Search

In men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy.To determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy.We analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years.Patients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely.We can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.

Objectives: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini’s nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. Methods: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini’s nomogram were applied to each approach predicting renal function loss at all the specific timeframes. Results: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was

Context The variability of the positive predictive value (PPV) represents a significant factor affecting the diagnostic performance of multiparametric magnetic resonance imaging (mpMRI). Objective To analyze published studies reporting mpMRI PPV and the reasons behind the variability of clinically significant prostate cancer (csPCa) detection rates on targeted biopsies (TBx) according to Prostate Imaging Reporting and Data System (PI-RADS) version 2 categories. Evidence acquisition A search of PubMed, Cochrane library’s Central, EMBASE, MEDLINE, and Scopus databases, from January 2015 to June 2020, was conducted. The primary and secondary outcomes were to evaluate the PPV of PI-RADS version 2 in detecting csPCa and any prostate cancer (PCa), respectively. Individual authors’ definitions for csPCa and PI-RADS thresholds for positive mpMRI were accepted. Detection rates, used as a surrogate of PPV, were pooled using random-effect models. Preplanned subgroup analyses tested PPV after stratification for PI-RADS scores, previous biopsy status, TBx technique, and number of sampled cores. PPV variation over cancer prevalence was evaluated. Evidence synthesis Fifty-six studies, with a total of 16 537 participants, were included in the quantitative synthesis. The PPV of suspicious mpMRI for csPCa was 40% (95% confidence interval 36–43%), with large heterogeneity between studies (I2 94%, p Conclusions Our meta-analysis underlines that the PPV of mpMRI is strongly dependent on the disease prevalence, and that the main factors affecting PPV are PI-RADS version 2 scores and prior biopsy status. A substantially low PPV for PI-RADS 3 lesions was reported, while it was still suboptimal in PI-RADS 4 and 5 lesions. Lastly, even if the added value of a systematic biopsy for csPCa is relatively low, this rate can improve patient risk assessment and staging. Patient summary Targeted biopsy of Prostate Imaging Reporting and Data System 3 lesions should be considered carefully in light of additional individual risk assessment corroborating the presence of clinically significant prostate cancer. On the contrary, the positive predictive value of highly suspicious lesions is not high enough to omit systematic prostate sampling.

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown. Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy. Design, setting, and participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016. Outcome measurements and statistical analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM. Results and limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p 10%. Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials. Patient summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery.

BACKGROUND: Ischemia time during partial nephrectomy (PN) is among the greatest determinants of acute kidney injury (AKI). Whether this association is affected by the preoperative risk of AKI has never been investigated.OBJECTIVE: To assess the effect of the interaction between the preoperative risk of AKI and ischemia time on the probability of AKI during PN.DESIGN, SETTING, AND PARTICIPANTS: Data of 944 patients treated with on-clamp PN for cT1 renal tumors were extracted from the Registry of Conservative and Radical Surgery for Cortical Renal Tumor Disease (RECORD2) database, a prospective multicenter project.OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We estimated the preoperative risk of AKI (defined according to the risk/injury/failure/loss/end-stage [RIFLE] criteria) according to age, baseline renal function, clinical stage, preoperative aspects and dimensions used for an anatomical (PADUA) score, and surgical approach. Classification and regression tree (CART) analysis identified patients at "high" and "low" risk of AKI. Finally, we plotted the probability of AKI over ischemia time stratified by the preoperative risk of AKI.RESULTS AND LIMITATIONS: Overall, 235 (25%) patients experienced AKI after surgery. At multivariable analysis, older patients, those with more complex tumors, those with higher baseline function, and those treated with open surgery had an increased risk of AKI (all p ≤ 0.011). According to the first split at CART analysis, patients were categorized as those with "high" and "low" risk of AKI having a probability of >40% or 20 min of ischemia was 13% versus 28% (absolute risk increase 15%). The risk of AKI for high-risk patients who had 20 min of ischemia was 31% versus 77%. This corresponds to an absolute risk increase of 45%. Limitations include retrospective data analyses and lack of surgeons' prior experience.CONCLUSIONS: Ischemia time during PN has different implications for patients with different health status. Clamp time seems less clinically relevant for patients in good conditions who may endure prolonged ischemia with a mild increase in the risk of AKI, whereas frail patients seem to be more vulnerable to ischemic damage even for short clamp time. For individualized intra- and postoperative management, duration of ischemia needs to be questioned in the context of the individual health status.PATIENT SUMMARY: Functional sequelae related to ischemia time during partial nephrectomy depend on baseline health status. The correlation between the duration of ischemia and baseline health status should be taken into account toward individualized intra- and postoperative management.

