Multivariable stratification of PI-RADS version 2.1 categories for the risk of false-positive target biopsy: Impact on prostate biopsy decisions.

PURPOSE: To identify clinical and multiparametric magnetic resonance imaging (mpMRI) factors predicting false positive target biopsy (FP-TB) of prostate imaging reporting and data system version 2.1 (PI-RADSv2.1) ≥ 3 findings. METHOD: We retrospectively included 221 men with and without previous negative prostate biopsy who underwent 3.0 T/1.5 T mpMRI for suspicious clinically significant prostate cancer (csPCa) between April 2019-July 2021. A study coordinator revised mpMRI reports provided by one of two radiologists (experience of > 1500/>500 mpMRI examinations, respectively) and matched them with the results of transperineal systematic biopsy plus fusion target biopsy (TB) of PI-RADSv2.1 ≥ 3 lesions or PI-RADSv2.1 ≤ 2 men with higher clinical risk. A multivariable model was built to identify features predicting FP-TB of index lesions, defined as the absence of csPCa (International Society of Urogenital Pathology [ISUP] ≥ 2). The model was internally validated with the bootstrap technique, receiving operating characteristics (ROC) analysis, and decision analysis. RESULTS: Features significantly associated with FP-TB were age < 65 years (odds ratio [OR] 2.77), prostate-specific antigen density (PSAD) < 0.15 ng/mL/mL (OR 2.45), PI-RADS 4/5 category vs. category 3 (OR 0.15/0.07), and multifocality (OR 0.46), with a 0.815 area under the curve (AUC) in assessing FP-TB. When adjusting PI-RADSv2.1 categorization for the model, mpMRI showed 87.5% sensitivity and 79.9% specificity for csPCa, with a greater net benefit in triggering biopsy compared to unadjusted categorization or adjustment for PSAD only at decision analysis, from threshold probability ≥ 15%. CONCLUSION: Adjusting PI-RADSv2.1 categories for a multivariable risk of FP-TB is potentially more effective in triggering TB of index lesions than unadjusted PI-RADS categorization or adjustment for PSAD alone.

Sacrocolpopexy after sub-total hysterectomy vs. sacral hysteropexy for advanced urogenital prolapse: A propensity-matched study.

OBJECTIVE: To compare objective and subjective outcomes of laparoscopic sacral colpopexy with supracervical hysterectomy (L-SCP) and robotic sacral hysteropexy (R-SHP). METHODS: This is a multicenter retrospective propensity score matched study. In the period between January 2014 and December 2018, we enrolled 161 patients with apical prolapse stage 2 or above, alone or with multicompartment descensus. RESULTS: After propensity-match analysis, there were 44 women for each group. Patients of the two groups had similar preoperative characteristics. No difference was found in terms of estimated blood loss, hospital stay, operative time, and intraoperative or postoperative complications. Subjective success rate, 12 months after surgery, was statistically better in the L-SCP group (P = 0.034): 81.8% and 97.8% women had Patient Global Impression of Improvement scores less than 3, in R-SHP and L-SCP, respectively. The objective cure rate was high in both groups without any significant differences in recurrence rate (P = 0.266). CONCLUSION: Both procedures are safe and effective in pelvic organ prolapse treatment. Patients who no longer desire uterine preservation could be encouraged to consider L-SCP. R-SHP is an alternative in women who are strongly motivated to preserve their uterus in the absence of abnormal uterine findings.

Effect of Preoperative Multiparametric Magnetic Resonance Imaging on Oncologic and Functional Outcomes Following Radical Prostatectomy.

