Classification of subtask types and skill levels in robot-assisted surgery using EEG, eye-tracking, and machine learning.

BACKGROUND: Objective and standardized evaluation of surgical skills in robot-assisted surgery (RAS) holds critical importance for both surgical education and patient safety. This study introduces machine learning (ML) techniques using features derived from electroencephalogram (EEG) and eye-tracking data to identify surgical subtasks and classify skill levels. METHOD: The efficacy of this approach was assessed using a comprehensive dataset encompassing nine distinct classes, each representing a unique combination of three surgical subtasks executed by surgeons while performing operations on pigs. Four ML models, logistic regression, random forest, gradient boosting, and extreme gradient boosting (XGB) were used for multi-class classification. To develop the models, 20% of data samples were randomly allocated to a test set, with the remaining 80% used for training and validation. Hyperparameters were optimized through grid search, using fivefold stratified cross-validation repeated five times. Model reliability was ensured by performing train-test split over 30 iterations, with average measurements reported. RESULTS: The findings revealed that the proposed approach outperformed existing methods for classifying RAS subtasks and skills; the XGB and random forest models yielded high accuracy rates (88.49% and 88.56%, respectively) that were not significantly different (two-sample t-test; P-value = 0.9). CONCLUSION: These results underscore the potential of ML models to augment the objectivity and precision of RAS subtask and skill evaluation. Future research should consider exploring ways to optimize these models, particularly focusing on the classes identified as challenging in this study. Ultimately, this study marks a significant step towards a more refined, objective, and standardized approach to RAS training and competency assessment.

Impact of an NCCN-Compliant Multidisciplinary Conference on Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: We sought to investigate the impact of an NCCN-compliant multidisciplinary conference on treatment decisions of patients with localized prostate cancer. METHODS: A retrospective review of our quality assurance localized prostate cancer database was performed. All patients with localized prostate cancer who sought a second opinion at Roswell Park Comprehensive Cancer Center between 2009 and 2019 were presented to the multidisciplinary Localized Prostate Cancer Conference (LPCC) that includes urologists, radiation oncologists, pathologists, and patient advocates. Multivariable regression models were fit to evaluate variables associated with concordance between community recommendations, LPCC recommendations, and treatment received by patients. RESULTS: A total of 1,164 patients were identified, of whom 26% had NCCN very low-/low-risk, 27% had favorable intermediate-risk, 25% had unfavorable intermediate-risk, and 22% had high-/very high-risk prostate cancer. Pathology changed in 11% of patients after genitourinary pathologist review, which caused disease reclassification in 9%. Concordance between community and LPCC recommendations occurred in 78%, with lowest concordance for androgen deprivation therapy (21%) and radiotherapy (53%). Concordance between community recommendations and treatment received occurred in 65%, with lowest concordance for androgen deprivation therapy and radiotherapy; among those who were recommended radiotherapy as the only option by their community urologist, only 26% received it. Concordance between LPCC recommendations and treatment received occurred in 92%. CONCLUSIONS: Community recommendations differed from the multidisciplinary NCCN-compliant recommendations in 22% of patients, primarily for radiotherapy. Multidisciplinary recommendations matched the treatment received in 92% of patients compared with 65% for community recommendations.

NCCN Guidelines® Insights: Prostate Cancer Early Detection, Version 1.2023.

The NCCN Guidelines for Prostate Cancer Early Detection provide recommendations for individuals with a prostate who opt to participate in an early detection program after receiving the appropriate counseling on the pros and cons. These NCCN Guidelines Insights provide a summary of recent updates to the NCCN Guidelines with regard to the testing protocol, use of multiparametric MRI, and management of negative biopsy results to optimize the detection of clinically significant prostate cancer and minimize the detection of indolent disease.

Development and validation of nomogram to improve the specificity of multiparametric MRI for clinically significant prostate cancer.