Patient-reported outcome instruments for erectile function often ask respondents about their experience over the previous 4wk. This is problematic for baseline assessment of patients with prostate cancer (PC) before treatment, as the previous 4wk would probably have involved procedures such as biopsy and considerable anxiety related to their diagnosis. At San Raffaele Hospital, the International Index of Erectile Function (IIEF-6) was used to ask new PC patients about function in both the previous 4wk and 6mo. We compared responses to these two timeframes. IIEF-6 scores were lower for the 4-wk period (median 24 vs 26; p

Whether early ligation of the dorsal venous complex (DVC) might improve recovery of urinary continence (UC) after robot-assisted radical prostatectomy (RARP) has never been investigated in a prospective randomized study.To assess whether early DVC ligation might affect UC recovery after RARP.DVC ligation (early vs standard).A total of 312 patients with prostate cancer underwent primary RARP at a tertiary care institution.The primary outcome was UC recovery at 1 and 4 mo after RARP. UC was defined as 0 pads/1 safety pad per day. All patients completed the International Prostate Symptom Score (IPSS) and International Consultation of Incontinence Questionnaire (ICIQ)-Short Form questionnaires. Secondary outcomes were early (≤4 mo) erectile function recovery, the positive surgical margin (PSM) rate, 30-d Clavien-Dindo complications, and biochemical recurrence rates. Quality of life was assessed using the EQ-5D-5L questionnaire. The association between treatment arm and UC recovery was also tested using multivariable regression models.After surgery, 23 patients withdrew their consent and 29 were lost to follow-up, leaving 261 patients available for per-protocol analyses. Of these, 32 patients (24%) in the experimental group and 37 (29%) in the control group used no pad/one safety pad at 1 mo after RARP, whereas 96 (72%) in the control group versus 83 (65%) in the control group were continent at 4-mo follow-up (both p = 0.3). Median ICIQ and IPSS scores did not differ between the groups at both time points. The results were confirmed on multivariable regression analyses. PSMs were observed for 32 patients (25%) in the experimental group versus 30 (22%) in the control group (p = 0.6). The incidence of postoperative complications (17% experimental vs 13% control) and the 1-yr biochemical recurrence-free survival did not differ between the groups.In this randomized clinical trial, we did not find evidence that early ligation of the DVC during RARP was associated with better UC recovery after surgery in comparison to the standard technique. Given its safety in terms of surgical margins and complications, this technique may be considered as an option for surgical dissection according to the physician's preference.Our trial showed that for patients undergoing robot-assisted surgical removal of the prostate, the timing of a specific step to control bleeding from a network of veins draining the prostate did not affect recovery of urinary continence after surgery. The results indicate that earlier control of these veins may be considered as an option according to the surgeon's preference.

Background/Aims: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. Methods: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). Results: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). Conclusions: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.

To examine the effect of frailty on short-term post-operative outcomes and total hospital charges (THCs) in patients with non-metastatic renal cell carcinoma, treated with partial nephrectomy (PN).Within the National Inpatient Sample (NIS) database we identified 25,545 patients treated with PN from 2000 to 2015. We used the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining indicator and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, blood transfusions, non-home-based discharge, length of stay (LOS) and THCs. Time trends and multivariable logistic, Poisson and linear regression models were applied.Overall, 3574 (14.0%) patients were frail, 2677 (10.5%) were older than 75 years and 2888 (11.3%) had Charlson comorbidity index (CCI) ≥ 2. However, the vast majority of frail patients were neither elderly nor comorbid (83%). Rates of frail patients treated with PN increased over time, from 8.3 in 2000 to 18.1% in 2015 (all p lt; 0.001). Frail patients showed higher rates of overall complications (43.5 vs. 30.3%), major complications (16.6 vs. 9.8%), blood transfusions (11.6 vs 8.3%) and non-home-based discharge (9.9 vs. 5.4%). longer LOS [4 (IQR: 3-6) vs. 4 (IQR: 2-5) days] and higher THCs ($43,906 vs. $38,447 - all p lt; 0.001). Moreover, frailty status independently predicted overall complications (OR: 1.73), major complications (OR: 1.63), longer LOS (RR: 1.07) and higher THCs (RR: +$7506). Finally, a dose-response on the risk of suboptimal surgical outcomes was shown in patients with multiple risk factors.One out of seven patients is frail at time of surgery and this rate is on the rise. Moreover, frailty is associated with adverse outcomes after PN. In consequence, preoperative assessment of frailty status should be implemented, to identify patients who may benefit from pre- or postoperative measures aimed at improving surgical outcomes in this patient population.

