The Impact of Histological Variants on Oncological Outcomes After Surgical Resection of a Nonmetastatic Renal Cell Carcinoma with Tumor Thrombus: A Multi-institutional Study.

Background: There is no definitive evidence of the prognosis impact of histological variants (HVs) in patients who undergo surgical resection of a nonmetastatic renal cell carcinoma (nm-RCC) with venous tumor thrombus (TT). Objective: To investigate the impact of HVs on the prognosis of patients with nm-RCC with TT after radical surgery. Design setting and participants: Patients who underwent radical nephrectomy with the removal of the venous TT for an nm-RCC were included in a retrospective study. Outcome measurements and statistical analysis: Three groups were identified: clear cell (ccRCC), papillary (pRCC), and chromophobe (chRCC) RCC. The primary outcome measures (disease-free and overall survival [OS]) were assessed using the Kaplan-Meier method and compared using the log-rank test. Univariate and multivariate Cox proportional hazard models were used to study the impact of HVs on survival. Results and limitations: A total of 873 patients were included. The histological subtypes were distributed as follows: ccRCC in 780 cases, pRCC in 58 cases, and chRCC in 35 cases. At the time of data analysis, 612 patients were recurrence free and 228 had died. A survival analysis revealed significant differences in both OS and recurrence-free survival across histological subtypes, with the poorest outcomes observed in pRCC patients (p < 0.05). In a multivariable analysis, pRCC was independently associated with worse disease-free survival and OS (hazard ratio [HR]: 1.71; p = 0.01 and HR: 1.24; p = 0.04), while chRCC was associated with more favorable outcomes than ccRCC (HR: 0.05; p < 0.001 and HR: 0.02; p < 0.001). A limitation of the study is its retrospective nature. Conclusions: In this multicentric series, HVs appeared to impact the medium-term oncological prognosis of kidney cancer with TT. Patient summary: This study investigated the differences in oncological outcomes among histological variants (clear cell, papillary, and chromophobe) in a cohort of nonmetastatic renal cell carcinoma patients with venous tumor thrombus extension. We observed that these histological variants within this specific subgroup exhibit distinct outcomes, with papillary renal cell carcinoma being associated with the worst prognosis.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. MATERIALS AND METHODS: We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. RESULTS: Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI, highest ISUP grade in the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. CONCLUSION: In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

The Prognostic Role of Preoperative PSMA PET/CT in cN0M0 pN+ Prostate Cancer: A Multicenter Study.

CONTEXT: Despite negative preoperative conventional imaging, up to 10% of patients with prostate cancer (PCa) harbor lymph-node involvement (LNI) at radical prostatectomy (RP). The advent of more accurate imaging modalities such as PET/CT improved the detection of LNI. However, their clinical impact and prognostic value are still unclear. We aimed to investigate the prognostic value of preoperative PET/CT in patients node positive (pN+) at RP. EVIDENCE SYNTHESIS: We retrospectively identified cN0M0 patients at conventional imaging (CT and/or MRI, and bone scan) who had pN+ PCa at RP at 17 referral centers. Patients with cN+ at PSMA/Choline PET/CT but cN0M0 at conventional imaging were also included. Systemic progression/recurrence was the primary outcome; Cox proportional hazards models were used for multivariate analysis. EVIDENCE ACQUISITION: We included 1163 pN+ men out of whom 95 and 100 had preoperative PSMA and/or Choline PET/CT, respectively. ISUP grade ≥4 was detected in 66.6%. Overall, 42% of patients had postoperative PSA persistence (≥0.1 ng/mL). Postoperative management included initial observation (34%), ADT (22.7%) and adjuvant RT+/-ADT (42.8%). Median follow-up was 42 months. Patients with cN+ on PSMA PET/CT had an increased risk of systemic progression (52.9% vs. 13.6% cN0 PSMA PET/CT vs. 21.5% cN0 at conventional imaging; P < .01). This held true at multivariable analysis: (HR 6.184, 95% CI: 3.386-11-295; P < .001) whilst no significant results were highlighted for Choline PET/CT. No significant associations for both PET types were found for local progression, BCR, and overall mortality (all P > .05). Observation as an initial management strategy instead of adjuvant treatments was related with an increased risk of metastases (HR 1.808; 95% CI: 1.069-3.058; P < .05). CONCLUSIONS: PSMA PET/CT cN+ patients with negative conventional imaging have an increased risk of systemic progression after RP compared to their counterparts with cN0M0 disease both at conventional and/or molecular imaging.