OBJECTIVE: To develop and validate a nomogram to improve the specificity of prostate imaging reporting and data system (PI-RADS) on multiparametric magnetic resonance imaging (MRI) for clinically significant prostate cancer on targeted fusion biopsy. METHODS: A retrospective review of patients who underwent fusion biopsy for PI-RADS 3-5 lesions using UroNav and Artemis systems between 2016 and 2022 was performed. Patients were divided into those with CS disease on fusion biopsy (Gleason grade group ≥2) versus those without. Multivariable analysis was used to identify variables associated with CS disease. A 100-point nomogram was constructed, and ROC curve was generated. RESULTS: 1485 lesions (1032 patients) were identified, 510 (34%) were PI-RADS 3, 586 (40%) were PI-RADS 4, and 389 (26%) were PI-RADS 5. Of these, 11% of PI-RADS 3, 39% of PI-RADS 4, and 61% of PI-RADS 5 showed CS disease. CS disease was associated with older age (OR 1.04, 95% CI 1.02-1.06, p < 0.01), previous negative biopsy (OR 0.52, 95% CI 0.36-0.74, p < 0.01), presence of multiple PI-RADS 3-5 lesions (OR 0.61, 95% CI 0.45-0.83, p < 0.01), peripheral zone location (OR 1.88, 95% CI 1.30-2.70, p < 0.01), PSA density (OR 1.48 per 0.1 unit, 95% CI 1.33-1.64, p < 0.01), PI-RADS score 4 (OR 3.28, 95% CI 2.21-4.87, p < 0.01), and PI-RADS score 5 (OR 7.65, 95% CI 4.93-11.85, p < 0.01). Area under ROC curve was 82% for nomogram compared to 75% for PI-RADS score alone. CONCLUSION: We report a nomogram that combines PI-RADS score with other clinical parameters. The nomogram outperforms PI-RADS score for the detection of CS prostate cancer.

Excitation of a Single Compound by Light and Ultrasound Enhanced the Long-Term Cure of Mice Bearing Prostate Tumors.

Current treatment for prostate cancer is dependent on the stages of the cancer, recurrence, and genetic factors. Treatment varies from active surveillance or watchful waiting to prostatectomy, chemotherapy, and radiation therapy in combination or alone. Although radical prostate cancer therapy reduces the advancement of the disease and its mortality, the increased disease treatment associated morbidity, erectile dysfunction, and incontinence affect the quality of life of cancer survivors. To overcome these problems, photodynamic therapy (PDT) has previously been investigated using PhotofrinTM as a photosensitizer (PS). However, Photofrin-PDT has shown limitations in treating prostate cancer due to its limited tumor-specificity and the depth of light penetration at 630 nm (the longest wavelength absorption of PhotofrinTM). The results presented herein show that this limitation can be solved by using a near infrared (NIR) compound as a photosensitizer (PS) for PDT and the same agent also acts as a sonosensitizer for SDT (using ultrasound to activate the compound). Compared to light, ultrasound has a stronger penetration ability in biological tissues. Exposing the PS (or sonosensitizer) to ultrasound (US) initiates an electron-transfer process with a biological substrate to form radicals and radical ions (type I reaction). In contrast, exposure of the PS to light (PDT) generates singlet oxygen (type II reaction). Therefore, the reactive oxygen species (ROS) produced by SDT and PDT follow two distinct pathways, i.e., type I (oxygen independent) and type II (oxygen dependent), respectively, and results in significantly enhanced destruction of tumor cells. The preliminary in vitro and in vivo results in a PC3 cell line and tumor model indicate that the tumor specificality of the therapeutic agent(s) can be increased by targeting galectin-1 and galectin-3, known for their overexpression in prostate cancer.

Active Surveillance for Risk Stratification of All Small Renal Masses Lacking Predefined Clinical Criteria for Intervention.

PURPOSE: Despite general indolence of small renal masses and no known adversity from treatment delays, broad usage of active surveillance as a means to risk-stratify patients with small renal masses for more selective treatment has not been studied. We describe outcomes for a novel approach in which active surveillance was recommended to all patients with small renal masses lacking predefined progression criteria for intervention. MATERIALS AND METHODS: All nondialysis dependent patients with nonmetastatic small renal masses seen by 1 urologist at a comprehensive cancer center during January 2013-September 2017 were managed with active surveillance if standardized progression criteria for intervention were absent, with delayed intervention recommended only upon progression criteria for intervention development. Progression criteria for intervention were defined prospectively as small renal mass-related symptoms, unfavorable histology, cT3a stage or either of the following without benign neoplastic biopsy histology: longest tumor diameter >4 cm; growth rate >5 mm/year for longest tumor diameter ≤3 cm or >3 mm/year for longest tumor diameter >3 cm. RESULTS: In all, 96% (123/128) of patients with small renal masses lacked progression criteria for intervention at presentation and underwent active surveillance. With median/mean 31/34 months followup, none developed metastasis and 30% (37/123) developed progression criteria for intervention, 78% (29/37) of whom underwent delayed intervention. One (1%) patient crossed over to delayed intervention without progression criteria for intervention. Three-year progression criteria for intervention-free and delayed intervention-free rates were 72% and 75%, respectively. Delayed intervention resections were enriched (62%) for pT3 and/or nuclear grade 3-4 malignant pathology, with no benign resections. CONCLUSIONS: Active surveillance using predefined progression criteria for intervention in otherwise unselected patients with small renal masses allows intervention to be focused on at-risk small renal masses with common adverse pathology, avoiding treatment for most patients with small renal masses. Long-term delayed intervention and oncologic safety require study.

