extended pelvic nodal dissection (ePLND) represents the gold standard for nodal staging in prostate cancer (PCa). Prostate-specific membrane antigen (PSMA) radioguided surgery (RGS) could identify lymph node invasion (LNI) during robotassisted radical prostatectomy (RARP).Objective: To report the planned interim analyses of a phase 2 prospective study (NCT04832958) aimed at describing PSMA-RGS during RARP.Design, setting, and participants: A phase 2 trial aimed at enrolling 100 patients with intermediate- or high-risk cN0cM0 PCa at conventional imaging with a risk of LNI of >5% was conducted. Overall, 18 patients were enrolled between June 2021 and March 2022. Among them, 12 patients underwent PSMA-RGS and represented the study cohort.Surgical procedure: All patients received Ga-68-PSMA positron emission tomography (PET)/magnetic resonance imaging; Tc-99m-PSMA-I&S was synthesised and administered intravenously the day before surgery, followed by single-photon emission computed tomography/computed tomography. A Drop-In gamma probe was used for in vivo measurements. All positive lesions (count rate >= 2 compared with background) were excised and ePLND was performed.Measurements: Side effects, perioperative outcomes, and performance characteristics of robot-assisted PSMA-RGS for LNI were measured.Results and limitations: Overall, four (33%), six (50%), and two (17%) patients had intermediate-risk, high-risk, and locally advanced PCa. Overall, two (17%) patients had pathologic nodal uptake at PSMA PET. The median operative time, blood loss, and length of stay were 230 min, 100 ml, and 5 d, respectively. No adverse events and intraoperative complications were recorded. One patient experienced a 30-d complication (ClavienDindo 2; 8.3%). Overall, three (25%) patients had LNI at ePLND. At per-region analyses on 96 nodal areas, sensitivity, specificity, positive predictive value, and negative predictive value of PSMA-RGS were 63%, 99%, 83%, and 96%, respectively. On a per-patient level, sensitivity, specificity, positive predictive value, and negative predictive values of PSMA-RGS were 67%, 100%, 100%, and 90%, respectively.Conclusions: Robot-assisted PSMA-RGS in primary staging is a safe and feasible procedure characterised by acceptable specificity but suboptimal sensitivity, missing micrometastatic nodal disease.Patient summary: Prostate-specific membrane antigen radioguided robot-assisted surgery is a safe and feasible procedure for the intraoperative identification of nodal metastases in cN0cM0 prostate cancer patients undergoing robot-assisted radical prostatectomy with extended pelvic lymph node dissection. However, this approach might still miss micrometastatic nodal dissemination. (c) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.

Background Over the years, several techniques for performing robot-assisted prostatectomy have been implemented in an effort to achieve optimal oncological and functional outcomes. Objective To provide an evidence-based description and video-based illustration of currently available dissection techniques for robotic prostatectomy. Design, setting, and participants A literature search was performed to retrieve articles describing different surgical approaches and techniques for robot-assisted radical prostatectomy (RARP) and to analyze data supporting their use. Video material was provided by experts in the field to illustrate these approaches and techniques. Surgical procedure Multiple surgical approaches are available: extraperitoneal, transvesical, transperitoneal posterior, transperitoneal anterior, Retzius sparing, and transperineal. Surgical techniques for prostatic dissection sensu strictu are the following: omission of the endopelvic fascia dissection, bladder neck preservation, incremental nerve sparing by means of an antegrade or retrograde approach, and preservation of the puboprostatic ligaments and dorsal venous complex. Recently, techniques for total or partial prostatectomy have been described. Measurements Different surgical approaches and techniques for robotic prostatectomy have been analyzed. Results and limitations Two randomized controlled trials evaluating the extraperitoneal versus the transperitoneal approach have demonstrated similar results. Level I evidence on the Retzius-sparing approach demonstrated earlier return to continence than the traditional anterior approach. The question whether Retzius-sparing RARP is associated with a higher rate of positive surgical margins is still open due to the intrinsic bias in terms of surgical expertise in the available comparative studies. This technique also offers an advantage in patients who have received kidney transplantation. Retrospective evidence suggests that the more the anatomical dissection (eg., more periprostatic tissue is preserved), the better the functional outcome in terms of continence. Yet, two randomized controlled trials evaluating the different techniques of dissection have so far been produced. Partial prostatectomies should not be offered outside clinical trials. Conclusions Several techniques and approaches are available for prostate dissection during RARP. While the Retzius-sparing approach seems to provide earlier return to continence than the traditional anterior transperitoneal approach, no technique has been proved to be superior to other(s) in terms of long-term outcomes in randomized studies. Patient summary We have summarized available approaches for the surgical treatment of prostate cancer. Specifically, we described the different techniques that can be adopted for the surgical removal of the prostate using robotic technology.