Intratumoural immunotherapy plus focal thermal ablation for localized prostate cancer.

Major advances have been made in the use of immunotherapy for the treatment of solid tumours, including the use of intratumourally injected immunotherapy instead of systemically delivered immunotherapy. The success of immunotherapy in prostate cancer treatment has been limited to specific populations with advanced disease, which is thought to be a result of prostate cancer being an immunologically 'cold' cancer. Accordingly, combining intratumoural immunotherapy with other treatments that would increase the immunological heat of prostate cancer is of interest. Thermal ablation therapy is currently one of the main strategies used for the treatment of localized prostate cancer and it causes immunological activation against prostate tissue. The use of intratumoural immunotherapy as an adjunct to thermal ablation offers the potential to elicit a systemic and lasting adaptive immune response to cancer-specific antigens, leading to a synergistic effect of combination therapy. The combination of thermal ablation and immunotherapy is currently in the early stages of investigation for the treatment of multiple solid tumour types, and the potential for this combination therapy to also offer benefit to prostate cancer patients is exciting.

Nephrometry scores to predict oncological outcomes following partial nephrectomy (UroCCR Study 70).

PURPOSE: Partial nephrectomy (PN) for large or complex renal tumors can be difficult and associated with a higher risk of recurrence than radical nephrectomy. We aim to evaluate the clinical useful of nephrometry scores for predicting oncological outcomes in a large cohort of patients who underwent PN for renal cell carcinomas. METHODS: Our analysis included patients who underwent PN for renal cell carcinoma in 21 French academic centers (2010-2020). RENAL, PADUA, and SPARE scores were calculated based on preoperative imaging. Uni- and multivariate cox models were performed to identify predictors of recurrence-free survival and overall survival. The area under the curve (AUC) was used to identify models with the highest discrimination. Decision curve analyses (DCAs) determined the net benefit associated with their use. RESULTS: A total of 1927 patients were analyzed with a median follow-up of 32 months (14-45). RENAL score (p = 0.01), age (p = 0.002), histological type (p = 0.001), high nuclear grade (p = 0.001), necrotic component (p < 0.001), and positive margins (p = 0.005) were significantly related to recurrence in multivariate analyses. The discriminative performance of the 3 radiological scores was modest (65, 63, and 63%, respectively). All 3 scores showed good calibration, which, however, deteriorated with time. Decision curve analysis of the three models for the prediction of overall and recurrence-free survival was similar for all three scores and of limited clinical relevance. CONCLUSION: The association between nephrometry scores and oncological outcomes after NP is very weak. The use of these scores for predicting oncological outcomes in routine practice is therefore of limited clinical value.

Fascin-1 expression is associated with neuroendocrine prostate cancer and directly suppressed by androgen receptor.

BACKGROUND: Neuroendocrine prostate cancer (NEPC) is an aggressive form of prostate cancer, arising from resistance to androgen-deprivation therapies. However, the molecular mechanisms associated with NEPC development and invasiveness are still poorly understood. Here we investigated the expression and functional significance of Fascin-1 (FSCN1), a pro-metastasis actin-bundling protein associated with poor prognosis of several cancers, in neuroendocrine differentiation of prostate cancer. METHODS: Differential expression analyses using Genome Expression Omnibus (GEO) database, clinical samples and cell lines were performed. Androgen or antagonist's cellular treatments and knockdown experiments were used to detect changes in cell morphology, molecular markers, migration properties and in vivo tumour growth. Chromatin immunoprecipitation-sequencing (ChIP-Seq) data and ChIP assays were analysed to decipher androgen receptor (AR) binding. RESULTS: We demonstrated that FSCN1 is upregulated during neuroendocrine differentiation of prostate cancer in vitro, leading to phenotypic changes and NEPC marker expression. In human prostate cancer samples, FSCN1 expression is restricted to NEPC tumours. We showed that the androgen-activated AR downregulates FSCN1 expression and works as a transcriptional repressor to directly suppress FSCN1 expression. AR antagonists alleviate this repression. In addition, FSCN1 silencing further impairs in vivo tumour growth. CONCLUSION: Collectively, our findings identify FSCN1 as an AR-repressed gene. Particularly, it is involved in NEPC aggressiveness. Our results provide the rationale for the future clinical development of FSCN1 inhibitors in NEPC patients.