Whether or not adding systematic biopsies (transrectal ultrasound-guided biopsy [TRUS-Bx]) to targeted cores in patients with a lesion detected at multiparametric magnetic resonance imaging (mpMRI) is still a debated topic.To identify patients who can avoid TRUS-Bx at the time of mpMRI targeted biopsy (MRI-TBx) relying on individual patient probability to harbour clinically significant prostate cancer (csPCa) outside the index lesion (IL).A total of 339 European and 441 North American patients underwent fusion MRI-TBx and concomitant TRUS-Bx at two tertiary care referral centres between 2013 and 2017.The study outcome was csPCa, defined as a Gleason score at biopsy of ≥7, outside the IL. Multivariable logistic regression analyses (MVAs) were performed to develop a predictive model for the study outcome. Multivariable-derived coefficients were used to develop a novel risk calculator in each cohort. The models were evaluated using the area under the curve (AUC), calibration plot, and decision-curve analyses.In the European cohort, csPCa detection rate was 55%. The csPCa detection rate for TRUS-Bx was 41%. At MVAs, prostate volume, previous negative biopsy, and Prostate Imaging Reporting and Data System versions 4 and 5 were independent predictors for the presence of csPCa outside the IL. The multivariable model had an AUC of 0.78. Omitting TRUS-Bx in patients with a calculated risk of15% would have spared 16% of TRUS-Bx at the cost of missing 7% of csPCa. Similar findings were obtained when the same analyses were performed in the North American cohort. No net benefit was observed for low-threshold probabilities (15%) of the each model relative to the standard of care (performing TRUS-Bx in addition to MRI-TBx to all patients) in both cohorts. The study is limited by its retrospective design.We failed to identify those patients who might safely benefit from MRI-TBx alone. The combination of MRI-TBx and TRUS-Bx should strongly be considered the best available approach.In the presence of positive multiparametric magnetic resonance imaging (mpMRI) of the prostate, physicians should always perform systematic sampling of the prostate in addition to mpMRI targeted biopsy.

Background The impact of positive surgical margins (PSMs) on the risk of metastases in prostate cancer (PCa) patients treated with radical prostatectomy (RP) is still debated. Objective To identify PSM features associated with recurrence in a stage-by-stage analysis. Design, setting, and participants A total of 1757 PCa patients treated with RP without neoadjuvant or adjuvant treatments between 2011 and 2017 were identified. Patients were stratified according to the presence of PSM and to margins characteristics in three groups: no versus favourable (single margin Outcome measurements and statistical analysis Predictors of biochemical recurrence (BCR) and clinical recurrence (CR) were assessed using semiparametric Cox proportional hazard models. Results and limitations Overall, 285 (16%) patients had PSMs; 146 (51%) had a unifocal PSM, while 139 (49%) had a multifocal PSM. The median length of a PSM was 1 mm. Overall, 120 (42%) versus 165 (58%) patients had favourable versus unfavourable PSMs. In patients with ≤pT3a and pathologic grade group ≤3 disease (n = 1351), favourable (hazard ratio [HR]: 2.24; 95% confidence interval [CI]: 1.19–4.22) and unfavourable (HR: 2.68; 95% CI: 1.49–4.84) PSMs significantly increased the risk of BCR (p 0.05). Conversely, in patients with pT3b/4 and/or pathologic grade group 4–5 and/or pN1 (n = 406), only an unfavourable PSM was associated with both BCR (HR: 2.96; 95% CI: 1.19–4.22) and CR (HR: 2.60; 95% CI: 1.07–6.30; all p ≤ 0.04). Conclusions Although the presence of PSMs was associated with an increased risk of BCR in all stages, only men with adverse pathologic characteristics and an unfavourable PSM were at an increased risk of experiencing metastases as compared with their counterparts with no or a single margin shorter than 3 mm. Patient summary In this study, we defined a new category of unfavourable positive surgical margins (namely, ≥3 mm and/or multifocal), which confers a higher risk of developing metastasis in men with more aggressive pathologic features.