Automated differentiation of benign renal oncocytoma and chromophobe renal cell carcinoma on computed tomography using deep learning.

OBJECTIVES: To develop and evaluate the feasibility of an objective method using artificial intelligence (AI) and image processing in a semi-automated fashion for tumour-to-cortex peak early-phase enhancement ratio (PEER) in order to differentiate CD117(+) oncocytoma from the chromophobe subtype of renal cell carcinoma (ChRCC) using convolutional neural networks (CNNs) on computed tomography imaging. METHODS: The CNN was trained and validated to identify the kidney + tumour areas in images from 192 patients. The tumour type was differentiated through automated measurement of PEER after manual segmentation of tumours. The performance of this diagnostic model was compared with that of manual expert identification and tumour pathology with regard to accuracy, sensitivity and specificity, along with the root-mean-square error (RMSE), for the remaining 20 patients with CD117(+) oncocytoma or ChRCC. RESULTS: The mean ± sd Dice similarity score for segmentation was 0.66 ± 0.14 for the CNN model to identify the kidney + tumour areas. PEER evaluation achieved accuracy of 95% in tumour type classification (100% sensitivity and 89% specificity) compared with the final pathology results (RMSE of 0.15 for PEER ratio). CONCLUSIONS: We have shown that deep learning could help to produce reliable discrimination of CD117(+) benign oncocytoma and malignant ChRCC through PEER measurements obtained by computer vision.

Preclinical efficacy of dual mTORC1/2 inhibitor AZD8055 in renal cell carcinoma harboring a TFE3 gene fusion.

BACKGROUND: Renal cell carcinomas (RCC) harboring a TFE3 gene fusion (TfRCC) represent an aggressive subset of kidney tumors. Key signaling pathways of TfRCC are unknown and preclinical in vivo data are lacking. We investigated Akt/mTOR pathway activation and the preclinical efficacy of dual mTORC1/2 versus selective mTORC1 inhibition in TfRCC. METHODS: Levels of phosphorylated Akt/mTOR pathway proteins were compared by immunoblot in TfRCC and clear cell RCC (ccRCC) cell lines. Effects of the mTORC1 inhibitor, sirolimus, and the dual mTORC1/2 inhibitor, AZD8055, on Akt/mTOR activation, cell cycle progression, cell viability and cytotoxicity were compared in TfRCC cells. TfRCC xenograft tumor growth in mice was evaluated after 3-week treatment with oral AZD8055, intraperitoneal sirolimus and respective vehicle controls. RESULTS: The Akt/mTOR pathway was activated to a similar or greater degree in TfRCC than ccRCC cell lines and persisted partly during growth factor starvation, suggesting constitutive activation. Dual mTORC1/2 inhibition with AZD8055 potently inhibited TfRCC viability (IC50 = 20-50 nM) due at least in part to cell cycle arrest, while benign renal epithelial cells were relatively resistant (IC50 = 400 nM). Maximal viability reduction was greater with AZD8055 than sirolimus (80-90% versus 30-50%), as was the extent of Akt/mTOR pathway inhibition, based on significantly greater suppression of P-Akt (Ser473), P-4EBP1, P-mTOR and HIF1α. In mouse xenograft models, AZD8055 achieved significantly better tumor growth inhibition and prolonged mouse survival compared to sirolimus or vehicle controls. CONCLUSIONS: Akt/mTOR activation is common in TfRCC and a promising therapeutic target. Dual mTORC1/2 inhibition suppresses Akt/mTOR signaling more effectively than selective mTORC1 inhibition and demonstrates in vivo preclinical efficacy against TFE3-fusion renal cell carcinoma.

Blinded review of archival radical prostatectomy specimens supports that contemporary Gleason score 6 prostate cancer lacks metastatic potential.