Background: Advancements in imaging technology have been associated with changes to operative planning in treatment of localized prostate cancer. The impact of these changes on postoperative outcomes is understudied. Objective: To compare oncologic and functional outcomes between men who had computed tomography (CT) and those who had multiparametric magnetic resonance imaging (mpMRI) prior to undergoing radical prostatectomy. Design setting and participants: In this retrospective cohort study, we identified all men who underwent radical prostatectomy (n = 1259) for localized prostate cancer at our institution between 2009 and 2016. Of these, 917 underwent preoperative CT and 342 mpMRI. Outcome measurements and statistical analysis: Biochemical recurrence-free survival, positive margin status, postoperative complications, and 1-yr postprostatectomy functional scores (using the 26-item Expanded Prostate Cancer Index Composite [EPIC-26] questionnaire) were compared between those who underwent preoperative CT and those who underwent mpMRI using propensity score weighted Cox proportional hazard regression, logistic regression, and linear regression models. Results and limitations: Baseline and 1-yr follow-up EPIC-26 data were available for 449 (36%) and 685 (54%) patients, respectively. After propensity score weighting, no differences in EPIC-26 functional domains were observed between the imaging groups at 1-yr follow-up. Positive surgical margin rates (odds ratio 1.03, 95% confidence interval [CI] 0.77-1.38, p = 0.8) and biochemical recurrence-free survival (hazard ratio 1.21, 95% CI 0.84-1.74, p = 0.3) were not significantly different between groups. Early and late postoperative complications occurred in 219 and 113 cases, respectively, and were not different between imaging groups. Our study is limited by a potential selection bias from the lack of functional scores for some patients. Conclusions: In this single-center study of men with localized prostate cancer undergoing radical prostatectomy, preoperative mpMRI had minimal impact on functional outcomes and oncologic control compared with conventional imaging. These findings challenge the assumptions that preoperative mpMRI improves operative planning and perioperative outcomes. Patient summary: In this study, we assessed whether the type of prostate imaging performed prior to surgery for localized prostate cancer impacted outcomes. We found that urinary and sexual function, cancer control, and postoperative complications were similar regardless of whether magnetic resonance imaging or computed tomography was utilized prior to surgery.

Diagnosis of clinically significant prostate cancer after negative multiparametric magnetic resonance imaging.

Introduction: The diagnostic pathway after a negative magnetic resonance imaging (nMRI) exam is not clearly defined. The aim of the present study is to define the risk of prostate adenocarcinoma (PCa) at the prostate biopsy after a negative multiparametric magnetic resonance imaging (mpMRI) exam. Material and methods: Patients with nMRI Prostate Imaging Reporting & Data System (PI-RADS) ≤2 and without a previous diagnosis of PCa were identified among all patients undergoing mpMRI in a single referral center between 01/2016-12/2019. Detailed data about prostate biopsy after nMRI were collected, including any PCa diagnosis and clinically significant PCa diagnosis. [Gleason score (GS) ≥7]. In addition to descriptive statistics, uni and multivariable logistic regression assessed the potential predictors of any PCa and clinically significant prostate cancer (csPCa) at the biopsy after a negative mpMRI. Results: Of 410 patients with nMRI, 73 underwent saturation biopsy. Only prostate-specific antigen (PSA) levels were significantly higher in patients undergoing biopsy (5.2 ng/ml vs 6.4, p <0.001), while Prostate Cancer Research Foundation (SWOP - Stichting Wetenschappelijk Onderzoek Prostaatkanker) risk score and other variables did not differ. A total of 22 biopsies (30.1%) were positive for PCa, GS 6 was diagnosed in 14 patients, GS 7 in 3, GS 8 in 1 and GS 9-10 in 4. csPCa was found in 8 (11%) patients. No significant predictors of any PCa or csPCa were identified at multivariate regression analysis. Conclusions: Despite the good negative predictive value of mpMRI in the diagnosis of prostate cancer, 11% of the patients had csPCa. Specific predictive models addressing this setting would be useful.

Metabolic syndrome and prostate cancer treatment.

Metabolic syndrome (MetS) has been linked with several human cancers. Prostate cancer is the most common neoplasm in male adults and is often treated with radical prostatectomy (RP). Given the complex hormonal and metabolic alteration present in MetS, a possible role in the development and progression of prostate cancer (PCa) has been hypothesized. Several studies have investigated the connections between MetS and the risk of developing prostate cancer, as well as the oncological outcomes of patients who already suffer from PCa and receive a radical treatment. This comprehensive review explores the available evidence dealing with MetS and the oncological and functional results of RP for PCa.