The impact of a second MRI and re-biopsy in patients with initial negative mpMRI-targeted and systematic biopsy for PIRADS ≥ 3 lesions.

OBJECTIVE: To evaluate the proportions of detected prostate cancer (PCa) and clinically significant PCa (csPCa), as well as identify clinical predictors of PCa, in patients with PI-RADS > = 3 lesion at mpMRI and initial negative targeted and systematic biopsy (initial biopsy) who underwent a second MRI and a re-biopsy. METHODS: A total of 290 patients from 10 tertiary referral centers were included. The primary outcome measures were the presence of PCa and csPCa at re-biopsy. Logistic regression analyses were performed to evaluate predictors of PCa and csPCa, adjusting for relevant covariates. RESULTS: Forty-two percentage of patients exhibited the presence of a new lesion. Furthermore, at the second MRI, patients showed stable, upgrading, and downgrading PI-RADS lesions in 42%, 39%, and 19%, respectively. The interval from the initial to repeated mpMRI and from the initial to repeated biopsy was 16 mo (IQR 12-20) and 18 mo (IQR 12-21), respectively. One hundred and eight patients (37.2%) were diagnosed with PCa and 74 (25.5%) with csPCa at re-biopsy. The presence of ASAP on the initial biopsy strongly predicted the presence of PCa and csPCa at re-biopsy. Furthermore, PI-RADS scores at the first and second MRI and a higher number of systematic biopsy cores at first and second biopsy were independent predictors of the presence of PCa and csPCa. Selection bias cannot be ruled out. CONCLUSIONS: Persistent PI-RADS ≥ 3 at the second MRI is suggestive of the presence of a not negligible proportion of csPca. These findings contribute to the refinement of risk stratification for men with initial negative MRI-TBx.

Can Simplified PADUA Renal (SPARE) Nephrometry scoring system help predict renal function outcomes after robot-assisted partial nephrectomy? (UroCCR study 93).

BACKGROUND: The SPARE Nephrometry Score (NS) is described as easier to implement than the RENAL and PADUA NSs, currently more widely used. Our objective was to compare the accuracy of SPARE NS in predicting renal function outcomes following RAPN. METHODS: A multicentric retrospective study was conducted using French kidney cancer network (UroCCR, NCT03293563) database. All patients included had RAPN for cT1 renal tumors between May 2010 and March 2021. SPARE was compared to RENAL, PADUA and Tumor Size to predict postoperative acute kidney injury (AKI), chronic kidney disease (CKD) upstaging, de novo CKD at 3-6 months follow-up and Trifecta failure. The ability of the different NSs and tumor size to predict renal function outcomes was evaluated using uni- and multivariate logistic regression models. RESULTS: According to our study criteria, 1171 patients were included. Mean preoperative tumor size and estimated glomerular filtration rate (eGFR) were 3.4±1.4 cm and 85.8 mL/min/1.73 m2. In total, 266 (22.7%), 87 (7.4%), 94 (8%), and 624 (53.3%) patients had AKI, de novo CKD, CKD upstaging, and Trifecta failure, respectively. In multivariate analysis, all three NSs and tumor size were independent predictors of AKI, CKD de novo, CKD upgrade and Trifecta failure. There was no significant difference between all three NS and tumor sizes in predicting renal function outcomes. CONCLUSIONS: SPARE Score seems to be a valid alternative to predict renal function outcomes after RAPN. Nevertheless, in our study, tumor size was as accurate as NSs in predicting postoperative outcomes and, therefore, seems to be the logical choice for surgical decisions.

Clinical trial protocol for P-NeLoP: a randomized controlled trial comparing the feasibility and outcomes of robot-assisted partial nephrectomy with low insufflation pressure using AirSeal versus standard insufflation pressure (UroCCR no. 85 study).

Robot-assisted partial nephrectomy (RAPN) is the standard of care for small, localized kidney tumors. This surgery is conducted within a short hospital stay and can even be performed as outpatient surgery in selected patients. In order to allow early rehabilitation of patients, an optimal control of postoperative pain is necessary. High-pressure pneumoperitoneum during surgery seems to be the source of significant pain during the first hours postoperatively. Our study is a prospective, randomized, multicenter, controlled study which aims to compare post-operative pain at 24 h between patients undergoing RAPN at low insufflation pressure (7 mmHg) and those operated on at standard pressure (12 mmHg) using the AirSeal system.This trial is registered in the US National Library of Medicine Trial Registry (NCT number: NCT05404685).

