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.

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.

Added Value of Prostate-specific Antigen Density in Selecting Prostate Biopsy Candidates Among Men with Elevated Prostate-specific Antigen and PI-RADS ≥3 Lesions on Multiparametric Magnetic Resonance Imaging of the Prostate: A Systematic Assessment by PI-RADS Score.

BACKGROUND: A significant proportion of patients with positive multiparametric magnetic resonance imaging (mpMRI; Prostate Imaging-Reporting and Data System [PI-RADS] scores of 3-5) have negative biopsy results. OBJECTIVE: To systematically assess all prostate-specific antigen density (PSAD) values and identify an appropriate cutoff for identification of patients with positive mpMRI who could potentially avoid biopsy on the basis of their PI-RADS score. DESIGN, SETTING, AND PARTICIPANTS: The study included a cohort of 1341 patients with positive mpMRI who underwent combined targeted and systematic biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Multivariable logistic regression analysis (MVA) was used to assess the association between PSAD and the risk of clinically significant prostate cancer (csPCa, grade group ≥2) after adjusting for confounders. We used locally weighted scatterplot smoothing to explore csPCa risk according to PSAD and PI-RADS scores. PSAD utility was observed only for patients with PI-RADS 3 lesions, so we plotted the effect of each PSAD value as a cutoff for this subgroup in terms of biopsies saved, csPCa cases missed, and clinically insignificant PCa (ciPCa, grade group 1) cases not detected. RESULTS AND LIMITATIONS: Overall, 667 (50%) csPCa cases were identified. On MVA, PSAD independently predicted csPCa (odds ratio 1.57; p < 0.001). For PI-RADS ≥4 lesions, the csPCa risk was ≥40% regardless of PSAD. Conversely, among patients with PI-RADS 3 lesions, csPCa risk ranged from 0% to 60% according to PSAD values, and a PSAD cutoff of 0.10 ng/ml/cm3 corresponded to a threshold probability of 10% for csPCa. Using this PSAD cutoff for patients with PI-RADS 3 lesions would have saved 32% of biopsies, missed 7% of csPCa cases, and avoided detection of 34% of ciPCa cases. Limitations include selection bias and the high experience of the radiologists and urologists involved. CONCLUSIONS: Patients with PI-RADS ≥4 lesions should undergo prostate biopsy regardless of their PSAD, while PSAD should be used to stratify patients with PI-RADS 3 lesions. Using a threshold probability of 10% for csPCa, our data suggest that the appropriate strategy is to avoid biopsy in patients with PI-RADS 3 lesions and PSAD <0.10 ng/ml/cm3. Our results also provide information to help in tailoring an appropriate strategy for every patient with positive mpMRI findings. PATIENT SUMMARY: We investigated whether a cutoff value for PSAD (prostate-specific antigen density) could identify patients with suspicious prostate lesions on MRI (magnetic resonance imaging) who could avoid biopsy according to the PI-RADS score for their scan. We found that patients with PI-RADS ≥4 should undergo prostate biopsy regardless of their PSAD. A PSAD cutoff of 0.10 should be used to stratify patients with PI-RADS 3.

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.

The Highest Grade Group Does Not Drive the Risk of Recurrence when Systematic and Multiparametric Magnetic Resonance Imaging (MRI)-targeted Biopsies are Discordant: Preliminary Findings Using Radical Prostatectomy Pathology as a Surrogate for MRI-targeted Biopsy Grade.