BACKGROUND: Retrospective identification of Gleason pattern 4 in metastatic Gleason score 3 + 3 = 6 (GS6) radical prostatectomy (RP) specimens has suggested true GS6 prostate cancer (CaP) lacks metastatic potential. However, pathologist awareness of study design and metastasis outcomes at the time of RP review might have introduced upgrading bias. We used pathologist-blinded methodology for unbiased characterization of metastasis rates for contemporarily defined pathologic GS6 (pGS6) CaP. METHODS: An institutional RP database was queried to identify pGS6 patients with metastasis or concern for micrometastasis based on: 1) biochemical failure (BF) despite negative surgical margins or 2) incomplete biochemical response to salvage/adjuvant radiation. RP specimens were regraded independently by two genitourinary pathologists blinded to study aims or clinical outcomes. Additional blinding was performed by random inclusion of pGS6 control specimens from BF-free patients. Only upgrading identified independently by both pathologists was considered. RESULTS: Among 451 pGS6 patients identified, none had synchronous lymph node metastases and 43/451 (10%) suffered BF. Two patients (0.4%) developed metachronous metastasis during a 110-month median follow-up for BF patients. Both metastatic cases had Gleason pattern 4 on blinded RP review, as did 88% of cases with concern for micrometastasis versus 38% of control cases (P = 0.02). All BF patients (29/29) undergoing postoperative radiation had a complete biochemical response or Gleason pattern 4 on blinded RP review. CONCLUSIONS: Unbiased pathologist review of archival RP specimens supports absent metastatic potential for contemporarily defined GS6 CaP. Reduced postoperative monitoring is appropriate for pGS6, but may require pathology review to confirm absent Gleason pattern 4.

Implications of High Rates of Metastatic Prostate Cancer in BRCA2 Mutation Carriers.

BACKGROUND: Patients with germline BRCA2 gene mutations (BRCA2mut) have more aggressive prostate cancer. Analysis of all reported germline BRCA2mut prostate cancer cases allows better understanding of the clinicopathologic features and survival outcomes of these men. METHODS: A systematic review was performed with the MEDLINE database to capture articles evaluating clinicopathologic characteristics of men with BRCA2mut associated prostate cancer. Inclusion criteria were at least five subjects, confirmation of BRCA2mut status, and data for at least 2 clinical parameters of disease. Meta-analysis was performed on outcomes data. Chi-squared tests were used to compare disease features among men undergoing formal versus ad hoc screening, as well as an age of diagnosis less than versus greater than 65 years. Rates of metastatic disease among BRCA2mut cases were compared to rates among non-carrier control subjects and the general population using the SEER database. RESULTS: Twelve out of 289 studies met our inclusion criteria, representing 261 BRCA2mut men. Among carriers, the median age at diagnosis was 62 years and median PSA was 15 ng/dl with 95% of men having a PSA>3. Over 40% of BRCA2mut patients had T3/T4 disease and over 25% were metastatic at presentation. Survival was worse in BRCA2mut men with prostate cancer when compared to non-BRCA2mut subjects. BRCA2mut carriers had significantly higher rates of metastatic disease (18%) versus non-carrier controls (8%) and the SEER population (4%). CONCLUSIONS: BRCA2mut carriers are more likely to have poor risk of prostate cancer at presentation and exhibit worse oncologic outcomes relative to non-carriers, including a fourfold increase in metastatic disease. Younger men and those undergoing formal screening present with less advanced disease which supports a need for earlier identification and screening protocols. Additionally, this population may benefit from alternative therapeutic paradigms. Prostate 76:1135-1145, 2016. © 2016 Wiley Periodicals, Inc.

Clinical significance of prospectively assigned Gleason tertiary pattern 4 in contemporary Gleason score 3+3=6 prostate cancer.

OBJECTIVE: To determine the oncologic impact of prospectively assigned tertiary pattern 4 in contemporary Gleason score (GS) 3 + 3 = 6 radical prostatectomy (RP) specimens. PATIENTS AND METHODS: Oncologic outcomes were retrospectively reviewed for 720 consecutive patients from a single National Comprehensive Cancer Network (NCCN) center with at least 6 months follow-up after RP for GS3 + 3 = 6 (GS6, N = 222), GS6 with tertiary pattern 4 (GS6t4, N = 62), or GS3 + 4 = 7 (N = 436) prostate cancer, as prospectively graded since 2006 using the 2005 International Society of Urologic Pathologists criteria. Preoperative NCCN risk category, RP pathology, progression-free survival (PFS) and metastasis-free survival (MFS) were compared among the GS6, GS6t4, and GS3 + 4 = 7 groups using χ(2) , Kaplan-Meier, and log-rank analyses. RESULTS: The incidence of low NCCN preoperative risk classification for GS6t4 patients (63%) was less than that for GS6 patients (77%) while greater than that for GS3 + 4 = 7 patients (30%, P < 0.001). GS6t4 patients had RP pathologic features which were intermediate in risk between that of GS6 and GS3 + 4 = 7 based on extraprostatic extension (27% vs. 6% vs. 31%, respectively, P < 0.001) and mean percentage of prostate gland involvement (13% vs. 10% vs. 16%, respectively, P < 0.001). With a mean overall follow-up of 42 months, PFS for GS6t4 patients (5-year 85%) was intermediate between that of GS6 (5-year 93%) and GS3 + 4 = 7 (5-year 76%) patients (P < 0.001). The 5-year MFS rate was 100% for GS6 and GS6t4 patients compared to 97% for GS3 + 4 = 7 patients (P = 0.07). CONCLUSIONS: This study provides the longest follow-up to date for RP patients with prospectively assigned GS6t4 and supports a risk for adverse RP pathology and postoperative disease progression that is intermediate between GS6 and GS3 + 4 = 7. Whether a tertiary pattern 4 in GS6 disease increases the risk of metastasis is uncertain and requires longer term study. Given favorable oncologic outcomes, less stringent postoperative surveillance for both GS6 and GS6t4 patients may be warranted.