Focal therapy (FT) for prostate cancer (PCa) is emerging as a novel therapeutic approach for patients with low- to intermediate-risk disease, in order to provide acceptable oncological control, whilst avoiding the side effects of radical treatment. Evidence regarding the ideal follow-up strategy and the significance of prostate-specific antigen (PSA) kinetics after treatment is needed. In this study, we aimed to assess the value of the percentage of PSA reduction (%PSA reduction) after FT in predicting the likelihood of any additional treatment or any radical treatment. We retrospectively analysed a multicentre cohort of 703 men receiving FT for low- and intermediate-risk PCa. Overall, the rates of any additional treatment and any radical treatment were 30% and 13%, respectively. The median follow-up period was 41 mo. The median %PSA reduction after FT was 73%. At Cox multivariable analysis, %PSA reduction was an independent predictor of any additional treatment (hazard ratio [HR]: 0.96; p 90%, the probability of any additional treatment within 5 yr was 20%. Conversely, for %PSA reduction of

Background: In the PURE-01 study, pembrolizumab was given preoperatively before radical cystectomy in clinical T2-4aN0M0 patients. An accurate clinical response assessment may be useful for developing new perioperative strategies in these patients. Objective: To evaluate the association between bladder multiparametric magnetic resonance imaging (mpMRI) findings after pembrolizumab and the pathological complete response (CR; pT0). Design, setting, and participants: Patients were staged using bladder mpMRI whereby radiologists were asked to characterize the following parameters: residual disease at T1- and T2-weighted images (step 1: yes/no), presence of hyperintense spots within the bladder wall on diffusion-weighted imaging (step 2: yes/no), and presence of pathological contrast enhancement (step 3: yes/no), before and after three cycles of pembrolizumab. Examinations were internally assessed by two senior radiologists and externally evaluated by a third senior radiologist. Intervention: To evaluate bladder tumor response after neoadjuvant pembrolizumab, mpMRI was used. Outcome measurements and statistical analysis: The primary objective was to predict the pT0 after neoadjuvant pembrolizumab by relying on the mpMRI findings. Cohen's kappa statistics was used to assess interobserver variability. Univariable analyses for pT0 were performed including internal and external post-therapy mpMRI steps. Results and limitations: From February 2017 to October 2018, 82 patients (164 total mpMRI assessments) were analyzed. The agreement between the internal and external mpMRI assessments after therapy was acceptable (κ values ranging from 0.5 to 0.76). Each mpMRI step was significantly associated with pT0 in both internal and external assessments. In patients with CR/no evidence of residual disease (NED) in all internally evaluated mpMRI steps (N = 37), the pT0 was seen in 23 (62%), compared with 19 of 26 externally evaluated NED patients (73%). Conclusions: In post-pembrolizumab muscle-invasive bladder cancer, mpMRI sequence assessment had acceptable interobserver variability and represented the basis for the proposal of a radiological CR/NED status definition predicting the pT0 response to pembrolizumab. After validation of these findings with external datasets, we propose this tool for developing bladder-sparing immunotherapy maintenance therapies. Patient summary: Assessment of the extent of disease in patients with muscle-invasive bladder cancer using conventional imaging yields serious limitations. In the PURE-01 study, we evaluated the potential of bladder multiparametric magnetic resonance imaging (MRI) to predict the pathological complete response to neoadjuvant pembrolizumab. After validation with larger datasets, the proposed stepwise assessment incorporating multiparametric MRI sequences will be used at our center to develop bladder-sparing approaches in future studies. • In the PURE-01 study, multiparametric magnetic resonance imaging (mpMRI) of the bladder was used to stage and evaluate the response to pembrolizumab, before radical cystectomy. • Assessments of mpMRI sequence were externally reviewed, showing preliminary but promising reproducibility. • We proposed an mpMRI-based definition of complete response predicting the pathological complete response to pembrolizumab that was externally replicated.

