Variability of mpMRI diagnostic performance according to the upfront individual patient risk of having clinically significant prostate cancer.

BACKGROUND: To assess the variation of multiparametric magnetic resonance imaging (mpMRI) positive predictive value (PPV) according to each patient's risk of clinically significant prostate cancer (csPCa) based exclusively on clinical factors. METHODS: We evaluated 999 patients with positive mpMRI (PI-RADS ≥ 3) receiving targeted (TBx) plus systematic prostate biopsy. We built a multivariable logistic regression analysis (MVA) using clinical risk factors to calculate the individual patients' risk of harboring csPCa at TBx. A second MVA tested the association between individual patients' clinical risk and mpMRI PPV accounting for the PI-RADS score. Finally, we plotted the PPV of each PI-RADS score by the individual patient pretest probability of csPCa using a LOWESS approach. RESULTS: Overall, TBx found csPCa in 21%, 51%, and 80% of patients with PI-RADS 3, 4, and 5 lesions, respectively. At MVA, age, PSA, digital rectal examination (DRE), and prostate volume were significantly associated with the risk of csPCa at biopsy. DRE yielded the highest odds ratio (OR: 2.88; p < 0.001). The individual patient's clinical risk was significantly associated with mpMRI PPV (OR: 2.49; p < 0.001) using MVA. Plotting the mpMRI PPV according to the predicted clinical risks, we observed that for patients with clinical risk close to 0 versus patients with risk higher than 90%, the mpMRI PPV of PI-RADS 3, 4, and 5 ranged from 0% to 75%, from 0% to 96%, and from 45% to 100%, respectively. CONCLUSION: mpMRI PPV varies according to the individual pretest patient's risk based on clinical factors. These findings should be considered in the decision-making process for patients with suspect MRI findings referred for a prostate biopsy. Moreover, our data support the need for further studies to create an individualized risk prediction tool.

Defining the optimal target-to-background ratio to identify positive lymph nodes in prostate cancer patients undergoing robot-assisted [99mTc]Tc-PSMA radioguided surgery: updated results and ad interim analyses of a prospective phase II study.

INTRODUCTION: Prostate-specific membrane antigen radioguided surgery (PSMA-RGS) might identify lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing extended pelvic lymph node dissection (ePLND). The optimal target-to-background (TtB) ratio to define RGS positivity is still unknown. MATERIALS & METHODS: Ad interim analyses which focused on 30 patients with available pathological information were conducted. All patients underwent preoperative PSMA positron emission tomography (PET). 99m-Technetium-PSMA imaging and surgery ([99mTc]Tc-PSMA-I&S) was administered the day before surgery. In vivo measurements were conducted using an intraoperative gamma probe. Performance characteristics and implications associated with different TtB ratios were assessed. RESULTS: Overall, 9 (30%) patients had LNI, with 22 (13%) and 80 (11%) positive regions and lymph nodes, respectively. PSMA-RGS showed uptakes in 12 (40%) vs. 7 (23%) vs. 6 (20%) patients for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4. At a per-region level, sensitivity, specificity and accuracy for a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4 were 72%, 88% and 87% vs. 54%, 98% and 92% vs. 36%, 99% and 91%. Performing ePLND only in patients with suspicious spots at PSMA PET (n = 7) would have spared 77% ePLNDs at the cost of missing 13% (n = 3) pN1 patients. A TtB ratio ≥ 2 at RGS identified 8 (24%) suspicious areas not detected by PSMA PET, of these 5 (63%) harbored LNI, with one pN1 patient (11%) that would have been missed by PSMA PET. Adoption of a TtB ratio ≥ 2 vs. ≥ 3 vs. ≥ 4, would have allowed to spare 18 (60%) vs. 23 (77%) vs. 24 (80%) ePLNDs missing 2 (11%) vs. 3 (13%) vs. 4 (17%) pN1 patients. CONCLUSIONS: PSMA-RGS using a TtB ratio ≥ 2 to identify suspicious nodes, could allow to spare > 50% ePLNDs and would identify additional pN1 patients compared to PSMA PET and higher TtB ratios.

Trimodal therapy effect on survival in urothelial vs non-urothelial bladder cancer.