Lack of Impact of Robotic Assisted Laparoscopic Radical Prostatectomy on Intraoperative Levels of Prostate Cancer Circulating Tumor Cells.

PURPOSE: While the significance of circulating tumor cells in clinically localized cancer remains controversial, it has been reported that surgical tumor manipulation can increase circulating tumor cells, including during open prostatectomy. To our knowledge it is unknown whether this cell shedding also occurs during minimally invasive prostatectomy, which minimizes tumor palpation and uses earlier vascular control. We tested the impact of robotic assisted laparoscopic radical prostatectomy on intraoperative circulating tumor cell levels. MATERIALS AND METHODS: Circulating tumor cell counts were compared in peripheral blood specimens from 25 patients treated with robotic assisted laparoscopic radical prostatectomy preoperatively vs intraoperatively after prostate excision, in addition to 11 healthy blood donors. Circulating tumor cell detection was performed using EpCAM immunomagnetic enrichment and multiparametric flow cytometry quantification of viable EpCAM positive/prostate specific membrane antigen positive/CD45 negative cells. Intraoperative cell counts and increases were tested in univariable analyses for associations with perioperative variables, histopathology and postoperative progression. RESULTS: Circulating tumor cells were detected in 0% of healthy controls compared to 48% and 52% of prostatectomy cases preoperatively and intraoperatively, respectively (range 1 to 8 cells). There was no difference in the incidence or mean number of circulating tumor cells preoperatively vs intraoperatively. Of the patients 60% had no intraoperative change from preoperative levels. Intraoperative cell increases vs decreases were equally infrequent (each 20%) with no intraoperative increase greater than 1 circulating tumor cell. Intraoperative circulating tumor cell detection was not significantly associated with prostatectomy operative characteristics, histopathology or early postoperative progression at a median 21-month followup. CONCLUSIONS: Robotic assisted laparoscopic radical prostatectomy does not cause significant intraoperative increases in circulating tumor cells in contrast to historical reports of open prostatectomy. These findings may aid urologists in counseling candidates for robotic assisted laparoscopic radical prostatectomy regarding the possibility of intraoperative tumor cell shedding.

Outcomes of Scheduled vs For-Cause Biopsy Regimens for Prostate Cancer Active Surveillance.

PURPOSE: Active surveillance is a first line treatment option for patients with low risk prostate cancer but standardized regimens are lacking, including uniform protocols for surveillance prostate biopsy. We compared the outcomes of 2 active surveillance regimens that differ in whether a scheduled biopsy was performed in the absence of clinical progression. MATERIALS AND METHODS: We retrospectively reviewed the records of 313 consecutive patients with prostate cancer at a NCCN® (National Comprehensive Cancer Network®) institution who were assigned prospectively to 1 of 2 active surveillance biopsy regimens. A total of 149 patients underwent biopsy only for clinical concern (for-cause only) while 164 underwent for-cause biopsy plus scheduled annual or biannual biopsy. Times to biopsy, clinical progression, pathological reclassification and treatment were compared using Kaplan-Meier methodology. RESULTS: The for-cause only and scheduled plus for-cause biopsy groups were similar in NCCN risk category at active surveillance initiation. Median followup was 48 and 38 months, respectively. No significant difference was observed in prostate specific antigen dynamics or clinical progression rates. However, patients in the scheduled plus for-cause group underwent significantly more frequent biopsies (p <0.001) and experienced more biopsy related complications (p = 0.04), pathological reclassification (p = 0.02) and treatment conversion (p = 0.001). Adverse prostatectomy pathology (pT3 or greater and/or Gleason primary pattern 4) and early metastasis events were rare in both groups. CONCLUSIONS: Omitting a scheduled biopsy during active surveillance is associated with a decreased biopsy burden and treatment conversion. Although no increase in adverse pathology or early metastasis was observed in this study, longer followup in larger cohorts is necessary to determine the impact of scheduled biopsy omission on these adverse outcomes.

Validation of the Kattan Nomogram for Prostate Cancer Recurrence After Radical Prostatectomy.