Background Patients with predominant variant histology (VH) of bladder tumors, defined as involving >50 % of the tumor specimens, are typically excluded from clinical trials, and for these patients, the efficacy of standard chemotherapy is limited. Objective To evaluate the activity of preoperative pembrolizumab in patients with muscle-invasive bladder carcinoma (MIBC) and VH, enrolled in PURE-01 study (NCT02736266). Design, setting, and participants In the open-label, single-arm, phase 2 PURE-01 study, three courses of 200 mg pembrolizumab preceding radical cystectomy (RC) were administered in T2-4aN0M0 MIBC patients. The amended study design included patients with predominant VH. Intervention Neoadjuvant pembrolizumab and RC. Outcome measurements and statistical analysis Pathological complete response (pT0) in intention-to-treat population was the primary endpoint. Biomarker analyses included programmed cell-death ligand-1 (PD-L1) expression using the combined positive score (CPS; Dako 22C3 antibody) and comprehensive genomic profiling (FoundationOne assay). Multivariable logistic regression analyses (MVAs) evaluated the histological category (predominant VH vs nonpredominant VH vs pure urothelial carcinoma), tumor mutational burden (TMB) and CPS in association with the pathological response. Results and limitations From February 2017 to June 2019, 114 patients were enrolled; 34 (30%) of them presented with VH, including 19 (17%) with predominant VH. In total, the pT0 rate was 37% (95% confidence interval [CI]: 28–46) and the pT ≤ 1 rate was 55% (95% CI: 46–65). The majority of predominant VH patients presented with squamous-cell carcinoma (SCC; N = 7), and six of seven (86%) had downstaging to pT ≤ 1, with one pT0; two of three lymphoepithelioma-like (LEL) variants had a pT0 response. None of the remaining nine predominant VHs had a response. On MVA, TMB and CPS were associated with both the pT0 and the pT ≤ 1 response, regardless of tumor histology. Conclusions The updated PURE-01 results confirm the activity of neoadjuvant pembrolizumab in MIBC. Patients with SCC and LEL features may be suitable for neoadjuvant immunotherapy trials. CPS and TMB are the key response predictors irrespective of the histological subtypes. Patient summary In the PURE-01 study, we have preliminarily evaluated the activity of neoadjuvant pembrolizumab in patients with predominant variant histology (VH). Of these patients, those harboring squamous-cell carcinoma or a lymphoepithelioma-like variant feature had major, although preliminary, pathological responses compared with those with other predominant VHs. Expression of programmed cell-death ligand-1 and tumor mutational burden may predict the pathological response to pembrolizumab, and provide a rationale for selecting patients according to these features instead of the histological bladder cancer subtypes.

Background: The PURE-01 study (NCT02736266) evaluated the use of pembrolizumab before radical cystectomy (RC) in muscle-invasive bladder cancer (MIBC). Objective: To evaluate the ability of molecular signatures to predict the pathological complete response (CR: ypT0N0) and progression-free survival (PFS) after pembrolizumab and RC. Design, setting, and participants: We analyzed the expression data from patients with T2–4aN0M0 MIBC enrolled in the PURE-01 study (N = 84) and from patients of a retrospective multicenter cohort treated with cisplatin-based neoadjuvant chemotherapy (NAC; N = 140). Intervention: Neoadjuvant pembrolizumab or NAC and RC. Outcome measurements and statistical analysis: Immune signatures and molecular subtyping (The Cancer Genome Atlas, consensus model, and genomic subtyping classifier [GSC]) were evaluated in relation to CR and PFS. Multivariable logistic regression analyses for CR were used, adjusting for gender and clinical T stage. Results and limitations: The Immune190 signature was significant for CR on multivariable logistic regression analyses (p = 0.02) in PURE-01, but not in the NAC cohort (p = 0.7). Hallmark signatures for interferon gamma (IFNγ; p = 0.004) and IFNα response (p = 0.006) were also associated with CR for PURE-01, but not for NAC (IFNγ: p = 0.9 and IFNα: p = 0.8). In PURE-01, 93% of patients with the highest Immune190 scores (>1st quartile) had 2-yr PFS versus 79% of those with lower scores; no difference was observed in NAC patients, as well as for the other hallmarks in both groups. The neuroendocrine-like subtype had the worst 2-yr PFS in all three subtyping models (33%) and the GSC claudin-low subtype had the best, with no recurrences in 2 yr. Basal subtypes (across classifications) with higher Immune190 scores showed 100% 2-yr PFS after pembrolizumab therapy (p = 0.04, compared with basal-Immune190 low). Statistical analyses are limited by the small number of events and short follow-up. Conclusions: Higher RNA-based immune signature scores were significantly associated with CR and numerically improved PFS outcomes after pembrolizumab, but not after NAC. These data emphasize that RNA profiling is a potential tool for personalizing neoadjuvant therapy selection. Patient summary: We used gene expression profiling to evaluate the association between immune gene expression and response to neoadjuvant immunotherapy, compared with standard chemotherapy, in patients with muscle-invasive bladder cancer (MIBC). We found a significant association between immune gene expression and response to pembrolizumab, but not chemotherapy. We conclude that gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC. By using gene expression profiling of transurethral bladder tumor resection samples from patients with muscle-invasive bladder cancer (MIBC), we reported a significant association between pre-existing immune gene expression and response to neoadjuvant pembrolizumab, but not to neoadjuvant chemotherapy. Different outcomes were also obtained according to the molecular subtype. Gene expression profiling has the potential to guide personalized neoadjuvant therapy in MIBC.