Pathology grading of prostate biopsy follows the rule that the highest International Society of Urological Pathology grade group (GG) is the GG assigned. This rule was developed in the systematic biopsy (SBx) era and makes sense when samples are from very different areas of the prostate. This rule has been kept for multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (MRI-TBx), for which multiple samples-targeted and systematic-are taken from small areas. In particular, if the results for SBx and MRI-TBx are discordant, the patient is assigned the higher GG. However, the most appropriate grading when MRI-TBx and SBx grades are discordant has never been investigated empirically. A cohort of patients who have undergone SBx and MRI-TBx with long oncological follow-up does not yet exist. To estimate the risk of recurrence for every combination of biopsy and pathological grades, we used the GG on radical prostatectomy (RP) as a surrogate for GG on MRI-TBx GG surrogate. We analyzed data for 12 468 men who underwent SBx and RP at a tertiary referral center and assessed 5-yr biochemical recurrence-free survival (bRFS) for each pairwise combination of biopsy and surgical GG results. We found that for cases with discordant SBx and RP grades, the risk of recurrence was intermediate, irrespective of whether the highest grade was at RP or SBx. For instance, the 5-yr bRFS rate was 57% for men with GG 3 on RP and 60% for men with GG 3 on SBx, but 63% for men with RP GG 3 and SBx GG 2, and 79% for men with RP GG 2 and SBx GG 3. Translating these findings to MRI-TBx casts doubt on current grading practice: when GGs are discordant between SBx and MRI-TBx, the risk of biochemical recurrence risk is not driven by the highest grade but by an intermediate between the two grades. Our findings should motivate studies assessing long-term outcomes for patients undergoing both MRI-TBx and SBx with a view to empirically evaluating current grading practices. PATIENT SUMMARY: Patients with prostate cancer may undergo two biopsy types: (1) systematic biopsy, for which sampling follows a systematic template; and (2) targeted biopsy, for which samples are taken from lesions detected on scans. There may be a difference in prostate cancer grade identified by the two approaches. In such cases, the risk of cancer recurrence seems to be predicted by an intermediate grade between the lower and higher grades.

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.

Cancer-Specific Mortality Differences in Specimen-Confined Radical Prostatectomy Patients According to Lymph Node Invasion.

PURPOSE: To test cancer-specific mortality (CSM) differences in specimen-confined (pT2) prostate cancer (PCa) at radical prostatectomy (RP) with lymph node dissection (LND) according to lymph node invasion (LNI). METHODS: RP + LND pT2 PCa patients were identified (surveillance, epidemiology, and end results 2010-2015). CSM-FS rates were tested in Kaplan-Meier plots and multivariable Cox-regression (MCR) models. Sensitivity analyses respectively addressing patients with 6 or more lymph nodes analyzed and pT2 pN1 patients were performed. RESULTS: Overall, 32,258 patients with pT2 PCa at RP + LND were identified. Of these, 448 (1.4%) patients harbored LNI. Five-year CSM-free estimates were 99.6% for pN0 vs. 96.4% for pN1 (P < .001). In MCR models, pN1 (HR: 3.4, P < .001) independently predicted higher CSM. In sensitivity analyses addressing patients with 6 or more lymph nodes analyzed (n = 15,437), 328 (2.1%) pN1 patients were identified. In this subgroup, 5-year CSM-free estimates were 99.6% for pN0 vs. 96.3% for pN1 (P < .001) and, in MCR models, pN1 independently predicted higher CSM (HR: 4.4, P < .001). In sensitivity analyses addressing pT2 pN1 patients, 5-year CSM-free estimates were 99.3, 100 and 84.8% for ISUP GG 1-3 vs. 4 vs. 5, respectively (P < .001). CONCLUSIONS: In patients with pT2 PCa a small proportion harbor LNI (1.4%-2.1%). In such patients, CSM rate is higher (HR 3.4-4.4, P < .001). This higher CSM risk seems to virtually exclusively apply to ISUP GG5 patients (84.8% 5-year CSM-free rate).

Identification of the Optimal Candidates for Nodal Staging with Extended Pelvic Lymph Node Dissection Among Prostate Cancer Patients Who Underwent Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography. External Validation of the Memorial Sloan Kettering Cancer Center and Briganti Nomograms and Development of a Novel Tool.