OBJECTIVE: To address cancer-specific mortality free-survival (CSM-FS) differences in patients with urothelial carcinoma of the urinary bladder (UCUB) vs non-UCUB who underwent trimodal therapy (TMT), according to organ confined (OC: T2N0M0) vs non-organ confined (NOC: T3-4NanyM0 or TanyN1-3M0) clinical stages. PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2020), we identified patients with cT2-T4N0-N3M0 bladder cancer treated with TMT, defined as the combination of transurethral resection of bladder tumour, chemotherapy, and radiotherapy. Temporal trends described TMT use over time. Kaplan-Meier plots and multivariable Cox regression (MCR) models addressed CSM in UCUB vs non-UCUB according to OC vs NOC stages. RESULTS: Of 5130 assessable TMT-treated patients, 425 (8%) harboured non-UCUB vs 4705 (92%) who had UCUB. The TMT rates increased for patients with OC UCUB from 92.4% to 96.8% (estimated annual percentage change of 0.4%, P < 0.001), but not in the NOC stages (P = 0.3). In the OC stage, the median CSM-FS was 36 months in patients with non-UCUB vs 60 months in those with UCUB, respectively (P = 0.01). Conversely, in the NOC stage, the median CSM-FS was 23 months both in UCUB and non-UCUB (P = 0.9). In the MCR models addressing OC stage, non-UCUB histology independently predicted higher CSM (hazard ratio 1.45, P = 0.004), but not in the NOC stage (P = 0.9). CONCLUSION: In OC UCUB, TMT rates have increased over time in a guideline-consistent fashion. Patients with OC non-UCUB treated with TMT showed a CSM disadvantage relative to OC UCUB. In the NOC stage, use of TMT resulted in dismal CSM, regardless of UCUB vs non-UCUB histology.

Peri- and post-operative outcomes of robot-assisted radical cystectomy after the implementation of the EAU guidelines recommendations for collecting and reporting complications at a high-volume referral center.

PURPOSE: No studies relied on a standardized methodology to collect postoperative complications after robot-assisted radical cystectomy (RARC). The aim of our study was to evaluate peri- and post-operative outcomes of patients undergoing RARC adhering to the European Association of Urology (EAU) recommendations for reporting surgical outcomes and using a long postoperative follow-up. MATERIALS AND METHODS: 246 patients who underwent RARC with intracorporal urinary diversion at a single tertiary referral center with a postoperative follow-up ≥ 1 year for survivors. Postoperative outcomes were collected prospectively by interviews done by medical doctors. Complications were scored using the Clavien-Dindo classification (CD), grouped by type and severity (severe: CD score ≥ 3). We described peri- and post-operative outcomes and complication chronological distribution. RESULTS: Overall, 16 (6.5%) and 225 patients (91%) experienced intraoperative and postoperative complications, respectively. Moreover, 139 (57%) experienced severe complications. The most common any-grade and severe complications were infectious (72%) and genitourinary (35%), respectively. Overall, 52% of complications (358/682) occurred within 10 days from surgery, and 51% of severe complications (106/207) occurred within 35 days. However, 13% of complications (90/682) and 28% of severe complications (59/207) occurred 3 months after surgery. The earliest complications were fever of unknown origins and paralytic ileus (median time-to-complication [mTTC]: 4 days), the latest complications were urinary tract infection (mTTC: 40 days) and hydronephrosis/ureteral obstruction (mTTC: 70 days). CONCLUSIONS: The rate of postoperative complications after RARC is > 90% when a standardized collection method and a long follow-up is implemented. These results should be used to identify potential areas of improvement and for preoperative patient counseling.

Is MRI ready to replace biopsy during active surveillance?

Active surveillance (AS) is a conservative management option recommended for patients diagnosed with low-risk prostate cancer (PCa) and selected cases with intermediate-risk PCa. The adoption of prostate MRI in the primary diagnostic setting has sparked interest in its application during AS. This review aims to examine the role and performance of multiparametric MRI (mpMRI) across the entire AS pathway, from initial stratification to follow-up, also relative to the utilization of the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) criteria. Given the high negative predictive value of mpMRI in detecting clinically significant PCa (csPCa), robust evidence supports its use in patient selection and risk stratification at the time of diagnosis or confirmatory biopsy. However, conflicting results have been observed when using MRI in evaluating disease progression during follow-up. Key areas requiring clarification include addressing the clinical significance of MRI-negative csPCa, optimizing MRI quality, determining the role of biparametric MRI (bpMRI) or mpMRI protocols, and integrating artificial intelligence (AI) for improved performance. CLINICAL RELEVANCE STATEMENT: MRI plays an essential role in the selection, stratification, and follow up of patients in active surveillance (AS) for prostate cancer. However, owing to existing limitations, it cannot fully replace biopsies in the context of AS. KEY POINTS: Multiparametric MRI (mpMRI) has become a crucial tool in active surveillance (AS) for prostate cancer (PCa). Conflicting results have been observed regarding multiparametric MRI efficacy in assessing disease progression. Standardizing MRI-guided protocols will be critical in addressing current limitations in active surveillance for prostate cancer.