The risk of high-grade prostate cancer, given a family history of cancer, has been described in the general population, but not among men selected for prostate biopsy in an international cohort.To estimate the risk of high-grade prostate cancer on biopsy based on a family history of cancer.This is a multicenter study of men undergoing prostate biopsy from 2006 to 2019, including 12 sites in North America and Europe. All sites recorded first-degree prostate cancer family histories; four included more detailed data on the number of affected relatives, second-degree relatives with prostate cancer, and breast cancer family history.Multivariable logistic regressions evaluated odds of high-grade (Gleason grade group ≥2) prostate cancer. Separate models were fit for family history definitions, including first- and second-degree prostate cancer and breast cancer family histories.A first-degree prostate cancer family history was available for 15 799 men, with a more detailed family history for 4617 (median age 65 yr, both cohorts). Adjusted odds of high-grade prostate cancer were 1.77 times greater (95% confidence interval [CI] 1.57-2.00, p0.001, risk ratio [RR] = 1.40) with first-degree prostate cancer, 1.38 (95% CI 1.07-1.77, p = 0.011, RR = 1.22) for second-degree prostate cancer, and 1.30 (95% CI 1.01-1.67, p = 0.040, RR = 1.18) for first-degree breast cancer family histories. Interaction terms revealed that the effect of a family history did not differ based on prostate-specific antigen but differed based on age. This study is limited by missing data on race and prior negative biopsy.Men with indications for biopsy and a family history of prostate or breast cancer can be counseled that they have a moderately increased risk of high-grade prostate cancer, independent of other risk factors.In a large international series of men selected for prostate biopsy, finding a high-grade prostate cancer was more likely in men with a family history of prostate or breast cancer.

Prostate cancer (PCa) is one of the first three causes of cancer mortality in Europe. Screening in asymptomatic men (aged 55–69 yr) using prostate-specific antigen (PSA) is associated with a migration toward lower staged disease and a reduction in cancer-specific mortality. By 20 yr after testing, around 100 men need to be screened to prevent one PCa death. While this ratio is smaller than for breast and colon cancer, the long natural history of PCa means many men die from other causes. As such, the nonselective use of PSA testing and radical treatments can lead to overdiagnosis and overtreatment. The European Association of Urology (EAU) supports measures to encourage appropriate PCa detection through PSA testing, while reducing overdiagnosis and overtreatment. These goals may be achieved using personalized risk-stratified approaches. For diagnosis, the greatest benefit from early detection is likely to come in men assessed using baseline PSA levels at the age of 45 yr to individualize screening intervals. Multiparametric magnetic resonance imaging as well as risk calculators based on family history, ethnicity, digital rectal examination, and prostate volume should be considered to triage the need for biopsy, thus reducing the risk of overdiagnosis. For treatment, the EAU advocates balancing patient's life expectancy and cancer's mortality risk when deciding an approach. Active surveillance is encouraged in well-informed patients with low-risk and some intermediate-risk cancers, as it decreases the risks of overtreatment without compromising oncological outcomes. Conversely, the EAU advocates radical treatment in suitable men with more aggressive PCa. Multimodal treatment should be considered in locally advanced or high-grade cancers. Patient summary: Implementation of prostate-specific antigen (PSA)-based screening should be considered at a population level. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45 yr). The level of this test, combined with family history, ethnicity, and other factors, can be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated. The European Association of Urology supports the implementation of prostate-specific antigen (PSA)-based screening at a population level in Europe. Men at risk of prostate cancer should have a baseline PSA blood test (eg, at 45 yr). This, together with family history, ethnicity, and other factors, should be used to determine subsequent follow-up. Magnetic resonance imaging scans and novel biomarkers should be used to determine which men need biopsy and how any cancers should be treated.