BACKGROUND: The Kattan postoperative radical prostatectomy (RP) nomogram is used to predict biochemical recurrence-free progression (BCRFP) after RP. However, external validation among contemporary patients using modern outcome definitions is limited. METHODS: A total of 1,931 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 (median follow-up, 47 months; range, 0-244 months) were assessed for NCCN-defined biochemical failure (BF) and RPCI-defined treatment failure (TF). Actual rates of biochemical failure-free survival (BFS; defined as 1 - BF) and treatment failure-free survival (TFS; defined as 1 - TF) were compared with Kattan BCRFP nomogram predictions. RESULTS: The Kattan BCRFP nomogram predictions at 5 and 10 years were predictive of BFS (area under the receiver operating characteristic curve [AUC], 0.772) and TFS (AUC, 0.774). The Kattan BCRFP nomogram tended to underestimate BFS and TFS compared with actual outcomes. The Kattan 5-year BCRFP predictions consistently overestimated actual 5-year BFS outcomes among subgroups of high- and intermediate-risk patients with at least 5-year outcomes. CONCLUSIONS: The Kattan BCRFP nomogram is a robust predictor of NCCN-defined BF in a large sample of patients with RP with substantial follow-up and modern, standardized failure definitions.

Minimally invasive cytoreductive nephrectomy: a multi-institutional experience.

PURPOSE: To analyze the functional and oncologic outcomes of minimally invasive cytoreductive nephrectomy (CN) in three high-volume cancer centers. PATIENTS AND METHODS: Three prospectively maintained, IRB-approved kidney surgery databases were queried from three high-volume cancer centers. All patients who underwent minimally invasive surgery (laparoscopic, hand-assisted laparoscopic, or robotic) partial or radical CN with existing measurable extra-renal metastatic disease between May 2001 and May of 2013 were included in this analysis. RESULTS: We identified 120 patients who underwent minimally invasive CN for metastatic renal cell carcinoma. Most of the surgeries were radical (93.3 %) and performed laparoscopically (96.6 %). Median operative time was 210 min, with a median estimated blood loss of 150 cc, and 11 (9.2 %) patients received blood transfusions. Four (3.3 %) patients were converted to open surgery due to locally advanced disease and/or bleeding. Postoperative complications were seen in 28 (23.3 %) patients, of which 20 (71.4 %) were classified as minor (Clavien-Dindo I-II). The median survival of the entire cohort was 25.7 months, with a 3-year survival rate of 35 %. Multivariate analysis indicated that only hypertension, brain metastasis, and pT stage were independently associated with worse overall survival (HR > 1). CONCLUSIONS: Minimally invasive cytoreductive nephrectomy is feasible and safe in experienced hands with acceptable morbidity and oncological outcomes.

Comparative Analysis of Smoking as a Risk Factor among Renal Cell Carcinoma Histological Subtypes.

PURPOSE: Smoking is the best established modifiable risk factor for renal cell carcinoma. However, the risks of individual renal cell carcinoma histological subtypes are unknown. Therefore, we investigated the relationship between smoking and renal cell carcinoma subtype. MATERIALS AND METHODS: Cigarette smoking data were prospectively collected from 816 consecutive patients with nonfamilial renal cell carcinoma (705) or benign pathology (111) undergoing nephrectomy at a single National Comprehensive Cancer Network® cancer center, and were retrospectively tested for an association with histological diagnosis on univariable and propensity adjusted analyses. RESULTS: Smoking was reported by 51% of patients, including 21% active smokers and 30% former smokers. Active smoking was more common with clear cell (23%) or papillary (26%) renal cell carcinoma than benign histology (14%, p <0.05 each), yet strikingly less common with chromophobe renal cell carcinoma (6%, p <0.05 vs clear cell or papillary). Any smoking history (active or former) was also relatively uncommon with chromophobe (26%) vs clear cell (53%, p = 0.003) or papillary (58%, p = 0.001) histology. Smoking extent based on mean pack-years was significantly greater with clear cell (15.3 mean pack-years) or papillary (15.2 mean pack-years) renal cell carcinoma but not chromophobe renal cell carcinoma (9.4 mean pack-years) compared to benign histology (9.4 mean pack-years, p ≤0.05, p <0.05, p = 1.0, respectively). On propensity analyses adjusting for multiple variables, clear cell (OR 2.2, p <0.05) and papillary (OR 2.4, p <0.05) histologies but not chromophobe histology remained independently associated with active smoking. CONCLUSIONS: Traditional understanding of smoking as a renal cell carcinoma risk factor applies to clear cell and papillary renal cell carcinoma but not the chromophobe subtype. These findings underscore distinct carcinogenic mechanisms underlying the various renal cell carcinoma subtypes.

