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

Follow-up in Active Surveillance for Prostate Cancer: Strict Protocol Adherence Remains Important for PRIAS-ineligible Patients

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Multiparametric Magnetic Resonance Imaging Should Be Preferred Over Digital Rectal Examination for Prostate Cancer Local Staging and Disease Risk Classification

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External validation of the Martini nomogram for prediction of side-specific extraprostatic extension of prostate cancer in patients undergoing robot-assisted radical prostatectomy

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Improved depth perception with three-dimensional auxiliary display and computer generated three-dimensional panoramic overviews in robot-assisted laparoscopy

In comparison to open surgery, endoscopic surgery offers impaired depth perception and narrower field-of-view. To improve depth perception, the Da Vinci robot offers three-dimensional (3-D) video on the console for the surgeon but not for assistants, although both must collaborate. We improved the shared perception of the whole surgical team by connecting live 3-D monitors to all three available Da Vinci generations, probed user experience after two years by questionnaire, and compared time measurements of a predefined complex interaction task performed with a 3-D monitor versus two-dimensional. Additionally, we investigated whether the complex mental task of reconstructing a 3-D overview from an endoscopic video can be performed by a computer and shared among users. During the study, 925 robot-assisted laparoscopic procedures were performed in three hospitals, including prostatectomies, cystectomies, and nephrectomies. Thirty-one users participated in our questionnaire. Eighty-four percent preferred 3-D monitors and 100% reported spatial-perception improvement. All participating urologists indicated quicker performance of tasks requiring delicate collaboration (e.g., clip placement) when assistants used 3-D monitors. Eighteen users participated in a timing experiment during a delicate cooperation task in vitro. Teamwork was significantly (40%) faster with the 3-D monitor. Computer-generated 3-D reconstructions from recordings offered very wide interactive panoramas with educational value, although the present embodiment is vulnerable to movement artifacts

External Validation of Models Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients

Background: Multiple statistical models predicting lymph node involvement (LNI) in prostate cancer (PCa) exist to support clinical decision-making regarding extended pelvic lymph node dissection (ePLND). Objective: To validate models predicting LNI in Dutch PCa patients. Design, setting, and participants: Sixteen prediction models were validated using a patient cohort of 1001 men who underwent ePLND. Patient characteristics included serum prostate specific antigen (PSA), cT stage, primary and secondary Gleason scores, number of biopsy cores taken, and number of positive biopsy cores. Outcome measurements and statistical analysis: Model performance was assessed using the area under the receiver operating characteristic curve (AUC). Calibration plots were used to visualize over- or underestimation by the models. Results and limitations: LNI was identified in 276 patients (28%). Patients with LNI had higher PSA, higher primary Gleason pattern, higher Gleason score, higher number of nodes harvested, higher number of positive biopsy cores, and higher cT stage compared to patients without LNI. Predictions generated by the 2012 Briganti nomogram (AUC 0.76) and the Memorial Sloan Kettering Cancer Center (MSKCC) web calculator (AUC 0.75) were the most accurate. Calibration had a decisive role in selecting the most accurate models because of overlapping confidence intervals for the AUCs. Underestimation of LNI probability in patients had a predicted probability of <20%. The omission of model updating was a limitation of the study. Conclusions: Models predicting LNI in PCa patients were externally validated in a Dutch patient cohort. The 2012 Briganti and MSKCC nomograms were identified as the most accurate prediction models available. Patient summary: In this report we looked at how well models were able to predict the risk of prostate cancer spreading to the pelvic lymph nodes. We found that two models performed similarly in predicting the most accurate probabilities. Nomograms developed by Briganti et al and the Memorial Sloan Kettering Cancer Center were best at predicting lymph node involvement in prostate cancer patients. These models support clinical decision-making on whether to perform pelvic lymph node dissection

Development and External Validation of a Novel Nomogram to Predict Side-specific Extraprostatic Extension in Patients with Prostate Cancer Undergoing Radical Prostatectomy

BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). OBJECTIVE: To develop and externally validate nomograms including multiparametric magnetic resonance imaging (mpMRI) information to predict side-specific EPE. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1870 consecutive prostate cancer patients who underwent robot-assisted RP from 2014 to 2018 at three institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four multivariable logistic regression models were established, including combinations of patient-based and side-specific variables: prostate-specific antigen (PSA) density, highest ipsilateral International Society of Urological Pathology (ISUP) biopsy grade, ipsilateral percentage of positive cores on systematic biopsy, and side-specific clinical stage assessed by both digital rectal examination and mpMRI. Discrimination (area under the curve [AUC]), calibration, and net benefit of these models were assessed in the development cohort and two external validation cohorts. RESULTS AND LIMITATIONS: On external validation, AUCs of the four models ranged from 0.80 (95% confidence interval [CI] 0.68-0.88) to 0.83 (95% CI 0.72-0.90) in cohort 1 and from 0.77 (95% CI 0.62-0.87) to 0.78 (95% CI 0.64-0.88) in cohort 2. The three models including mpMRI staging information resulted in relatively higher AUCs compared with the model without mpMRI information. No major differences between the four models regarding net benefit were established. The model based on PSA density, ISUP grade, and mpMRI T stage was superior in terms of calibration. Using this model with a cut-off of 20%, 1980/2908 (68%) prostatic lobes without EPE would be found eligible for nerve sparing, whereas non-nerve sparing would be advised in 642/832 (77%) lobes with EPE. CONCLUSIONS: Our analysis resulted in a simple and robust nomogram for the prediction of side-specific EPE, which should be used to select patients for nerve-sparing RP. PATIENT SUMMARY: We developed a prediction model that can be used to assess accurately the likelihood of tumour extension outside the prostate. This tool can guide patient selection for safe nerve-sparing surgery

Confocal laser microscopy for assessment of surgical margins during radical prostatectomy

Objective: To evaluate the feasibility of confocal laser microscopy (CLM) for intraoperative margin assessment as faster alternative to neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during robot-assisted radical prostatectomy (RARP).  Patients and Methods: Surgical margins were assessed during 50 RARP procedures in patients scheduled for NeuroSAFE. Posterolateral sections were cut and imaged with CLM and further processed to conform with the NeuroSAFE protocol. Secondary resection (SR) was performed in case a positive surgical margin (PSM) was observed with NeuroSAFE. Afterwards, the CLM images were non-blinded assessed for the presence of PSMs. The accuracy of both NeuroSAFE and CLM was compared with conventional histopathology. Agreement for detection of PSMs between NeuroSAFE and CLM was evaluated with Cohen's kappa coefficient. Procedure times were compared with a Wilcoxon signed-ranks test.  Results: In total, 96 posterolateral sections of RP specimens were evaluated for the presence of PSMs. CLM identified 15 (16%) PSMs and NeuroSAFE identified 14 (15%) PSMs. CLM had a calculated sensitivity, specificity, positive predictive value and negative predictive value of 86%, 96%, 80% and 98% respectively for the detection of PSMs compared to definite pathology. After SR, residual tumour was found in six of 13 cases (46%), which were all identified by both techniques. There was a substantial level of agreement between CLM and NeuroSAFE (κ = 0.80). The median procedure time for CLM was significantly shorter compared to NeuroSAFE (8 vs 50 min, P < 0.001). The main limitation of this study was the non-blinded assessment of the CLM images.  Conclusions: Compared to NeuroSAFE, CLM is a promising technique for intraoperative margin assessment and is able to reduce the time of intraoperative margin assessment

Optimizing the risk threshold of lymph node involvement for performing extended pelvic lymph node dissection in prostate cancer patients: a cost-effectiveness analysis