Late complications and 5 years outcomes of robotic partial nephrectomy in France: prospective assessment in the French Kidney Cancer Research Network (UroCCR 10).

PURPOSE: To describe the practice of robotic-assisted partial nephrectomy (RAPN) in France and prospectively assess the late complications and long-term outcomes. METHODS: Prospective, multicenter (n = 16), observational study including all patients diagnosed with a renal tumor who underwent RAPN. Preoperative, intraoperative, postoperative, and follow-up data were collected and stored in the French research network for kidney cancer database (UroCCR). Patients were included over a period of 12 months, then followed for 5 years. RESULTS: In total, 466 patients were included, representing 472 RAPN. The mean tumor size was 3.4 ± 1.7 cm, most of moderate complexity (median PADUA and RENAL scores of 8 [7-10] and 7 [5-9]). Indication for nephron-sparing surgery was relative in 7.1% of cases and imperative in 11.8%. Intraoperative complications occurred in 6.8% of patients and 4.2% of RAPN had to be converted to open surgery. Severe postoperative complications were experienced in 2.3% of patients and late complications in 48 patients (10.3%), mostly within the first 3 months and mainly comprising vascular, infectious, or parietal complications. At 5 years, 29 patients (6.2%) had chronic kidney disease upstaging, 21 (4.5%) were diagnosed with local recurrence, eight (1.7%) with contralateral recurrence, 25 (5.4%) with metastatic progression, and 10 (2.1%) died of the disease. CONCLUSION: Our results reflect the contemporary practice of French expert centers and is, to our knowledge, the first to provide prospective data on late complications associated with RAPN. We have shown that RAPN provides good functional and oncologic outcomes while limiting short- and long-term morbidity. TRIAL REGISTRATION: NCT03292549.

Robot Partial Prostatectomy for Anterior Cancer: Long-term Functional and Oncological Outcomes at 7 Years.

Partial prostatectomy has been described as an alternative to focal ablation therapy for the management of localized low- to intermediate-risk prostate cancer. This report aims to describe the long-term outcomes in a series of 28 men (2000-2022) who underwent robotic-assisted anterior partial prostatectomy (APP) for anteriorly located tumors entirely or partially within the anterior fibromuscular stroma. The median follow-up is 7 yr (interquartile range [IQR]: 4.2-8). The median prostate-specific antigen (PSA) before APP was 9.6 (6-11). Continence remained uninterrupted in 92% of patients. Erectile function without drug remained uninterrupted in 69%. The median nadir PSA after APP was 0.36 ng/ml (IQR: 0.25-0.60). Cancer recurrence at biopsies at the margins of the primary cancer resected area in case of a PSA elevation was observed in eight patients and led to salvage completion robotic radical prostatectomy at a median time of 3.25 yr (IQR: 2.4-6). Freedom from post-APP cancer recurrence at 7 yr was 62.7% (35.0-81.3%). Pre-APP tumor volume at magnetic resonance imaging (MRI) and volume of grade 4/5 were predictive of recurrence. Freedom from biochemical recurrence after completion radical prostatectomy at 7 yr was 94.7% (68.1-99.3%). All 28 patients are alive. No one had systemic treatment or metastases. These results confirm our initial report of robotic APP with good functional results and acceptable oncological results. The use of the inclusion criteria of pre-APP tumor volume at MRI <3 cc may decrease the risk of recurrence. Patient summary: In this report, we looked at outcomes for infrequent cases of anterior prostate cancer treated with anterior partial prostatectomy, an uncommon surgical procedure as an alternative to in situ focal ablation therapy, to better preserve functional outcomes as compared with whole gland therapy. We found that functional outcomes of uninterrupted continence and erectile function were good. Out of 28 patients, eight had recurrence in the remaining prostate and were treated with a second surgical procedure, radical prostatectomy, which was feasible. We conclude that this new technique is feasible with good functional results and acceptable oncological results, which can be shared with the patients.

Minimally invasive nephron-sparing treatments for T1 renal cell cancer in patients over 75 years: a comparison of outcomes after robot-assisted partial nephrectomy and percutaneous ablation.