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.

OBJECTIVE: To examine the predictive value of neutrophil-to-lymphocyte ratio in localized prostate cancer for surgical pathology and recurrence in patients treated by radical prostatectomy PATIENTS AND METHODS: We evaluated 1 258 patients treated by radical prostatectomy at San Raffaele Hospital between 2011 and 2017 and assessed the association between preoperative neutrophil-to-lymphocyte ratio and surgical pathology (advanced stage, grade group ≥4, nodal involvement, grade discordance between biopsy and surgical pathology) and biochemical recurrence. RESULTS: The preoperative neutrophil-to-lymphocyte ratio was not significantly associated with advanced stage (≥T3), International Society of Urological Pathology (ISUP) grade (≥4) or discordance. At multivariable analysis, patients with higher neutrophil-to-lymphocyte ratio had lower risk of nodal involvement at final pathology (odds ratio [OR]: 0.77; 95% confidence interval [CI]: 0.64, 0.92; P=0.005). The preoperative level of neutrophil-to-lymphocyte ratio was associated with biochemical recurrence on univariate analysis (OR: 0.81, 95% CI: 0.68, 0.96; P=0.017). Such a relationship was not significant at multivariable analysis adjusting for tumor severity (OR: 0.93, 95% CI: 0.79, 1.09; P=0.4). CONCLUSIONS: Neutrophil-to-lymphocyte ratio does not have clinical utility for the prediction of adverse pathology and biochemical recurrence. Further research should focus on its value for predicting regional lymph node metastasis

Background In men with node-positive prostate cancer after radical prostatectomy there are limited data on the value of adding androgen deprivation therapy (ADT) to postoperative radiotherapy. Objective To determine whether there is a clear oncologic benefit to ADT in the setting of node-positive prostate cancer treated with postoperative radiotherapy. Methods We analyzed data for 372 prostate cancer patients treated at San Raffaele Hospital with postoperative radiotherapy for node-positive disease after radical prostatectomy, 272 received both ADT and radiotherapy. Eighty-six men were followed without an event for more than 10 years. Results Patients who received postoperative radiotherapy + ADT had more aggressive disease, with higher preoperative PSA level, higher rate of ISUP grade 5, pT3b-T4 tumors and ≥3 positive nodes. At multivariable Cox regression, the comparison between men treated by postoperative radiotherapy + ADT vs. radiotherapy alone did not show a significant difference for overall (hazards ratio: 0.91; 95% confidence interval: 0.45, 1.84; P = 0.8) and cancer-specific survival (hazards ratio: 5.39; 95% confidence intervalI: 0.70, 41.39; P = 0.11). These results remained consistent in a number of sensitivity analyses, including propensity score matching. Consideration of 95% CIs suggests that a clinically significant benefit of ADT in node-positive patients receiving radiotherapy after surgery is unlikely. Conclusions We can exclude the sort of large survival benefit that would be required to justify the risks and toxicities of ADT in men with node-positive disease receiving postoperative radiotherapy. Awaiting larger and more powered studies on this topic, men with pN+ prostate cancer treated with postoperative radiotherapy should not receive ADT outside well-controlled clinical trials.