Background Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies. Objective To assess the accuracy of available tools to predict LNI and to develop a novel model for men diagnosed via MRI-targeted biopsies. Design, setting, and participants A total of 497 patients diagnosed via MRI-targeted biopsies and treated with RP and extended pelvic lymph node dissection (ePLND) at five institutions were retrospectively identified. Outcome measurements and statistical analyses Three available models predicting LNI were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analyses. A nomogram predicting LNI was developed and internally validated. Results and limitations Overall, 62 patients (12.5%) had LNI. The median number of nodes removed was 15. The AUC for the Briganti 2012, Briganti 2017, and MSKCC nomograms was 82%, 82%, and 81%, respectively, and their calibration characteristics were suboptimal. A model including PSA, clinical stage and maximum diameter of the index lesion on multiparametric MRI (mpMRI), grade group on targeted biopsy, and the presence of clinically significant PCa on concomitant systematic biopsy had an AUC of 86% and represented the basis for a coefficient-based nomogram. This tool exhibited a higher AUC and higher net benefit compared to available models developed using standard biopsies. Using a cutoff of 7%, 244 ePLNDs (57%) would be spared and a lower number of LNIs would be missed compared to available nomograms (1.6% vs 4.6% vs 4.5% vs 4.2% for the new nomogram vs Briganti 2012 vs Briganti 2017 vs MSKCC). Conclusions Available models predicting LNI are characterized by suboptimal accuracy and clinical net benefit for patients diagnosed via MRI-targeted biopsies. A novel nomogram including mpMRI and MRI-targeted biopsy data should be used to identify candidates for ePLND in this setting. Patient summary We developed the first nomogram to predict lymph node invasion (LNI) in prostate cancer patients diagnosed via magnetic resonance imaging-targeted biopsy undergoing radical prostatectomy. Adoption of this model to identify candidates for extended pelvic lymph node dissection could avoid up to 60% of these procedures at the cost of missing only 1.6% patients with LNI.

Robot-assisted partial nephrectomy (RAPN) outcomes might be importantly affected by increasing surgical experience (EXP). The aim of the study is to investigate the effect of EXP on warm ischemia time (WIT), presence of at least one Clavien-Dindo ≥2 postoperative complication (CD ≥ 2), and positive surgical margins (PSMs) to define the learning curve for RAPN. We evaluated 457 consecutive patients diagnosed with a cT1-T2 renal mass were evaluated. EXP was defined as the total number of RAPNs performed by each surgeon before each patient's operation. Median WIT was 14min and the rate of CD ≥ 2 and PSMs was 15% and 4%, respectively. At multivariable regression analyses adjusted for case mix, EXP resulted associated with shorter WIT (p

Cytoreductive radical prostatectomy (CRP) may offer a survival advantage, according to several retrospective analyses. However, few data are available regarding the morbidity of radical prostatectomy in the metastatic setting. We addressed intra- and postoperative complications of CRP relative to radical prostatectomy for nonmetastatic prostate cancer (nmRP). Within the National Inpatient Sample database (2008–2013), we identified patients who underwent CRP versus nmRP. Propensity score matching to reduce the effect of inherent differences between CRP and nmRP patients, multivariable logistic regression models, Poisson regression models, and linear regression models were used. Of 76 378 patients, 1.2% (n = 953) underwent CRP. CRP resulted in higher rates of overall (odds ratio [OR]: 1.34, p = 0.01), intraoperative (OR: 2.61, p = 0.005), and miscellaneous surgical complications (OR: 1.69, p = 0.02). Moreover, CRP was associated with longer stay (OR: 1.07, p = 0.01) and higher total hospital charges ($810 more per surgery, p = 0.0004). Intra- and postoperative complications associated with CRP are higher than those of nmRP. Similarly, an increase in total hospital charges is associated with CRP. Nonetheless, CRP complication profile validates its safety and feasibility. Patient summary: In this population-based study, we recorded higher intra- and postoperative complications rates for CRP versus nmRP. Nonetheless, CRP complication rates appear manageable but require explicit discussion at counseling. Perioperative complications associated with cytoreductive radical prostatectomy are moderately higher than those of radical prostatectomy in nonmetastatic prostate cancer patients. Similarly, total hospital charges are marginally higher. Nonetheless, the complication profile of cytoreductive radical prostatectomy validates its safety and feasibility in highly selected patients.

In locally advanced and metastatic malignancies, antibiotic (ATB) therapy has a negative effect on immunotherapy efficacy. Therefore, we aimed to evaluate whether ATB therapy and use of specific ATB classes with concomitant neoadjuvant pembrolizumab affected pathologic complete response (ypT0N0) and relapse-free survival (RFS) for patients with clinical T2–4N0M0 bladder cancer enrolled in the PURE-01 study. Of the 149 patients evaluated, 48 (32%) received any concomitant ATB therapy. The ATB class most commonly administered was fluoroquinolones (16 patients; 33%). In the ATB cohort, seven patients (15%) achieved ypT0N0 status, compared to 50 (50%; p < 0.001) in the untreated group. Moreover, ATB use was negatively associated with ypT0N0 status (odds ratio 0.18, 95% confidence interval [CI] 0.05–0.48; p = 0.001). The 24-mo RFS rate was 63% (95% CI 48-83%) in the ATB group versus 90% (95% CI 83–97) in the untreated group. We found that ATB use was associated with a higher recurrence rate (hazard ratio [HR] 2.64, 95% CI 1.08–6.50; p = 0.03). Exploratory analyses showed that fluoroquinolone use was associated with a higher recurrence rate (HR 3.28, 95% CI 1.12–9.60; p = 0.03). Our study revealed an association between ATB use and neoadjuvant immunotherapy efficacy in an intention-to-cure population, highlighting the need for future studies to better investigate this relationship. Patient summary: The efficacy of immunotherapy for cancer is influenced by several patient and tumor factors, including the use of antibiotics. We found that antibiotics taken at the same time as immunotherapy drugs were associated with lower rates of complete response and of recurrence-free survival among patients with muscle-invasive bladder cancer. These findings need to be confirmed in future studies.