Identifying low cancer-specific mortality risk lymph node-positive radical prostatectomy patients.

OBJECTIVES: To identify low cancer-specific mortality (CSM) risk lymph node-positive (pN1) radical prostatectomy (RP) patients. METHODS: Within Surveillance, Epidemiology and End Results database (2010-2015) pN1 RP patients were identified. Kaplan-Meier plots and multivariable Cox-regression (MCR) models were used. Pathological characteristics were used to identify patients at lowest CSM risk. RESULTS: Overall, 2197 pN1 RP patients were identified. Overall, 5-year cancer-specific survival (CSS) rate was 93.3%. In MCR models ISUP GG1-2 (hazard ratio [HR]: 0.12, p < 0.001), GG3 (HR: 0.14, p < 0.001), GG4 (HR: 0.35, p = 0.002), pT2 (HR: 0.27, p = 0.012), pT3a (HR: 0.28, p = 0.003), pT3b (HR: 0.39, p = 0.009), and 1-2 positive lymph nodes (HR: 0.64, p = 0.04) independently predicted lower CSM. Pathological characteristics subgroups with the most protective hazard ratios were used to identify low-risk (ISUP GG1-3 and pT2-3a and 1-2 positive lymph nodes) patients versus others (ISUP GG4-5 or pT3b-4 or ≥3 positive lymph nodes). In Kaplan-Meier analyses, 5-year CSS rates were 99.3% for low-risk (n = 480, 21.8%) versus 91.8% (p < 0.001) for others (n = 1717, 78.2%). CONCLUSIONS: Lymph node-positive RP patients exhibit variable CSS rates. Within this heterogeneous group, those at very low risk of CSM may be identified based on pathological characteristics, namely ISUP GG1-3, pT2-3a, and 1-2 positive lymph nodes. Such stratification scheme might be of value for individual patients counseling, as well as in design of clinical trials.

Survival outcomes of patients treated with local therapy for nonmetastatic prostate cancer with high prostate-specific antigen concentrations.

BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

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.

Focal therapy for primary tumor and metastases in de novo or recurrent oligometastatic prostate cancer: current standing and future perspectives.

PURPOSE: Focal therapy (FT) is gaining increasing acceptance in the management of localized prostate cancer particularly due to its favorable safety. Preliminary evidence suggests advantageous utilization of local treatment in the field of oligometastatic prostate cancer (OMPC). Since data on the utilization of FT in OMPC are scarce, we sought to summarize available evidence. METHODS: For this narrative comprehensive review, we employed PubMed®, Web of Science™, Embase®, Scopus®, and clinicaltrial.gov databases and Google web search engine to seek peer-reviewed articles, published abstracts from international congresses, and ongoing trials in the English language using the terms "prostate cancer", "oligometastatic", "hormone-sensitive", "focal therapy", "focal treatment", "cryotherapy", "ablation", "cancer" as well as "metastasis-directed therapy. We focused on relevant publications on FT utilized in OMPC targeting the primary or metastatic sites as well as completed and ongoing clinical trials. RESULTS: Growing evidence points to distinct differences in the biologic behavior and molecular signaling processes of OMPC as compared to polymetastatic disease (PMPC). No established biomarkers are available to accurately identify OMPC yet, while several candidates are currently under investigation. The evolution of molecular imaging is set to aid in selecting patients benefitting most from local management. Differences between OMPC and PMPC should be considered when designing the optimal therapeutic strategy. While efficacy data for FT in comparison to standard care in OMPC are scarce, longer progression-free survival and time to castration resistance have been demonstrated for bone metastatic prostate cancer with the primary tumor treated by cryosurgery followed by androgen deprivation therapy (ADT) compared to ADT alone. CONCLUSION: Ongoing research efforts are eagerly awaited to better characterize OMPC and establish customized strategies for patients with this condition.

Magnetic resonance imaging (MRI) for local staging before salvage radical prostatectomy: a meta-analysis.