Background: Extended pelvic lymph node dissection (ePLND) may be omitted in prostate cancer (CaP) patients with a low predicted risk of lymph node involvement (LNI). The aim of the current study was to quantify the cost-effectiveness of using different risk thresholds for predicted LNI in CaP patients to inform decision making on omitting ePLND. Methods: Five different thresholds (2%, 5%, 10%, 20%, and 100%) used in practice for performing ePLND were compared using a decision analytic cohort model with the 100% threshold (i.e., no ePLND) as reference. Compared outcomes consisted of quality-adjusted life years (QALYs) and costs. Baseline characteristics for the hypothetical cohort were based on an actual Dutch patient cohort containing 925 patients who underwent ePLND with risks of LNI predicted by the Memorial Sloan Kettering Cancer Center web-calculator. The best strategy was selected based on the incremental cost effectiveness ratio when applying a willingness to pay (WTP) threshold of €20,000 per QALY gained. Probabilistic sensitivity analysis was performed with Monte Carlo simulation to assess the robustness of the results. Results: Costs and health outcomes were lowest (€4,858 and 6.04 QALYs) for the 100% threshold, and highest (€10,939 and 6.21 QALYs) for the 2% threshold, respectively. The incremental cost effectiveness ratio for the 2%, 5%, 10%, and 20% threshold compared with the first threshold above (i.e., 5%, 10%, 20%, and 100%) were €189,222/QALY, €130,689/QALY, €51,920/QALY, and €23,187/QALY respectively. Applying a WTP threshold of €20.000 the probabilities for the 2%, 5%, 10%, 20%, and 100% threshold strategies being cost-effective were 0.0%, 0.3%, 4.9%, 30.3%, and 64.5% respectively. Conclusion: Applying a WTP threshold of €20.000, completely omitting ePLND in CaP patients is cost-effective compared to other risk-based strategies. However, applying a 20% threshold for probable LNI to the Briganti 2012 nomogram or the Memorial Sloan Kettering Cancer Center web-calculator, may be a feasible alternative, in particular when higher WTP values are considered

External validation of the Memorial Sloan Kettering Cancer Centre and Briganti nomograms for the prediction of lymph node involvement of prostate cancer using clinical stage assessed by magnetic resonance imaging

Objectives: To evaluate the impact of using clinical stage assessed by multiparametric magnetic resonance imaging (mpMRI) on the performance of two established nomograms for the prediction of pelvic lymph node involvement (LNI) in patients with prostate cancer. Patients and Methods: Patients undergoing robot-assisted extended pelvic lymph node dissection (ePLND) from 2015 to 2019 at three teaching hospitals were retrospectively evaluated. Risk of LNI was calculated four times for each patient, using clinical tumour stage (T-stage) assessed by digital rectal examination (DRE) and by mpMRI, in the Memorial Sloan Kettering Cancer Centre (MSKCC; 2018) and Briganti (2012) nomograms. Discrimination (area under the curve [AUC]), calibration, and the net benefit of these four strategies were assessed and compared. Results: A total of 1062 patients were included, of whom 301 (28%) had histologically proven LNI. Using DRE T-stage resulted in AUCs of 0.71 (95% confidence interval [CI] 0.70–0.72) for the MSKCC and 0.73 (95% CI 0.72–0.74) for the Briganti nomogram. Using mpMRI T-stage, the AUCs were 0.72 (95% CI 0.71–0.73) for the MSKCC and 0.75 (95% CI 0.74–0.76) for the Briganti nomogram. mpMRI T-stage resulted in equivalent calibration compared with DRE T-stage. Combined use of mpMRI T-stage and the Briganti 2012 nomogram was shown to be superior in terms of AUC, calibration, and net benefit. Use of mpMRI T-stage led to increased sensitivity for the detection of LNI for all risk thresholds in both models, countered by a decreased specificity, compared with DRE T-stage. Conclusion: T-stage as assessed by mpMRI is an appropriate alternative for T-stage assessed by DRE to determine nomogram-based risk of LNI in patients with prostate cancer, and was associated with improved model performance of both the MSKCC 2018 and Briganti 2012 nomograms