BACKGROUND: Although the therapeutic role of extended pelvic lymph node dissection (ePLND) in patients with prostate cancer (PCa) is still under debate, this procedure is recommended for staging purposes in selected cases. Nomograms for predicting lymph node invasion (LNI) do not account for prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, which is characterized by a high negative predictive value for nodal metastases. OBJECTIVE: To externally validate models predicting LNI in patients with miN0M0 PCa at PSMA PET and to develop a novel tool in this setting. DESIGN, SETTING, AND PARTICIPANTS: Overall, 458 patients with miN0M0 disease undergoing radical prostatectomy (RP) and ePLND at 12 centers between 2017 and 2022 were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSES: Available tools were externally validated using calibration plots, the area under the receiver operating characteristic curve (AUC), and decision curve analyses to assess calibration, discrimination, and the net benefit. A novel coefficient-based model was developed, internally validated, and compared with available tools. RESULTS AND LIMITATIONS: Overall, 53 patients (12%) had LNI. The AUC was 69% for the Briganti 2012, 64% for the Briganti 2017, 73% for the Briganti 2019, and 66% for the Memorial Sloan Kettering Cancer Center nomogram. Multiparametric magnetic resonance imaging stage, biopsy grade group 5, the diameter of the index lesion, and the percentage of positive cores at systematic biopsy were independent predictors of LNI (all p ≤ 0.04). Internal cross-validation confirmed a coefficient-based model with AUC of 78%, better calibration, and a higher net benefit in comparison to the other nomograms assessed. Use of a 5% cutoff would have spared 47% ePLND procedures (vs 13% for the Briganti 2019 nomogram) at the cost of missing only 2.1% LNI cases . The lack of central review of imaging and pathology represents the main limitation. CONCLUSIONS: Tools for predicting LNI are associated with suboptimal performance for men with miN0M0 PCa. We propose a novel model for predicting LNI that outperforms available tools in this population. PATIENT SUMMARY: Tools currently used to predict lymph node invasion (LNI) in prostate cancer are not optimal for men with negative node findings on PET (positron emission tomography) scans, leading to a high number of unnecessary extended pelvic lymph node dissection (ePLND) procedures. A novel tool should be used in clinical practice to identify candidates for ePLND to reduce the risk of unnecessary procedures without missing LNI cases.

Impact of prostate imaging quality (PI-QUAL) score on the detection of clinically significant prostate cancer at biopsy.

PURPOSE: To investigate the impact of Prostate Imaging Quality (PI-QUAL) scores on the diagnostic performance of multiparametric MRI (mpMRI) in a targeted biopsy cohort. PATIENTS AND METHODS: 300 patients who underwent both mpMRI and biopsy were included. PI-QUAL scores were retrospectively assigned by two radiologists in consensus and were correlated to pre-biopsy PI-RADS scores and biopsy outcomes. Clinically significant prostate cancer (csPCa) was defined as ISUP grade ≥ 2. RESULTS: Image quality was optimal (PI-QUAL ≥ 4) in 249/300 (83%) and suboptimal (PI-QUAL < 4) in 51/300 (17%). The proportion of PI-RADS 3 scores referred for biopsy was higher in scans of suboptimal vs optimal quality (51% vs 33%). For PI-QUAL < 4 scans, the positive predictive value (PPV) was lower compared to PI-QUAL ≥ 4 (35% [95%CI: 22, 48] vs 48% [95%CI: 41, 55]; difference -13% [95%CI: -27, 2]; p 0.090), as was the detection rate of csPCa in both PI-RADS 3 and PI-RADS 4-5 (15% vs 23% and 56 vs 63%, respectively). The overall MRI quality increased over time. CONCLUSIONS: Scan quality may affect the diagnostic performance of prostate mpMRI in patients undergoing MRI-guided biopsy. Scans of suboptimal quality (PI-QUAL < 4) were associated with lower PPV for csPCa.

Impact of the time elapsed between prostate biopsy and surgery on the accuracy of nomograms predicting lymph node invasion in patients with clinically localized prostate cancer.