Gleason 6 Prostate Cancer: Translating Biology into Population Health.

PURPOSE: Gleason 6 (3+3) is the most commonly diagnosed prostate cancer among men with prostate specific antigen screening, the most histologically well differentiated and is associated with the most favorable prognosis. Despite its prevalence, considerable debate exists regarding the genetic features, clinical significance, natural history, metastatic potential and optimal management. MATERIALS AND METHODS: Members of the Young Urologic Oncologists in the Society of Urologic Oncology cooperated in a comprehensive search of the peer reviewed English medical literature on Gleason 6 prostate cancer, specifically focusing on the history of the Gleason scoring system, histological features, clinical characteristics, practice patterns and outcomes. RESULTS: The Gleason scoring system was devised in the early 1960s, widely adopted by 1987 and revised in 2005 with a more restrictive definition of Gleason 6 disease. There is near consensus that Gleason 6 meets pathological definitions of cancer, but controversy about whether it meets commonly accepted molecular and genetic criteria of cancer. Multiple clinical series suggest that the metastatic potential of contemporary Gleason 6 disease is negligible but not zero. Population based studies in the U.S. suggest that more than 90% of men newly diagnosed with prostate cancer undergo treatment and are exposed to the risk of morbidity for a cancer unlikely to cause symptoms or decrease life expectancy. Efforts have been proposed to minimize the number of men diagnosed with or treated for Gleason 6 prostate cancer. These include modifications to prostate specific antigen based screening strategies such as targeting high risk populations, decreasing the frequency of screening, recommending screening cessation, incorporating remaining life expectancy estimates, using shared decision making and novel biomarkers, and eliminating prostate specific antigen screening entirely. Large nonrandomized and randomized studies have shown that active surveillance is an effective management strategy for men with Gleason 6 disease. Active surveillance dramatically reduces the number of men undergoing treatment without apparent compromise of cancer related outcomes. CONCLUSIONS: The definition and clinical relevance of Gleason 6 prostate cancer have changed substantially since its introduction nearly 50 years ago. A high proportion of screen detected cancers are Gleason 6 and the metastatic potential is negligible. Dramatically reducing the diagnosis and treatment of Gleason 6 disease is likely to have a favorable impact on the net benefit of prostate cancer screening.

External validation of preoperative and postoperative nomograms for prediction of cancer-specific survival, overall survival and recurrence after robot-assisted radical cystectomy for urothelial carcinoma of the bladder.

OBJECTIVE: To externally validate currently available bladder cancer nomograms for prediction of all-cause survival (ACS), cancer-specific survival (CSS), other-cause mortality (OCM) and progression-free survival (PFS). PATIENTS AND METHODS: Retrospective analysis of a prospectively maintained database of 282 patients who underwent robot-assisted radical cystectomy (RARC) at a single institution was performed. The Bladder Cancer Research Consortium (BCRC), International Bladder Cancer Nomogram Consortium (IBCNC) and Lughezzani nomograms were used for external validation, and evaluation for accuracy at predicting oncological outcomes. The 2- and 5-year oncological outcomes were compared, and nomogram performance was evaluated through measurement of the concordance (c-index) between nomogram-derived predicted oncological outcomes and observed oncological outcomes. RESULTS: The median (range) patient age was 70 (36-90) years. At a mean follow-up of 20 months, local or distant disease recurrence developed in 30% of patients. With an overall mortality rate of 33%, 17% died from bladder cancer. The actuarial 2- and 5-year PFS after RARC was 62% (95% confidence interval [CI] 54-68) and 55% (95% CI 46-63), respectively. The actuarial 2- and 5-year ACS was 66% (95% CI 59-72) and 47% (95% CI 37-55), respectively, and the 2- and 5-year CSS was 81% (95% CI 74-86) and 67% (95% CI 57-76), respectively. The PFS c-index for IBCNC was 0.70 at 5 years, and for BCRC was 0.77 at both the 2 and 5 years. The accuracy of ACS and CSS prediction was evaluated using the BCRC and Lughezzani nomograms. Using the BCRC nomogram, c-indices of for 2- and 5-year ACS were each 0.73 and c-indices for 2- and 5-year CSS were 0.70 each. The performance of Lughezzani nomogram for 5-year ACS, cancer-specific mortality and OCM were 0.73, 0.72 and 0.40, respectively. The BCRC nomogram prediction of advanced pathological stage and lymph node metastasis was modest, with c-indices of 0.66 and 0.61, respectively. CONCLUSIONS: Bladder cancer nomograms available from the current open RC literature adequately predict ACS, CSS and PFS after RARC. However, prediction of advanced tumour stage and lymph node metastasis was modest and the Lughezzani nomogram failed to predict OCM.