PURPOSE: To compare the oncological and perioperative outcomes of robot-assisted partial nephrectomy (RPN) and percutaneous thermal ablation (PTA) for treatment of T1 renal cell cancer (RCC) in patients older than 75 years. MATERIALS AND METHODS: Retrospective national multicenter study included all patients older than 75 years treated for a T1 RCC by RPN or PTA between January 2010 and January 2021. Patients' characteristics, tumor data, and perioperative and oncological outcomes were compared. RESULTS: A total of 205 patients for 209 procedures (143 RPN and 66 PTA) were included. In the PTA group, patients were older (80.4 ± 3.7 vs. 79 ± 3.7 years (p = 0.01)); frailer (ASA score (2.43 ± 0.6 vs. 2.17 ± 0.6 (p < 0.01)); and more frequently had a history of kidney surgery (16.7% [11/66] vs. 5.6% [8/143] (p = 0.01)) than in the RPN group. Tumors were larger in the RPN group (2.7 ± 0.7 vs. 3.2 ± 0.9 cm (p < 0.01)). Operation time, length of hospital stay, and increase of creatinine serum level were higher in RPN (respectively 92.1 ± 42.7 vs. 150.7 ± 61.3 min (p < 0.01); 1.7 ± 1.4 vs. 4.2 ± 3.4 days (p < 0.01); 1.9 ± 19.3% vs. 10.1 ± 23.7 (p = 0.03)). Disease-free survival and time to progression were similar (respectively, HR 2.2; 95% CI 0.88-5.5; p = 0.09; HR 2.1; 95% CI 0.86-5.2; p = 0.1). Overall survival was shorter for PTA that disappeared after Cox adjusting model (HR 3.3; 95% CI 0.87-12.72; p = 0.08). CONCLUSION: Similar oncological outcomes are observed after PTA and RPN for T1 RCC in elderly patients. CLINICAL RELEVANCE STATEMENT: Robot-assisted partial nephrectomy and percutaneous thermal ablation have similar oncological outcomes for T1a kidney cancer in patients over 75 years; however, operative time, decrease in renal function, and length of hospital stay were lower with ablation. KEY POINTS: • After adjusting model for age and ASA score, similar oncological outcomes are observed after percutaneous thermal ablation and robot-assisted partial nephrectomy for T1 renal cell cancer in elderly patients. • Operation time, length of hospital stay, and increase of creatinine serum level were higher in the robot-assisted partial nephrectomy group.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Is There an Impact of Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsy on the Risk of Upgrading in Final Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy? An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.

BACKGROUND: The concordance rates of transperineal (TP) versus transrectal (TR) prostate biopsies with radical prostatectomy (RP) specimen have been assessed poorly in men diagnosed with magnetic resonance imaging (MRI)-targeted biopsy (TBx). OBJECTIVE: To evaluate International Society of Urological Pathology (ISUP) concordance rates between the final pathology at RP and MRI-TBx or MRI-TBx + random biopsy (RB) according to the biopsy approach. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional database included patients diagnosed with TP or TR treated with RP. INTERVENTION: TP-TBx or TR-TBx of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The ISUP grade at biopsy was compared with the final pathology. A multivariable logistic regression analysis (MVA) was performed to assess the association between the biopsy approach (TP-TBx vs TR-TBx) and ISUP upgrading, downgrading, concordance, and clinically relevant increase (CRI). RESULTS AND LIMITATIONS: Overall, 752 (59%) versus 530 (41%) patients underwent TR versus TP. At the MVA, TP-TBx was an independent predictor of upgrading (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.9, p < 0.01) and improved concordance relative to the final pathology (OR 1.7, 95% CI 1.2-2.5, p < 0.01) after adjusting for age, cT stage, Prostate Imaging Reporting and Data System, number of targeted cores, prostate-specific antigen, and prostate volume. Moreover, TP-TBx was associated with a lower risk of CRI than TR-TBx (OR 0.7, p < 0.01). This held true when considering patients who underwent MRI-TBx + RB (OR 0.6, p < 0.01). The inclusion of men who had RP represents a potential selection bias. CONCLUSIONS: The adoption of TP-TBx compared with TR-TBx may reduce the risk of upgrading and improve the concordance of biopsy grade with the final pathology. The TP approach decreases the odds of CRI with improved patient selection for the correct active treatment. PATIENT SUMMARY: In this report, we evaluated whether transperineal (TP) targeted biopsy (TBx) may improve the concordance of clinically significant prostate cancer with the final pathology in comparison with transrectal (TR) TBx in a large worldwide population. We found that TP-TBx might increase concordance compared with TR-TBx. Adding random biopsies to target one increases accuracy; however, concordance with the final pathology is overall suboptimal even with the TP approach.