We aimed to investigate whether the performance characteristics of available nomograms predicting lymph node invasion (LNI) in prostate cancer patients undergoing radical prostatectomy (RP) change according to the time elapsed between diagnosis and surgery. We identified 816 patients who underwent RP with extended pelvic lymph node dissection (ePLND) after combined prostate biopsy at 6 referral centers. We plotted the accuracy (ROC-derived area under the curve [AUC]) of each Briganti nomogram according to the time elapsed between biopsy ad RP. We then tested whether discrimination of the nomograms improved after accounting for the time elapsed between biopsy ad RP. The median time between biopsy and RP was 3 months. The LNI rate was 13%. The discrimination of each nomogram decreased with increasing time elapsed between biopsy and surgery, where the AUC of the 2019 Briganti nomogram was 88% vs. 70% for men undergoing surgery <2 vs. >6 months from the biopsy. The addition of the time elapsed between biopsy ad RP improved the accuracy of all available nomograms (P < 0.003), with the Briganti 2019 nomogram showing the highest discrimination. Clinicians should be aware that the discrimination of available nomograms decreases according to the time elapsed between diagnosis and surgery. The indication of ePLND should be carefully evaluated in men below the LNI cut-off who had a diagnosis more than 6 months before RP. This has important implications when considering the longer waiting lists related to the impact of COVID-19 on healthcare systems.

Implementation of 4Kscore as a Secondary Test Before Prostate Biopsy: Impact on US Population Trends for Prostate Cancer.

Prostate cancer screening using prostate-specific antigen (PSA) reduces prostate cancer mortality at the cost of unnecessary prostate biopsy, overdiagnosis, and overtreatment. Several secondary tests have been developed to restrict biopsy to men at the greatest risk of high-grade disease. 4Kscore is a widely used secondary test that has been shown to reduce biopsy rates by approximately two-thirds in routine clinical practice. We estimated how 4Kscore implementation has affected cancer trends in the US population. We combined data from the US validation study of 4Kscore with data from the diagnostic test impact study, using a basis of 70 000 on-label 4Kscore tests performed annually. We estimate that each year, 4Kscore leads to 45 200 fewer biopsies and 9400 fewer overdiagnoses of low-grade cancer, at the cost of delayed diagnosis of high-grade prostate cancer for 3450 patients, of whom two-thirds have International Society of Urological Pathology grade group 2 disease. These findings need to be taken into consideration when studying epidemiologic trends in prostate cancer. They also suggest that high levels of overdiagnosis and overtreatment are not inevitable characteristics of PSA screening, but can be mitigated by additional tests. Patient summary: We estimate that use of a test called 4Kscore to predict the probability that a patient has high-grade prostate cancer has significantly reduced the number of unnecessary biopsies and overdiagnosis of low-grade cancer in the USA. These decisions may result in delayed diagnosis of high-grade cancer in some patients. 4Kscore is a useful additional test in the management of prostate cancer.

Is Active Surveillance an Option for the Management of Men with Low-grade Prostate Cancer and a Positive Family History? Results from a Large, Single-institution Series.