Background In patients with muscle-invasive urothelial bladder cancer (MIBC), molecular alterations in immunotherapy-resistant tumors found at radical cystectomy (RC) remain largely unstudied. Objective To investigate the biology of pembrolizumab-resistant tumors in comparison to an RC cohort treated without any systemic therapy and a cohort of neoadjuvant chemotherapy (NAC)-treated tumors. Design, setting, and participants Transcriptome-wide expression profiling was performed on 26 RC samples from patients with ypT2–4 disease after pembrolizumab treatment, of which 22 had matched pretherapy samples. Unsupervised consensus clustering (CC) was performed to compare 26 post-pembrolizumab samples with 94 RC samples without neoadjuvant treatment and 21 samples collected from the former tumor bed of NAC-treated patients (scar tissue). Clusters were investigated for their biological and clinical characteristics and were compared to a cohort of post-NAC tumors (n = 133). Outcome measurements and statistical analysis Patient and tumor characteristics were compared between subgroups using χ2 tests and two-sided Wilcoxon rank-sum tests. The primary endpoint was recurrence-free survival. Results and limitations Molecular subtyping of pre- and post-pembrolizumab samples revealed significant differences: only 36% of samples had a concordant subtype according to the consensus classifier. Unsupervised CC revealed three distinct post-pembrolizumab clusters (basal, luminal, and scar-like). A scar-like subtype was present in 50% of the post-pembrolizumab cases (n = 13) and expressed genes associated with wound healing/scarring. This subtype had higher luminal marker expression in the post-pembrolizumab setting compared to CC scar-like tumors from the other cohorts. Patients with the scar-like subtype showed favorable prognosis after systemic therapy, but not in the RC-only setting. The small numbers in each subgroup represents the major study limitation. Conclusions This study expands our understanding of the biology of pembrolizumab-resistant MIBC and provides a framework for defining molecular subtypes after treatment. The results further support the hypothesis that luminal-type tumors may be resistant to immunotherapy or that this treatment may select for, or induce, a luminal phenotype. Patient summary We carried out genetic analysis for bladder cancer tumors from patients who had received an immunotherapy agent called pembrolizumab and compared them to tumors treated with standard chemotherapy or just bladder removal. We found differences in gene expression between the treatment types and between tumor tissue from the same patient before and after treatment. These results may be helpful in personalizing therapy strategies for patients with bladder cancer.

The similar clinical behavior, overlapping therapeutic patterns, and several clinical trials addressing the neoadjuvant and first-line therapy settings for bladder cancer support the call for a more uniform definition of "locally advanced" disease. We highlight the diverse therapeutic opportunities that patients with locally advanced bladder cancer may receive at present. Multimodal management, and post-therapy surgery in particular, may still have a role in selected patients.

The coronavirus 2019 (COVID-19) pandemic has led to an unprecedented emergency scenario for all aspects of health care, including urology. At the time of writing, Italy was the country with the highest rates of both infection and mortality. A panel of experts recently released recommendations for prioritising urologic surgeries in a low-resource setting. Of note, major cancer surgery represents a compelling challenge. However, the burden of these procedures and the impact of such recommendations on urologic practice are currently unknown. To fill this gap, we assessed the yearly proportion of high-priority major uro-oncologic surgeries at three Italian high-volume academic centres. Of 2387 major cancer surgeries, 32.3% were classified as high priority (12.6% of radical nephroureterectomy, 17.3% of nephrectomy, 33.9% of radical prostatectomy, and 36.2% of radical cystectomy cases). Moreover, 26.4% of high-priority major cancer surgeries were performed in patients at higher perioperative risk (American Society of Anesthesiologists score ≥3), with radical cystectomy contributing the most to this cohort (50%). Our real-life data contextualise ongoing recommendations on prioritisation strategies during the current COVID-19 pandemic, highlighting the need for better patient selection for surgery. We found that approximately two-thirds of elective major uro-oncologic surgeries can be safely postponed or changed to another treatment modality when the availability of health care resources is reduced. PATIENT SUMMARY: We used data from three high-volume Italian academic urology centres to evaluate how many surgeries performed for prostate, bladder, kidney, and upper tract urothelial cancer can be postponed in times of emergency. We found that approximately two-thirds of patients with these cancers do not require high-priority surgery. Conversely, of patients requiring high-priority surgery, approximately one in four is considered at high perioperative risk. These patients may pose challenges in allocation of resources in critical scenarios such as the current COVID-19 pandemic.