Background: Salvage lymph node dissection (SLND) represents a possible treatment option for prostate cancer patients affected by nodal recurrence after local treatment. However, SLND may be associated with intra- and postoperative complications, and the oncological benefit may be limited to specific groups of patients. Objective: To identify the optimal candidates for SLND based on preoperative characteristics. Design, setting, and participants: The study included 654 patients who experienced prostate-specific antigen (PSA) rise and nodal recurrence after radical prostatectomy (RP) and underwent SLND at nine tertiary referral centers. Lymph node recurrence was documented by positron emission tomography/computed tomography (PET/CT) scan using either 11C-choline or 68Ga-labeled prostate-specific membrane antigen ligand. Intervention: SLND. Outcome measurements and statistical analysis: The study outcome was early clinical recurrence (eCR) developed within 1 yr after SLND. Multivariable Cox regression analysis was used to develop a predictive model. Multivariable-derived coefficients were used to develop a novel risk calculator. Decision-curve analysis was used to evaluate the net benefit of the predictive model. Results and limitations: Median follow-up was 30 (interquartile range, 16–50) mo among patients without clinical recurrence (CR), and 334 patients developed CR after SLND. In particular, eCR at 1 yr after SLND was observed in 150 patients, with a Kaplan-Meier probability of eCR equal to 25%. The development of eCR was significantly associated with an increased risk of cancer-specific mortality at 3 yr, being 20% versus 1.4% in patients with and without eCR, respectively (p < 0.0001). At multivariable analysis, Gleason grade group 5 (hazard ratio [HR]: 2.04; p < 0.0001), time from RP to PSA rising (HR: 0.99; p = 0.025), hormonal therapy administration at PSA rising after RP (HR: 1.47; p = 0.0005), retroperitoneal uptake at PET/CT scan (HR: 1.24; p = 0.038), three or more positive spots at PET/CT scan (HR: 1.26; p = 0.019), and PSA level at SLND (HR: 1.05; p < 0.0001) were significant predictors of CR after SLND. The coefficients of the predictive model were used to develop a risk calculator for eCR at 1 yr after SLND. The discrimination of the model (Harrel's C index) was 0.75. At decision-curve analysis, the net benefit of the model was higher than the “treat-all” option at all the threshold probabilities. Conclusions: We reported the largest available series of patients treated with SLND. Roughly 25% of men developed eCR after surgery. We developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach. Patient summary: The risk of early recurrence after salvage lymph node dissection (SLND) was approximately 25%. In this study, we developed a novel tool to predict the risk of early failure after SLND. This tool will be useful to identify patients who would benefit the most from SLND from other patients who should be spared from surgery. We reported the largest available series of patients treated with salvage lymph node dissection (SLND), and we developed the first risk stratification tool to identify the optimal candidate to SLND based on routinely available preoperative characteristics. This tool can be useful to avoid use of SLND in men more likely to progress despite any imaging-guided approach.

Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.

Background Preoperative assessment of the risk of lymph node invasion (LNI) is mandatory to identify prostate cancer (PCa) patients who should receive an extended pelvic lymph node dissection (ePLND). Objective To update a nomogram predicting LNI in contemporary PCa patients with detailed biopsy reports. Design, setting, and participants Overall, 681 patients with detailed biopsy information, evaluated by a high-volume uropathologist, treated with radical prostatectomy and ePLND between 2011 and 2016 were identified. Outcome measurements and statistical analysis A multivariable logistic regression model predicting LNI was fitted and represented the basis for a coefficient-based nomogram. The model was evaluated using the receiver operating characteristic-derived area under the curve (AUC), calibration plot, and decision-curve analyses (DCAs). Results and limitations The median number of nodes removed was 16. Overall, 79 (12%) patients had LNI. A multivariable model that included prostate-specific antigen, clinical stage, biopsy Gleason grade group, percentage of cores with highest-grade PCa, and percentage of cores with lower-grade disease represented the basis for the nomogram. After cross validation, the predictive accuracy of these predictors in our cohort was 90.8% and the DCA demonstrated improved risk prediction against threshold probabilities of LNI ≤20%. Using a cutoff of 7%, 471 (69%) ePLNDs would be spared and LNI would be missed in seven (1.5%) patients. As compared with the Briganti and Memorial Sloan Kettering Cancer Center nomograms, the novel model showed higher AUC (90.8% vs 89.5% vs 89.5%), better calibration characteristics, and a higher net benefit at DCA. Conclusions An ePLND should be avoided in patients with detailed biopsy information and a risk of nodal involvement below 7%, in order to spare approximately 70% ePLNDs at the cost of missing only 1.5% LNIs. Patient summary We developed a novel nomogram to predict lymph node invasion (LNI) in patients with clinically localized prostate cancer based on detailed biopsy reports. A lymph node dissection exclusively in men with a risk of LNI > 7% according to this model would significantly reduce the number of unnecessary pelvic nodal dissections with a risk of missing only 1.5% of patients with LNI. Our study reports an accurate model predicting lymph node invasion in patients with localized prostate cancer. The implementation of this model in clinical practice would reduce the number of unnecessary lymph node dissections.