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.

Assessing the Clinical Value of Positive Multiparametric Magnetic Resonance Imaging in Young Men with a Suspicion of Prostate Cancer.

BACKGROUND: There is a lack of evidence on the ability of magnetic resonance imaging (MRI) of the prostate to detect clinically significant prostate cancer (csPCa) in young patients. OBJECTIVE: We hypothesised that the diagnostic performance of MRI for csPCa varies according to patient's age. To address this, we assessed the variation in the csPCa detection rate of MRI targeted biopsy (MRI-TBx) versus systematic random biopsy (SBx) across different patient ages. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified 930 patients who underwent prostate MRI and subsequent biopsy at two referral centres between 2013 and 2018. The Prostate Imaging Reporting and Data System (PI-RADS) was used for MRI reporting. INTERVENTION: A lesion with a PI-RADS score of ≥3 detected at MRI received an MRI-TBx in addition to an SBx during the same session. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome of our study was the relationship between age and csPCa detection rate at MRI-TBx and SBx, respectively. Clinically significant prostate cancer (PCa) was defined as the presence of PCa with Gleason score ≥3+4. Multivariable logistic regression analyses (MVAs) predicting csPCa detection were assessed for both MRI-TBx and SBx. Covariates were age, prostate-specific antigen density, PI-RADS score, previous biopsy status, digital rectal examination, and the number of targeted and systematic cores. The hypothesis that MRI accuracy in detecting csPCa differed by age was finally tested with a nonparametric loess analysis. RESULTS AND LIMITATIONS: The overall rate of csPCa was 54% (n=506). Overall, 325 (35%) and 461 (50%) patients had csPCa at SBx and MRI-TBx, respectively. The median numbers of SBx and MRI-TBx cores were 12 (interquartile range [IQR]: 10-13) and 5 (IQR: 4-7), respectively. At MVA, age at biopsy was an independent predictor of csPCa at MRI-TBx only (odds ratio: 1.05), after accounting for confounders. In men aged less than roughly 50yr, SBx had a higher probability of detecting csPCa relative to MRI-TBx (25% vs 16% at 40yr). Conversely, in patients aged >50yr, the probability of csPCa was higher in MRI-TBx than in SBx, reaching the highest difference for very elderly patients (48% vs 68% at 80yr). The main limitations were the retrospective design and the small number of young patients. CONCLUSIONS: In this study, we reported the performance of MRI and MRI-TBx in detecting csPCa changes according to patients' age. PATIENT SUMMARY: In young patients, the performance of a systematic random biopsy in detecting clinically significant prostate cancer (csPCa) is higher relative to magnetic resonance imaging targeted biopsy (MRI-TBx), reflecting the lower accuracy of MRI in younger men. Conversely, in older patients, MRI-TBx showed a clinical benefit with a higher csPCa detection rate compared with SBx, suggesting an increase of MRI accuracy with the increase of age.

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.

Morbidity, mortality, and quality assessment following open radical cystectomy in elderly patients with bladder cancer.