UNLABELLED: Active surveillance (AS) represents a well-recognized management option for many patients with low- and very low-risk prostate cancer (PCa). AS aims to reduce overtreatment whilst ensuring curative treatment for those in whom it is needed, without losing the window of curability. While long-term series have confirmed the safety of AS in carefully selected patients, this has resulted in new clinical questions. Can the inclusion criteria be expanded? Is there a role for biomarkers and multiparametric magnetic resonance imaging at diagnosis or during AS? What is the optimal follow-up schedule as well as the most meaningful trigger for definitive treatment? These questions, together with increasingly adopted heterogeneous protocols in AS, have prompted the European Association of Urology to produce a position paper corroborated by a summary of the scientific background on AS. PATIENT SUMMARY: Active surveillance (AS) is becoming a widely adopted strategy for patients affected by low-risk prostate cancer. While a formal systematic review on the topic will soon be available, the European Association of Urology has produced specific statements for different open questions on AS. ispartof: EUROPEAN UROLOGY vol:74 issue:3 pages:357-368 ispartof: location:Switzerland status: published

Using institutional data, we have previously developed an algorithm to identify the optimal candidates for adjuvant radiotherapy (aRT) among men with pN1 prostate cancer (PCa) at radical prostatectomy (RP). This study aimed to test the external validity of our previous findings using a nationwide database while focusing on overall mortality as an endpoint. To this end, we identified 5498 pN1 PCa patients who were treated with RP, pelvic lymph node dissection, and androgen deprivation therapy with or without aRT, within the National Cancer Database, between 2004 and 2015. Patients were divided into five groups based on our previously published algorithm. Similar to our previous report, multivariable Cox regression analysis showed that only two of these groups benefit from aRT: (1) those with one to two positive nodes, pathological Gleason score 7-10, and pT3b/4 disease or positive surgical margins (hazard ratio [HR]=0.75); and (2) those with three to four positive nodes, regardless of local tumor characteristics (HR=0.57, both p=0.01). In the remaining patients (25% of the cohort), aRT had no significant survival benefit. Results were confirmed on sensitivity analyses using 1:1 propensity score-matched cohorts, excluding men who died within 3 yr of surgery and using cut-off of 6 mo post-surgery to identify receipt of aRT. Our findings corroborate the validity of our previously published criteria and highlight the importance of patient selection in pN1 PCa patients who are considered for aRT.

The rate of postoperative complications might vary according to the method used to collect perioperative data. We aimed at assessing the impact of the prospective implementation of the European Association of Urology (EAU) guidelines on reporting and grading of complications in prostate cancer patients undergoing robot-assisted radical prostatectomy (RARP). From September 2016, an integrated method for reporting surgical morbidity based on the EAU guidelines was implemented at a single, tertiary center. Perioperative data were prospectively and systematically collected during a patient interview at 30 d after surgery as recommended by the EAU Guidelines Panel Recommendations on Reporting and Grading Complications. The rate and grading of complications of 167 patients who underwent RARP±pelvic lymph node dissection (PLND) after the implementation of the prospective collection system (Group 1) were compared with 316 patients treated between January 2015 and August 2016 (Group 2) when a system based on patient chart review was used. No differences were observed in disease characteristics and PLND between the two groups (all p≥0.1). Postoperative complications were graded according to the Clavien-Dindo classification system. Overall, the complication rate was higher when the prospective collection system based on the EAU guidelines was used (29%) than when retrospective chart review (10%; p0.001) was used. In particular, a substantially higher rate of grade 1 (8.4% vs 4.7%) and 2 (14% vs 2.8%) complications was detected in Group 1 versus Group 2 (p0.001). Although the rate of complications occurred during hospitalization did not differ (13% vs 10%; p=0.3), 31 (19%) complications after discharge were detected in Group 1. This resulted into a readmission rate of 16%. Conversely, no complications after discharge and readmissions were recorded for Group 2. The implementation of the EAU guidelines on reporting perioperative outcomes roughly doubled the complication rate after RARP and allowed for the detection of complications after discharge in more than 15% of patients that would have been otherwise missed, where patients assessed with the EAU implemented protocol had a threefold higher likelihood of reporting complications.The implementation of the European Association of Urology guidelines on reporting and grading of complications after urologic procedures in prostate cancer patients roughly doubled the complication rate after robot-assisted radical prostatectomy compared to retrospective patient chart review. Moreover, it allowed for the detection of complications after discharge in more than 15% of patients that would have been otherwise missed.