PURPOSE: The reliability of magnetic resonance imaging (MRI) as a local and nodal staging tool in radio-recurrent prostate cancer (PCa) is still unclear. The present study aims at evaluating the predictive value of MRI in the detection of extracapsular extension (ECE), seminal vesical invasion (SVI) and nodal involvement (LNI) in patients after primary radio (EBRT) and/or brachytherapy (BT) before salvage radical prostatectomy (SRP). METHODS: This systematic review and meta-analysis were performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pubmed, Scopus, and Web of Science databases were systemically reviewed to extract the data on diagnostic performance of MRI in radio-recurrent PCa. RESULTS: Four studies comprising 94 radio-recurrent PCa patients were included. The pooled prevalence of ECE, SVI, and LNI was 61%, 41%, and 20%, respectively. The pooled sensitivity for ECE, SVI and LNI detection was 53% (CI 95% 19.8-83.6%), 53% (CI 95% 37.2-68%) and 33% (CI 95% 4.7-83.1%) respectively, whereas specificity was 75% (CI 95% 40.6-92.6%), 88% (CI 95% 71.7-95.9%) and 92% (CI 95% 79.6-96.8%). The sensitivity analysis revealed that a single outlying study using only T2-weighted imaging instead of multiparametric MRI reported significantly higher sensitivity with significantly lower specificity. CONCLUSIONS: This is the first meta-analysis reporting reliability of staging MRI in a radio-recurrent setting. MRI provides poor sensitivity while maintaining high specificity for local and nodal staging before SRP. However, current evidence is limited to the low number of heterogenous studies at meaningful risk of bias.

Oncological and perioperative outcomes of surgery with or without metastasis-directed therapy as part of a multimodal treatment in men with de-novo oligometastatic prostate cancer.

PURPOSE: To investigate the feasibility, safety, and oncological outcomes of Radical Prostatectomy (RP; either Robot-Assisted [RARP] or Open RP [ORP]) in oligometastatic prostate cancer (omPCa). Additionally, we assessed whether there was an added benefit of metastasis-directed therapy (MDT) in these patients in the adjuvant setting. METHODS: Overall, 68 patients with omPCa (≤ 5 skeletal lesions at conventional imaging) treated with RP and pelvic lymph node dissection between 2006 and 2022 were included. Additional therapies (androgen deprivation therapy [ADT] and MDT) were administered according to the treating physicians' judgment. MDT was defined as metastasis surgery/radiotherapy within 6 months of RP. We assessed Clinical Progression (CP), Biochemical Recurrence (BCR), post-operative complications and overall mortality (OM) of RP and the impact of adjuvant MDT + ADT versus RP + ADT alone. RESULTS: Median follow-up was 73 months (IQR 62-89). RARP reduced the risk of severe complications after adjusting for age and CCI (OR 0.15; p = 0.02). After RP, 68% patients were continent. Median 90-days PSA after RP was 0.12 ng/dL. CP and OM-free survival at 7 years were 50% and 79%, respectively. The 7-years OM-free survival rates were 93 vs. 75% for men treated with vs. without MDT (p = 0.04). At regression analyses, MDT after surgery was associated with a 70% decreased mortality rate (HR 0.27, p = 0.04). CONCLUSIONS: RP appeared to represent a safe and feasible option in omPCa. RARP reduced the risk of severe complications. Integrating MDT with surgery in the context of a multimodal treatment might improve survival in selected omPCa patients.

Impact of prostate MRI central review over the diagnostic performance of MRI-targeted biopsy: should we routinely ask for an expert second opinion?

PURPOSE: There is substantial variability in multiparametric MRI (mpMRI) protocols and inter-readers' agreement. We tested the effect of a central mpMRI review on the detection of clinically significant PCa (csPCa) in a tertiary referral center. METHODS: We retrospectively analyzed a cohort of 364 consecutive men with a positive externally performed mpMRI (PI-RADS ≥ 3) who underwent a targeted biopsy (TBx) plus a systematic biopsy at a single tertiary referral center (2018-2020). Of those mpMRIs, 32% (n = 116) were centrally reviewed. We compared the detection of csPCa between the non-central-reviewed vs reviewed group. Multivariable logistic regression models (MVA) tested the relationship between mpMRI central review and the detection of csPCa at TBx. RESULTS: The detection of csPCa at TBx in non-central-reviewed vs central-reviewed group was 41 vs 63%, respectively (p = 0.001). The distribution of PI-RADS 2, 3, 4, and 5 at initial assessment vs after mpMRI central review was 0, 37, 47, and 16% vs 39, 9, 35, and 16%, respectively (p < 0.004). Of 43 patients with initial PI-RADS 3 score, respectively 67, 21, and 12, and 0% had a revised PI-RADS score of ≤ 2, 3, 4, and 5. At MVA, mpMRI central review (OR: 1.65, CI 0.85-0.98) was significantly associated with higher csPCa detection at TBx. CONCLUSIONS: We demonstrated that a central review of external mpMRIs may decrease the overcall of equivocal lesions, namely PI-RADS 3, and should be considered to maximize the clinical benefit of TBx in terms of increasing the detection of csPCa and eventually decreasing the rate of unnecessary biopsies.

Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis.

INTRODUCTION: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. METHODS: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. RESULTS: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2-8.7) years and 5.7 (IQR 4.8-8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). CONCLUSIONS: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup.

Risk and predictors of adverse pathology after radical prostatectomy in patients diagnosed with IUSP 1-2 prostate cancer at MRI-targeted biopsy: a multicenter analysis.

PURPOSE: Although active surveillance (AS) is recommended for low- to favorable intermediate-risk prostate cancer (PCa), risk of upgrading at radical prostatectomy (RP) is not negligible. Available studies based on systematic transrectal ultrasound biopsy might not be applicable to contemporary cohorts diagnosed with MRI-targeted biopsy (TB). The aim of the present study is to explore rates and risk factors for adverse outcomes (AO) at RP in patients with ISUP ≤ 2 PCa detected at TB with concomitant systematic biopsy (SB). METHODS: Multicenter, retrospective analysis of 475 consecutive patients with ISUP ≤ 2 PCa at MRI-TB + SB is treated with RP. AO were defined as ISUP upgrading, adverse pathology (upgrading to ISUP ≥ 3 and/or ≥ pT3 at RP, and/or pN1) (AP) or biochemical recurrence (BCR) in men with follow-up (n = 327). RESULTS: The rate of ISUP upgrading, upgrading ≥ 3, and AP were 39%, 21%, and 43%. Compared to ISUP2, men with ISUP1 PCa had a higher rate of overall upgrading (27 vs. 67%, p < 0.001), but less upgrading to ≥ 3 (27 vs. 10%, p < 0.001). AP was more common when ISUP2 was detected with a combined MRI-TB + SB approach compared to considering TB (p = 0.02) or SB (p = 0.01) alone. PSA, PSA density, PI-RADS, ISUP at TB, overall biopsy ISUP and EAU classification were predictors of upgrading to ISUP ≥ 3 and AP. The 1 year BCR-free survival was 94% with no differences in BCR rates between subgroups. CONCLUSION: Upgrading in ISUP ≤ 2 PCa remains prevalent even in men diagnosed in the MRI era. The use of MRI-TB with concomitant SB allows for the accurate identification of ISUP2 PCa and predicts the risk of AO at RP.

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.

Optimal combination therapy for metastatic hormone-sensitive prostate cancer: new evidence, challenges and unanswered questions.

PURPOSE OF REVIEW: To evaluate the evidence supporting treatment intensification in mHSPC, with a focus on possible indications for treatment in each clinical setting. RECENT FINDINGS: There is a growing armamentarium of treatment options for patients with metastatic hormone-sensitive prostate cancer (mHSPC). These include combinations of treatments such as androgen deprivation therapy (ADT), docetaxel, and new antiandrogenic therapies. Treatment intensification with chemotherapy or newer hormonal agents may improve patient's oncologic outcomes, but it can also come with additional toxicities and costs. Therefore, we need to take into account individual patient factors and preferences when deciding on the optimal combination therapy. Additionally, ongoing research is needed to identify biomarkers and new image techniques that can predict response to treatment and identify the best candidate for each treatment. SUMMARY: Challenges and unanswered questions regarding treatment intensification and de-intensification are still present. Further studies are still needed to identify which patients would benefit most from this approach to improve quality of life without compromising overall survival outcomes.

Urinary continence in high-risk prostate cancer after robot-assisted radical prostatectomy.

PURPOSE OF REVIEW: Urinary incontinence is common postoperative complication following robot-assisted radical prostatectomy (RARP) in patients with prostate cancer (PCa). Despite the increasing adoption of RARP in the treatment of high-risk PCa (HRPC), concerns persist regarding the adequacy of reported continence outcomes in this subgroup. This review aims to illuminate the state of continence recovery in HRPC patients post-RARP. RECENT FINDINGS: Urinary continence (UC) recovery rates in HRPC was reported to be lower than the intermediate/low-risk counterparts from 6 to 24 months post-RARP. Predictive models showed that age, obesity, race, disease status, and surgical approaches represent predictors of continence recovery. Special techniques like NeuroSAFE technique and Retzius-Sparing approach also play a role in reducing incontinence also in the high-risk scenario. SUMMARY: RARP for HRPC appears to be associated with worse continence compared with other risk groups. A multimodality approach for prediction and prevention of incontinence after RARP is vital. Further research into this area is necessary to enhance continence recovery outcomes in HRPC patients undergoing RARP.