BACKGROUND: Open radical cystectomy (ORC) with pelvic lymph-node dissection (PLND) for bladder cancer (BCa) and urinary diversion is a morbid procedure, and advanced age has been associated with a higher incidence of Clavien-Dindo ≥ 3 complications. AIM: To investigate the association between chronological age, survival outcomes, incidence of perioperative complications, and quality parameters in patients undergoing ORC. METHODS: We reviewed 413 patients who underwent ORC and PLND at a single academic centre between December 2009 and June 2018 for cT2-T4N0M0 BCa. Complete clinical, demographic, and pathological data were collected in the preoperative, preoperative, and postoperative setting. Patients were categorized as ≥ 75 years or < 75 years and statistical analysis was performed accordingly. Besides descriptive statistics, Kaplan-Meier log-rank test was used. Cox regression univariate and multivariate analyses were used to assess any potential predictor of OS and CSS. RESULTS: There were 285 (69%) patients < 75 years and 128 (31%) patients ≥ 75 years old. There was no significant difference between the two age groups neither in terms of distribution of pathological stage nor in terms of overall incidence of postoperative complications. Chronological age was not significantly associated with survival outcomes on multivariate analysis. Finally, the comorbidity index was the only significant risk factor for the incidence of any complications (OR = 0.83, p = 0.002) at multivariate binary logistic regression. CONCLUSION: Open radical cystectomy (ORC) is a feasible and safe procedure in patients with high-risk non-metastatic bladder cancer. Uro-oncologists should consider evaluating elderly patients for surgery according to a thorough geriatric assessment despite chronological age.

Relevance of the Endoscopic Evaluation in the Diagnosis of Bladder Pain Syndrome/Interstitial Cystitis.

OBJECTIVE: To assess the relevance of the endoscopic evaluation in clinically suspected cases of Bladder Pain Syndrome/Interstitial Cystitis (BPS/IC), using ESSIC criteria, established in 2008 by the European Society for the Study of Interstitial Cystitis (ESSIC). METHODS: We included all patients who underwent endoscopic evaluation between January 01, 2015 and October 31, 2019 for clinical suspicion of BPS/IC. Collected data included demographic and baseline clinical features, endoscopic appearance (prior and after hydrodistension), and bladder wall biopsy results, both defined according to ESSIC criteria. Data were cross tabulated to define ESSIC phenotypes, while subgroups and multivariate analyses were carried out to assess the influence of clinical variables on ESSIC phenotypes. RESULTS: Fifty-two subjects were included, mainly women (92%). Median age at evaluation was 45 (32.9-58.2) years. At hydrodistension, 21 patients (42%) had positive and 29 (58%) had negative findings. Grade 2-3 glomerulations were found in 18 patients, while Hunner lesions were reported only in 1 patient. Positive results at biopsy were found in 24 pts (51.1%), while negative in 23 (48.9%). Overall, the positive and negative concordance between hydrodistension and biopsy results was 78%. No significant differences in ESSIC subtypes were found after stratification based on clinical features and at multivariate analysis. Retrospective design is the main limitation. CONCLUSION: Cystoscopy with hydrodistension and biopsy do have a role in the diagnostic pathway of BPS/IC. However, results should be considered in the clinical context of the individual patient.

There Is No Way to Avoid Systematic Prostate Biopsies in Addition to Multiparametric Magnetic Resonance Imaging Targeted Biopsies.

BACKGROUND: 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. OBJECTIVE: 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). DESIGN, SETTING, AND PARTICIPANTS: 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. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: 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. RESULTS AND LIMITATIONS: 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 of <15% 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.

Impact of metabolic syndrome on functional outcomes and complications of surgical treatment of prostate cancer.

BACKGROUND: Metabolic syndrome (MetS) has a negative impact on functional recovery and complications after many surgical procedures. AIM: To assess the role of Mets on functional outcomes and complications after radical prostatectomy (RP) for prostate cancer. PATIENTS AND METHODS: Complete data were collected from 5758 patients, undergoing RP at a single referral centers in a 10-year period and the presence of MetS before surgery was ascertained in 17.7% of them using a modified version of the IDF-AHA/NHLBI criteria. Outcomes included 1-year continence and potency rates, early (≤90 days) and late (>90 days) complications. RESULTS: Postoperative continence (no pads) was significantly less likely in MetS patients (75.4% vs 82.6%, P < .01), despite no difference in preoperative continence. Erections with or without therapy were reached in 55.8% of non-MetS and 41.8% of MetS patients (P < .01), in this case a significant difference in preoperative function was seen. No differences in early and late complications, except for wound infections (5.8% vs 3.9%, P < .01) were observed. CONCLUSIONS: In the present study RP was safe from the complications standpoint in MetS patients, but the presence of the syndrome was a significant risk factor for post-RP incontinence and impotence.