Efficacy of robot-assisted radical cystectomy (RARC) in advanced bladder cancer: results from the International Radical Cystectomy Consortium (IRCC).

OBJECTIVE: To characterise the surgical feasibility and outcomes of robot-assisted radical cystectomy (RARC) for pathological T4 bladder cancer. PATIENTS AND METHODS: Retrospective evaluation of a prospectively maintained International Radical Cystectomy Consortium database was conducted for 1118 patients who underwent RARC between 2003 and 2012. We dichotomised patients based on pathological stage (≤pT3 vs pT4) and evaluated demographic, operative and pathological variables in relation to morbidity and mortality. RESULTS: In all, 1000 ≤pT3 and 118 pT4 patients were evaluated. The pT4 patients were older than the ≤pT3 patients (P = 0.001). The median operating time and blood loss were 386 min and 350 mL vs 396 min and 350 mL for p T4 and ≤pT3, respectively. The complication rate was similar (54% vs 58%; P = 0.64) among ≤pT3 and pT4 patients, respectively. The overall 30- and 90-day mortality rate was 0.4% and 1.8% vs 4.2% and 8.5% for ≤pT3 vs pT4 patients (P < 0.001), respectively. The body mass index (BMI), American Society of Anesthesiology score, length of hospital stay (LOS) >10 days, and 90-day readmission were significantly associated with complications in pT4 patients. Meanwhile, BMI, LOS >10 days, grade 3-5 complications, 90-day readmission, smoking, previous abdominal surgery and neoadjuvant chemotherapy were significantly associated with mortality in pT4 patients. On multivariate analysis, BMI was an independent predictor of complications in pT4 patients, but not for mortality. CONCLUSIONS: RARC for pT4 bladder cancer is surgically feasible but entails significant morbidity and mortality. BMI was independent predictor of complications in pT4 patients.

Differential effects of obesity on perioperative outcomes in renal cell carcinoma patients based on race and ethnicity and neighborhood-level socioeconomic status.

Background: Obesity is a well-established risk factor of renal cell carcinoma (RCC), however the impact of obesity on surgical outcomes for racial and ethnic minority patients with RCC is unclear. This study investigated whether a higher body mass index (BMI) or obesity (BMI ≥30 kg/m2) was associated with worse perioperative outcomes and if there were heterogeneous effects based on race, ethnicity, and neighborhood-level socioeconomic factor. Methods: In this single-center cross-sectional study, medical records of patients who underwent partial or radical nephrectomy between 2010 and 2022 were retrospectively reviewed. Logistic regression analysis was performed to assess associations of BMI and perioperative outcomes [ischemia time, estimated blood loss (EBL), and length of hospital stay]. Results: A total of 432 patients, including 49.8% non-Hispanic White (NHW), 35.0% Hispanic, and 6.9% American Indian (AI) patients, were included. Median [interquartile range (IQR)] BMI was 30.2 (26.3-35.2) kg/m2, and Hispanic (31.5) and AI (32.5) patients had higher median BMI than NHW (29.1) patients (P=0.006). Median ischemia time, EBL, and length of hospital stay were 18.5 (IQR, 15.0-22.4) minutes, 150 (IQR, 75.0-300.0) mL, and 3 (IQR, 2-5) days. BMI ≥35 kg/m2 was associated with a longer ischemia time [>18.5 minutes; odds ratio (OR), 5.17; 95% confidence interval (CI): 1.81-14.76; P=0.002], and the association was stronger in NHW than Hispanic patients (BMI continuous OR, 1.13; 95% CI: 1.04-1.22; P=0.004 in NHW and OR, 1.07; 95% CI: 0.98-1.17; P=0.12 in Hispanics). Class I and II/III obese patients had over two-fold increased odds of a larger EBL (>150 mL) than patients with normal weight (OR, 2.17; 95% CI: 1.03-4.59; P=0.04 for class I and OR, 2.24; 95% CI: 1.04-4.84; P=0.04 for class II/III obese patients). This association was stronger in patients from neighborhoods with high social deprivation index (SDI) and in NHW patients (BMI ≥30 vs. <30 kg/m2, OR, 3.53; 95% CI: 1.57-7.97; P=0.002 in high SDI neighborhoods and OR, 2.38; 95% CI: 1.10-5.14; P=0.03 in NHW). BMI was not associated with a longer hospital stay. Conclusions: In this study, obesity increased likelihood of worse perioperative outcomes, and the associations varied based on race and ethnicity and neighborhood-level socioeconomic factors.