BACKGROUND: Family history (FH) of prostate cancer (PCa) is associated with an increased risk of PCa and adverse disease features. However, whether patients with localized PCa and FH could be considered for active surveillance (AS) remains controversial. OBJECTIVE: To assess the association between FH and reclassification of AS candidates, and to define predictors of adverse outcomes in men with positive FH. DESIGN, SETTING, AND PARTICIPANTS: Overall, 656 patients with grade group (GG) 1 PCa included in an AS protocol at a single institution were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Kaplan-Meier analyses assessed the time to reclassification (GG ≥2 and GG ≥3 at follow-up biopsies) overall and according to FH status. Multivariable Cox regression tested the impact of FH on reclassification and identified the predictors among men with FH. Men treated with delayed radical prostatectomy (n = 197) or external-beam radiation therapy (n = 64) were identified, and the impact of FH on oncologic outcomes was assessed. RESULTS AND LIMITATIONS: Overall, 119 men (18%) had FH. The median follow-up was 54 mo (interquartile range 29-84 mo), and 264 patients experienced reclassification. The 5-yr reclassification-free survival rate was 39% versus 57% for FH versus no FH (p = 0.006), and FH was associated with reclassification to GG ≥2 (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.19-2.15, p = 0.002). In men with FH, the strongest predictors of reclassification were prostate-specific antigen (PSA) density (PSAD), high-volume GG 1 (≥33% of cores involved or ≥50% of any core involved), and suspicious magnetic resonance imaging (MRI) of the prostate (HRs 2.87, 3.04, and 3.87, respectively; all p < 0.05). No association between FH, adverse pathologic features, and biochemical recurrence was observed (all p > 0.05). CONCLUSIONS: Patients with FH on AS are at an increased risk of reclassification. Negative MRI, low disease volume, and low PSAD identify men with FH and a low risk of reclassification. Nonetheless, sample size and wide CIs entail caution in drawing conclusions based on these results. PATIENT SUMMARY: We tested the impact of family history in men on active surveillance for localized prostate cancer. A significant risk of reclassification, but not adverse oncologic outcomes after deferred treatment, prompts the need for cautious discussion with these patients, without precluding initial expectant management.

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.

Prostate-specific Antigen Density Cutoff of 0.15 ng/ml/cc to Propose Prostate Biopsies to Patients with Negative Magnetic Resonance Imaging: Efficient Threshold or Legacy of the Past?

BACKGROUND: A prostate-specific antigen density (PSAd) cutoff of 0.15 ng/ml/cc is a commonly recommended threshold to identify patients with negative prostate magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We were unable to find any study that explicitly examined the properties of this threshold compared with others. OBJECTIVE: To investigate whether the 0.15 cutoff is justified for selecting patients at risk of harboring high-grade cancer (Gleason score ≥3 + 4) despite negative MRI. DESIGN, SETTING, AND PARTICIPANTS: A cohort of 8974 prostate biopsies provided by the Prostate Biopsy Collaborative Group (PBCG) was included in the study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Locally weighted scatterplot smoothing was used to investigate whether there was a change in the risk of high-grade cancer around this value. We examined whether the use of this cutoff in patients with negative MRI corresponds to a reasonable threshold probability for a biopsy (defined as a 10% risk of high-grade disease). To do so, we applied the negative likelihood ratio of MRI, calculated from eight studies on prostate MRI, to the risk curve derived from the PBCG. RESULTS AND LIMITATIONS: There was no discontinuity in the risk of high-grade prostate cancer at a PSAd cutoff of 0.15. This cutoff corresponded to a probability of high-grade disease ranging from 2.6% to 10%, depending on MRI accuracy. Using 10% as threshold probability, the corresponding PSAd cutoff varied between 0.15 and 0.38, with the threshold increasing for greater MRI accuracy. Possible limitations include difference between studies on MRI and the use of ultrasound to measure prostate volume. CONCLUSIONS: The 0.15 cutoff to recommend prostate biopsies in patients with negative MRI is justified only under an extreme scenario of poor MRI properties. We recommend a value of at least ≥0.20. Our results suggest the need for future studies to look at how to best identify patients who need prostate biopsies despite negative MRI, likely by using individualized risk prediction. PATIENT SUMMARY: In this study, we investigated whether the commonly used prostate-specific antigen density cutoff of 0.15 is justified to identify patients with negative magnetic resonance imaging (MRI) who should proceed to a prostate biopsy. We found that this cutoff is appropriate only in case of very poor MRI quality, and a higher cutoff (≥0.20) should be used for the average MRI.

Impact of Early Dorsal Venous Complex Ligation on Urinary Continence Recovery after Robot-assisted Radical Prostatectomy: Results from a Phase 3 Randomized Controlled Trial.

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

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer.