Delaying Radical Cystectomy After Neoadjuvant Chemotherapy for Muscle-invasive Bladder Cancer is Associated with Adverse Survival Outcomes.

BACKGROUND: Delaying radical cystectomy (RC) after a diagnosis of muscle-invasive bladder cancer (MIBC) has been associated with adverse survival. However, data are lacking regarding the impact of RC delay in patients receiving neoadjuvant chemotherapy (NAC). OBJECTIVES: To assess whether the time from last cycle of NAC to RC (time to cystectomy, TTC) is associated with survival among MIBC patients. DESIGN, SETTING, AND PARTICIPANTS: The study cohort comprised 226 patients treated with NAC and RC between 1999 and 2015 for cT2-T4N0M0 bladder cancer. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Descriptive statistics were used to test the association between TTC and clinicopathologic variables. Overall mortality (OM) and cancer-specific mortality (CSM) were analyzed via Kaplan-Meier estimation according to TTC. We assessed factors associated with OM and CSM using multivariable Cox regression analyses. RESULTS AND LIMITATIONS: The median TTC was 7.57wk (interquartile range 5.2-10.8). Patients with a Charlson comorbidity index (CCI) ≥1 had a longer TTC than those with a score of <1 (p=0.027). The group with TTC >10wk had significantly lower OM-free (p=0.003) and CSM-free rates (p<0.001) than the group with TTC ≤10wk. TTC was independently associated with higher risk of OM (p=0.027) and CSM (p=0.004) after accounting for age, gender, pathologic extravesical disease, and nodal status. CONCLUSIONS: TTC of >10wk after NAC was associated with adverse survival among patients with MIBC. Patients with a higher CCI were more likely to have prolonged TTC. PATIENT SUMMARY: The impact of delaying radical cystectomy in patients who have received neoadjuvant chemotherapy (NAC) is unknown. In this study we assessed whether prolonged time to cystectomy (TTC) after NAC affects survival outcomes in patients with muscle-invasive bladder cancer. We found that TTC of >10wk was associated with adverse overall survival and cancer-specific survival, and attempts should be made to shorten TTC after preoperative chemotherapy.

Clinical predictors and survival outcome of patients receiving suboptimal neoadjuvant chemotherapy and radical cystectomy for muscle-invasive bladder cancer: a single-center experience.

PURPOSE: To investigate the prevalence of and factors' association with receiving suboptimal neoadjuvant chemotherapy (NAC) and its impact on survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). METHODS: We reviewed 1119 patients treated with NAC and/or RC for cT2-cT4N0M0 BC. Patients were segregated into three groups: (i) suboptimal NAC (received < 3 cycles of cisplatin-based NAC or non-cisplatin-based regimen), (ii) optimal NAC and (iii) no NAC. Clinical characteristics were compared among groups. Logistic regression analyses tested the association between clinical variables and the odds of receiving suboptimal NAC. To adjust for potential baseline confounders, propensity score matching was performed. Pathologic outcomes were compared between groups and Cox regression analyses tested the risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). RESULTS: Before matching, 84/315 (26.6%) patients received a suboptimal NAC regimen. Lower general health status and impaired renal functions were the most significant factors associated with the administration of a suboptimal NAC. After matching, the optimal NAC group achieved higher rates of complete pathological response as compared to the suboptimal group (p = 0.03). Suboptimal NAC (HR 1.77; p = 0.015) and no NAC (HR 1.52; p = 0.03) were both associated with higher risk of recurrence and OM (HR 1.71; p = 0.02 and HR 1.61; p = 0.02) as compared to optimal NAC. CONCLUSION: One out of four MIBC patients received a suboptimal NAC regimen before RC. Receiving a suboptimal NAC regimen was associated with worse disease recurrence and survival outcomes following surgery, as compared to an optimal NAC regimen.