Metastatic Sites' Location and Impact on Patient Management After the Introduction of Prostate-specific Membrane Antigen Positron Emission Tomography in Newly Diagnosed and Biochemically Recurrent Prostate Cancer: A Critical Review.

CONTEXT: The introduction of prostate-specific membrane antigen positron emission tomography (PSMA-PET) had a substantial impact on the management of prostate cancer (PCa) patients with a stage migration phenomenon and consequent treatment changes. OBJECTIVE: To summarise the role of PSMA-PET to define the burden of disease through an accurate location of metastatic site(s) in PCa patients, describing the most common locations at PSMA-PET in the primary staging and recurrence setting, and to assess the clinical impact in the decision-making process. EVIDENCE ACQUISITION: A comprehensive nonsystematic literature review was performed in April 2022. Literature search was updated until March 2022. The most relevant studies have been summarised, giving priority to registered clinical trials and multicentre collaborations. EVIDENCE SYNTHESIS: PSMA-PET showed higher diagnostic accuracy than conventional imaging both in newly diagnosed PCa and in recurrent disease. This greater accuracy led to a migration of a higher proportion of patients identified with metastatic disease. Bone metastases were reported as the most frequent site of metastatic spread in staging (up to 17%) and restaging (up to 18%). In staging, considering the suboptimal sensitivity in lymph node metastasis detection prior to radical surgery, PSMA-PET should be performed in patients with high risk or unfavourable intermediate risk only, and it is not recommended to routinely avoid pelvic lymph node dissection in case of a negative scan. In case of prostate-specific antigen relapse, PSMA-PET had higher diagnostic accuracy than other diagnostic procedures in the early detection of the sites of recurrence, thus influencing the therapy decision-making process. CONCLUSIONS: PSMA-PET detects a higher number of lesions than conventional imaging or other PET radiotracers, especially metastatic lesions unseen with other modalities. The high diagnostic accuracy of PSMA-PET leads to a significant patient upstage and thus an impact in clinical management, even if the overall impact on cancer mortality is still to be assessed. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) identifies metastatic lesions with higher accuracy than conventional imaging, both in primary prostate cancer and during disease recurrence. Skeletal metastasis and extrapelvic lymph nodes are the most common sites of metastatic spread. The high accuracy of PSMA-PET in the detection of metastatic disease led to a significant impact on patient management, even if the overall impact on cancer mortality is still to be assessed.

The Changing Face of cN0M0 Prostate Cancer Being Found With pN+ After Surgery in the Contemporary Era: Results of an International European Survey on Disease Management.

INTRODUCTION: The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community. METHODS: Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. RESULTS: We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05). CONCLUSIONS: The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered.

Association between cannabis use with urological cancers: A population-based cohort study and a mendelian randomization study in the UK biobank.

BACKGROUND: Legislation of cannabis use has been approved in many European and North American countries. Its impact on urological cancers is unclear. This study was conducted to explore the association between cannabis use and the risk of urological cancers. METHODS: We identified 151,945 individuals with information on cannabis use in the UK Biobank from 2006 to 2010. Crude and age-standardized incidence ratios of different urological cancers were evaluated in the entire cohort and subgroups. Cox regression was performed for survival analysis. RESULTS: Previous use of cannabis was a significant protective factor for renal cell carcinoma (HR = 0.61, 95%CI:0.40-0.93, p = 0.021) and prostate cancer (HR = 0.82, 95%CI:0.73-0.93, p = 0.002) in multivariable analysis. The association between previous cannabis use and both renal cell carcinoma and bladder cancer was only observed in females (HRRCC  = 0.42, 95%CI:0.19-0.94, p = 0.034; HRBCa  = 0.43, 95%CI:0.21-0.86, p = 0.018) but not in men. There was no significant association between cannabis use and testicular cancer incidence. Mendelian randomization demonstrated a potential causal effect of cannabis use on a lower incidence of renal cell carcinoma. CONCLUSIONS: Previous use of cannabis was associated with a lower risk of bladder cancer, renal cell carcinoma, and prostate cancer. The inverse association between cannabis and both renal cell carcinoma and bladder cancer was only found in females but not in males.