Salvage lymphadenectomy after primary therapy with curative intent for prostate cancer.

PURPOSE OF REVIEW: To provide a summary of the current literature on salvage lymph node dissection (sLND) in patients with nodal recurrent prostate cancer (PCa) with focus on imaging, the extent of sLND and oncologic outcomes. RECENT FINDINGS: The clinical practice guidelines recommend performing PET/CT in patients with biochemical recurrence (BCR) after primary therapy. PSMA PET/CT has demonstrated superiority over choline PET/CT and MRI, especially at low prostate-specific antigen (PSA) levels. Although the heterogeneity in available literature does not allow standardization of surgical templates for sLND and PET/CT scan can guide the extent of surgical dissection, an anatomically defined extended template is typically considered. Radio-guided surgery (RGS) suggests an improved positive lymph node yield compared with standard sLND. However, long-term data are needed to evaluate the oncologic impact of sLND. The main aims of sLND are to delay recurrence and to postpone the need for systemic therapy. Available evidence suggests that around 40-80% of men can achieve complete biochemical response after sLND and 10-30% remain BCR free after 5 years. Robotic sLND might represent an option to reduce the risk of complications without compromising oncological outcomes; validation in controlled prospective studies is, however, needed. SUMMARY: sLND is a valid treatment option for patients with nodal recurrence only after primary therapy for PCa. Further optimization of patient selection based on highly sensitive and specific imaging and clinical factors remains an unmet need. To maximize the benefit of this approach, sLND should be discussed with patients who harbor lymph node-only recurrence after primary therapy in a shared decision-making.

The role of nuclear medicine tracers for prostate cancer surgery: from preoperative to intraoperative setting.

PURPOSE OF REVIEW: There has been a growing interest in the use of novel molecular imaging modalities for the management of prostate cancer (PCa), spanning from diagnostic to therapeutic settings. The aim of this review is to provide a comprehensive overview of recently published studies investigating the use of novel nuclear medicine tracers across different stages of PCa management. RECENT FINDINGS: Emerging evidence supports the use of molecular imaging for preoperative staging of PCa, where prostate-specific membrane antigen (PSMA) PET has shown superior accuracy compared to conventional imaging for the detection of nodal and distant metastases, which needs to be translated to new risk stratification. A role for PSMA PET has been proposed for PCa diagnosis, with local activity associated with histology. Surgical guidance, using either visual feedback or gamma-ray detectors to identify tissues with accumulated radio-labeled tracers, may improve the ability to resect locoregional diseases and thus maximize oncological control. PSMA targeted therapy (Lu-PSMA) has been mainly investigated in the castration-resistant setting, but might have a role in earlier settings such as neoadjuvant treatment. SUMMARY: Novel molecular imaging using PSMA-based tracers could significantly improve PCa management in the diagnosis, staging, and intraoperative guidance settings, potentially leading to personalized and effective treatment decisions.

Active surveillance should not be routinely considered in ISUP grade group 2 prostate cancer.

Active surveillance has been proposed as a therapeutic option in selected intermediate risk patients with biopsy grade group 2 prostate cancer. However, its oncologic safety in this setting is debated. Therefore, we conducted a non-systematic literature research of contemporary surveillance protocols including patients with grade group 2 disease to collect the most recent evidence in this setting. Although no randomized controlled trial compared curative-intent treatments, namely radical prostatectomy and radiotherapy vs. active surveillance in patients with grade group 2 disease, surgery is associated with a benefit in terms of disease control and survival when compared to expectant management in the intermediate risk setting. Patients with grade group 2 on active surveillance were at higher risk of disease progression and treatment compared to their grade group 1 counterparts. Up to 50% of those patients were eventually treated at 5 years, and the metastases-free survival rate was as low as 85% at 15-years. When considering low- and intermediate risk patients treated with radical prostatectomy, grade group 2 was one of the strongest predictors of grade upgrading and adverse features. Available data is insufficient to support the oncologic safety of active surveillance in all men with grade group 2 prostate cancer. Therefore, those patients should be counselled regarding the oncologic efficacy of upfront active treatment modalities and the lack of robust long-term data supporting the safety of active surveillance in this setting.