Assessing the Role and Optimal Duration of Hormonal Treatment in Association with Salvage Radiation Therapy After Radical Prostatectomy: Results from a Multi-Institutional Study.

BACKGROUND: The optimal duration of hormonal therapy (HT) when associated with postprostatectomy radiation therapy (RT) remains controversial. OBJECTIVE: To test the impact of HT duration among patients treated with postprostatectomy RT, stratified by clinical and pathologic characteristics. DESIGN, SETTING, AND PARTICIPANTS: The study included 1264 patients who received salvage RT (SRT) to the prostatic and seminal vesicle bed at eight referral centers after radical prostatectomy (RP). Patients received SRT for either rising prostate-specific antigen (PSA) or PSA persistence after RP, defined as PSA ≥0.1ng/ml at 1mo after surgery. Administration of concomitant HT was at the discretion of the treating physician. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The outcome of interest was clinical recurrence (CR) after SRT, as identified by imaging. Multivariable Cox regression analysis was used to test the association between CR and HT duration. We applied an interaction test between HT duration and baseline risk factors to assess the hypothesis that CR-free survival differed by HT duration according to patient profile. Three risk factors were prespecified for evaluation: pT stage ≥pT3b, pathologic Gleason ≥8, and PSA level at SRT >0.5 ng/ml. The relationship between HT duration and CR-free survival rate at 8yr was graphically explored according to the number of risk factors (0 vs 1 vs ≥2). RESULTS AND LIMITATIONS: Overall, 1125 men (89%) received SRT for rising PSA and 139 (11%) were treated for PSA persistence. Concomitant HT was administered to 363 patients (29%), with a median HT duration of 9mo. At median follow-up of 93mo after surgery, 182 patients developed CR. The 8-yr CR-free survival was 92%. On multivariable analysis, HT duration was inversely associated with the risk of CR (hazard ratio 0.95; p=0.022). A total of 531 (42%) patients had none of the prespecified risk factors, while 507 (40%) had one and 226 (18%) had two or more risk factors. The association between HT duration and CR was significantly different by risk factors (0 vs 1, p=0.001; 0 vs ≥2, p<0.0001). We observed a significant effect of HT duration for patients with two or more risk factors, for whom HT administration was beneficial when given for up to 36mo. This effect was attenuated among patients with one risk factor, with concomitant HT slightly beneficial when administered for a shorter time (<12mo). Conversely, for patients with no risk factors, the risk of CR remained low and constant regardless of HT duration. CONCLUSIONS: The oncologic benefit of HT duration among men receiving SRT for increasing PSA after RP depends on their clinical and pathologic characteristics. Our data suggested a significant effect of long-term HT for patients with two or more adverse features. Conversely, short-term HT was sufficient for patients with a single risk factor, whereas patients without any risk factors did not show a significant benefit from concomitant HT. PATIENT SUMMARY: We tested the impact of hormonal therapy (HT) duration during radiation therapy after radical prostatectomy. We identified three risk factors and observed a different impact of HT duration by clinical and pathologic characteristics. Patients with more adverse features benefit from long-term concomitant HT. On the contrary, for patients with a single risk factor, short-term HT may be reasonable. Patients without any risk factors did not show a significant benefit from concomitant HT.

Cigarette smoking is associated with adverse pathological response and increased disease recurrence amongst patients with muscle-invasive bladder cancer treated with cisplatin-based neoadjuvant chemotherapy and radical cystectomy: a single-centre experience.