Background: Salvage radiation therapy (SRT) is a recommended treatment option for biochemical recurrence after radical prostatectomy (RP). However, its effectiveness may be limited to specific categories of patients. Objective: We aimed to identify the optimal candidates for early SRT after RP. Design, setting, and participants: The study included 925 node-negative patients treated with SRT after RP at seven institutions. Patients received SRT for either prostate-specific antigen (PSA) rising, or PSA persistence after RP that was defined as PSA level ≥0.1 ng/ml at 1 mo after surgery. All patients received local radiation to the prostate and seminal vesicle bed. Outcome measurements and statistical analysis: The primary outcome measured was distant metastasis after SRT. Regression tree analysis was used to develop a risk-stratification tool. Multivariable Cox regression analysis and nonparametric curve fitting methods were used to explore the relationship between PSA level at SRT and the probability of metastasis-free survival at 8 yr. Results and limitations: At a median follow-up of 8.0 yr, 130 patients developed distant metastasis. At multivariable analysis, pre-SRT PSA level was significantly associated with distant metastasis (hazard ratio: 1.06, p < 0.0001). However, when patients were stratified into five risk groups using regression tree analysis (area under the curve: 85%), early SRT administration provided better metastasis-free survival in three groups only: (1) low risk: undetectable PSA after RP, Gleason score ≤7, and tumour stage ≥pT3b, (2) intermediate risk: undetectable PSA after RP with Gleason score ≥8, (3) high risk: PSA persistence after RP with Gleason score ≤7. Conclusions: We developed an accurate risk stratification tool to facilitate the individualised recommendation for early SRT based on prostate cancer characteristics. Early SRT proved to be beneficial only in selected groups of patients who are more likely to be affected by clinically significant but not yet systemic recurrence at the time of salvage treatment administration. Patient summary: In patients affected by prostate cancer recurrence after radical prostatectomy, the early administration of salvage radiation therapy is beneficial only for selected subgroups of patients. In this study, these groups of patients were identified. In this multi-institutional study, we developed a prognostic tool to assess the risk of distant metastases after early salvage radiation therapy for prostate-specific antigen (PSA) rise after prostatectomy. Five distinct risk groups were identified based on clinical and pathological characteristics. Early salvage radiation therapy administration was noted to be associated with improved cancer control for low-, intermediate-, and high-risk patients. Conversely, very low-risk (undetectable PSA after radical prostatectomy, Gleason score ≤7, and tumour stage ≤pT3a) and very high-risk patients (PSA persistence after radical prostatectomy, and Gleason score ≥8) did not benefit from early salvage treatment. These findings facilitate the identification of optimal candidates for early salvage radiation therapy, and, pending validation, application into clinical practice will help to maximise cancer control while avoiding overtreatment.

Robotic partial nephrectomy (RPN) has a significant morbidity. Nephrometry scores have been described to predict the occurrence of complications. Their usefulness is debated.To evaluate the clinical utility of three nephrometry scores (radius, exophytic/endophytic, nearness, anterior/posterior, location [RENAL], preoperative aspects and dimensions used for an anatomical [PADUA], and simplified PADUA Renal [SPARE]) to predict perioperative outcomes and compare their performance to the simple measurement of tumor size in a large cohort of patients who underwent RPN.We analyzed 1581 consecutive patients who underwent RPN for small renal masses.Tumor size, RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Correlation between scores, estimated blood loss (EBL), operative time (OT), and warm ischemia time (WIT) were calculated. Logistic regression analyses were performed to identify predictors of overall and major complications. The area under the curve was used to identify models with the highest discrimination. Decision curve analyses determined the net benefit associated with their use.The median age was 62 yr (interquartile range [IQR]: 52-70) and the median tumor size was 35 mm (IQR: 25-47). Postoperative complications were observed in 346 patients (21.9%), including 5.6% of major complications. All scores were significantly correlated with EBL, OT, and WIT. However, correlation coefficients were all0.3, suggesting a weak association. Nephrometry scores and tumor size were significant predictors of overall complications in univariate and adjusted multivariable logistic regression model analysis. However, decision curve analysis demonstrated net benefit of tumor size comparable with all nephrometry scores. Finally, neither nephrometry scores nor tumor size was found to be associated with the risk of major complications.Tumor size has the same ability as nephrometry scores to predict perioperative outcomes of RPN.We evaluated the association between tumor size, nephrometry scores, and perioperative outcomes of robotic partial nephrectomy (RPN). We found that tumor size could predict perioperative outcomes of RPN as well as nephrometry scores.