Objective: To evaluate the relationship between pre-operative PSA value, 68Ga-prostate-specific-membrane-antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods: The study included 164 patients diagnosed with ≤2 pelvic lymph-node recurrence(s) of PCa documented on 68Ga-PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high-volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)-free survival after sLND was calculated using multivariable analyses and plotted over pre-operative PSA value. Results: Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre-operative PSA value, with highest rates for patients with pre-operative PSA > 1.5 ng/ml (pelvic-only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre-operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa.

Long-term oncologic outcomes of robot-assisted radical cystectomy: update series from a high-volume robotic center beyond 10 years of follow-up.

Long-term oncologic data on patients undergoing robot-assisted radical cystectomy (RARC) for non-metastatic bladder cancer (BCa) are limited. The purpose of this study is to describe long-term oncologic outcomes of patients receiving robotic radical cystectomy at a high-volume European Institution. We analyzed data of 107 patients treated with RARC between 2003 and 2012 at a high-volume robotic center. Clinical, pathologic, and survival data at the latest follow-up were collected. Clinical recurrence (CR)-free survival, cancer-specific mortality (CSM)-free survival, and overall survival (OS) were plotted using Kaplan-Meier survival curves. Cox proportional hazard models investigated predictors of CR and CSM. Competing-risk regressions were utilized to depict cumulative incidences of death from BCa and death from other causes after RARC at long term. Pathologic nonorgan-confined BCa was found in 40% of patients, and 7 (7%) patients had positive soft tissue surgical margins. Median (interquartile range [IQR]) number of nodes removed was 11 (6, 14), and 26% of patients had pN + disease. Median (IQR) follow-up for survivors was 123 (117, 149) months. The 12-year CR-free, CSM-free and overall survival were 55% (95% confidence interval [CI] 44%, 65%), 62% (95% CI 50%, 72%), and 34% (95% CI 24%, 44%), respectively. Nodal involvement on final pathology was associated with poor prognosis on multivariable competing risk analysis. The cumulative incidence of non-cancer death exceeded that of death from BCa after approximately ten years after RARC. We provided relevant data on oncologic outcomes of RARC at a high-volume robotic center, with acceptable rates of clinical recurrence and cancer-specific survival at long-term. In patients treated with RARC, the cumulative incidence of death from causes other than BCa is non-negligible, and should be taken into consideration for post-operative follow-up.

Are Urologists Ready for Interpretation of Multiparametric MRI Findings? A Prospective Multicentric Evaluation.

Aim: To assess urologists' proficiency in the interpretation of multiparametric magnetic resonance imaging (mpMRI). Materials and Methods: Twelve mpMRIs were shown to 73 urologists from seven Italian institutions. Responders were asked to identify the site of the suspicious nodule (SN) but not to assign a PIRADS score. We set an a priori cut-off of 75% correct identification of SN as a threshold for proficiency in mpMRI reading. Data were analyzed according to urologists' hierarchy (UH; resident vs. consultant) and previous experience in fusion prostate biopsies (E-fPB, defined as <125 vs. ≥125). Additionally, we tested for differences between non-proficient vs. proficient mpMRI readers. Multivariable logistic regression analyses (MVLRA) tested potential predictors of proficiency in mpMRI reading. Results: The median (IQR) number of correct identifications was 8 (6−8). Anterior nodules (number 3, 4 and 6) represented the most likely prone to misinterpretation. Overall, 34 (47%) participants achieved the 75% cut-off. When comparing consultants vs. residents, we found no differences in terms of E-fPB (p = 0.9) or in correct identification rates (p = 0.6). We recorded higher identification rates in urologists with E-fBP vs. their no E-fBP counterparts (75% vs. 67%, p = 0.004). At MVLRA, only E- fPB reached the status of independent predictor of proficiency in mpMRI reading (OR: 3.4, 95% CI 1.2−9.9, p = 0.02) after adjusting for UH and type of institution. Conclusions: Despite urologists becoming more familiar with interpretation of mpMRI, their results are still far from proficient. E-fPB enhances the proficiency in mpMRI interpretation.