OBJECTIVE: To investigate the association between smoking status and pathological response to cisplatin-based neoadjuvant chemotherapy (NAC) and survival outcomes in patients with muscle-invasive bladder cancer (MIBC) treated with radical cystectomy (RC). PATIENTS AND METHODS: We reviewed 201 patients treated with NAC and RC for cT2-cT4N0M0 BC between 01/1999 and 01/2015. Smoking status was categorised as: 'never', 'former', and 'current' smoker. Pathological response to NAC was defined as: complete (ypT0N0), partial (ypTis/Ta/T1, N0), and no response (ypT2-4 or ypN+). Clinicopathological characteristics were analysed according to smoking status. Logistic regression analyses tested the association between smoking status and pathological response to NAC. Cox regression analyses tested risk factors associated with recurrence, overall (OM) and cancer-specific mortality (CSM). RESULTS: Overall, there were 58 (28.9%) never smokers, 87 (43.3%) former smokers, and 56 (27.9%) current smokers. No response to NAC was more frequently noted in current smokers (73.2%; P = 0.007). Former smoker (odds ratio [OR] 2.28; P = 0.024) and current smoker statuses (OR 4.52; P < 0.001) were significantly associated with no response to NAC, after adjusting for age, gender, Charlson Comorbidity Index, and clinical stage. Similarly, current smoking status (hazard ratio [HR] 2.14; P = 0.03) and extravesical pathological tumour stage (HR 3.31; P < 0.001) were independently associated with an increased risk of recurrence after RC. CONCLUSION: Cigarette smoking was significantly associated with adverse pathological response to cisplatin-based NAC in patients with MIBC treated with RC. Current smokers were at significantly higher risk of disease recurrence as compared to former and never smokers.

Identifying the Optimal Candidate for Salvage Lymph Node Dissection for Nodal Recurrence of Prostate Cancer: Results from a Large, Multi-institutional Analysis.

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'sC 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.

Which Patients with Clinically Node-positive Prostate Cancer Should Be Considered for Radical Prostatectomy as Part of Multimodal Treatment? The Impact of Nodal Burden on Long-term Outcomes.

BACKGROUND: A role for local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies has been proposed. However, no data are available to identify men who would benefit from RP in this setting. OBJECTIVE: To identify predictors of clinical recurrence (CR) in surgically managed PCa patients with clinical lymphadenopathies. DESIGN, SETTING, AND PARTICIPANTS: We identified 162 patients with lymphadenopathies treated with RP and lymph node dissection at three referral centers. OUTCOME MEASURES AND STATISTICAL ANALYSES: CR was defined as the onset of metastases detected by conventional imaging. Kaplan-Maier analyses assessed time to CR after stratifying patients according to the site of lymphadenopathies and nodal burden. Regression tree analysis stratified patients into risk groups on the basis of their preoperative characteristics. RESULTS AND LIMITATIONS: Overall, 80% of patients had lymphadenopathies in the pelvis alone and 20% in the retroperitoneum±pelvis. The median size of positive nodes was 13mm. A total of 84 patients (52%) received neoadjuvant androgen deprivation therapy and 127 (78%) had pathological lymph node invasion. The median follow-up for survivors was 64 mo. The 8-yr CR-free and CSM-free survival rates were 59% and 80%, respectively. Biopsy grade group and preoperative nodal burden should identify patients more likely to experience CR. While <10% of men with biopsy grade group 1-3 and two or fewer clinical lymphadenopathies developed CR, up to 60% of patients with biopsy grade group 4-5 and retroperitoneal node involvement ultimately experienced CR at 8 yr after RP. The discrimination of the regression tree was 76% according to the area under the receiver operating characteristic curve. Our study is limited by potential unmeasured confounders and the relatively small sample size. CONCLUSIONS: Surgery in a multimodal setting might play a role in PCa patients with biopsy grade group 1-3 and/or enlarged nodes in the pelvis. Conversely, grade group 4-5 PCa and lymphadenopathies in the retroperitoneum are associated with worse oncologic outcomes. PATIENT SUMMARY: Approximately half of prostate cancer patients with clinical lymphadenopathies treated with radical prostatectomy are free from metastases at 8-yr follow-up. Radical prostatectomy with or without systemic therapies might play a role in selected patients with biopsy grade group 1-3 disease and/or enlarged nodes in the pelvis. Conversely, a higher grade group and the presence of lymphadenopathies in the retroperitoneum should identify candidates for systemic therapies upfront.