A contemporary comparison of laparoscopic versus open partial nephrectomy for renal cell carcinoma.

PURPOSE: To analyze surgical and oncologic outcomes of patients undergoing open partial nephrectomy (OPN) versus laparoscopic partial nephrectomy (LPN) for treatment of renal cell carcinoma (RCC). METHODS: We retrospectively investigated our institutional RCC database for patients who underwent PN for RCC from 1997 to 2018. Decision for technique was at the discretion of the operating urologist, following practice patterns and training history. Outcomes analyzed included pre/peri/post-operative parameters, pathologic outcomes, and disease recurrence rates. RESULTS: 1088 patients underwent PN from 1997 to 2018. After exclusionary criteria, 631 patients who underwent 647 unique PNs for a total of 162 OPN and 485 LPN remained. Baseline, pre-op, and pathologic characteristics were not statistically different. Surgical time was lower in laparoscopic cases [185 vs. 205 min] (p = 0.013). Margin involvement was not statistically different; LPN had lower estimated blood loss (EBL) [150 vs. 250 mL] (p < 0.001) and longer ischemia time [21 vs. 19 min] (p = 0.005). LPN had shorter length of stay [2 vs. 4 days] (p < 0.001), fewer overall complications (p < 0.001), and no significant difference in high-grade complications [2.89 vs. 4.32%] (p = 0.379). Fewer LPN patients developed metastases [1.65 vs. 4.94%] (p = 0.0499). Local recurrence rates were not statistically different [1.24 vs. 3.09%] (p = 0.193). Renal function was equivalent between cohorts post-operatively. CONCLUSION: Long-term oncologic outcomes were not significantly different between LPN versus OPN, with no statistical difference in patient and tumor characteristics. LPN was associated with lower EBL, shorter length of stay, and lower overall complication risk. Renal function was not significantly different between cohorts.

Impact of an Expanded Definition of Family History on Outcomes of Active Surveillance for Prostate Cancer.

PURPOSE: Despite family history being an established risk factor for prostate cancer, the role of a broader definition of family history inclusive of not just prostate cancer but other genetically related malignancies has not been investigated in the active surveillance population. Here, we evaluate the impact of an expanded definition of family history on active surveillance outcomes. MATERIALS AND METHODS: Patients undergoing active surveillance for prostate cancer at Massachusetts General Hospital from 1997-2019 with detailed data available on family cancer history were identified. Primary outcome was biopsy progression-free survival, and secondary outcomes were treatment-free survival, adverse pathological features at prostatectomy, and biochemical recurrence after treatment. Statistical analyses were conducted using the Kaplan-Meier method and Cox regression. RESULTS: Among 855 evaluable patients, 300 (35.1%) patients had any family history of prostate cancer, and 95 (11.1%) had a family history of related malignancies suggestive of a hereditary cancer syndrome. Family history of prostate cancer alone was not associated with biopsy progression, whereas family history suggestive of a hereditary cancer syndrome was associated with a significantly increased risk of biopsy progression (HR 1.43, 95%CI 1.01-2.02), independent of other known clinicopathological risk factors in multivariable analysis. Similarly, family history suggestive of a hereditary cancer syndrome was associated with significantly lower treatment-free survival (HR 1.58, 95%CI 1.14-2.18) in multivariable analysis. No significant association was found between family history and adverse features on surgical pathology or biochemical recurrence. CONCLUSIONS: An expanded family history suggestive of a hereditary cancer syndrome is an independent predictor of biopsy progression during active surveillance. Men with such a family history may still be offered active surveillance but should be counseled regarding the higher risk of disease progression.

Differentiation of patients with and without prostate cancer using urine 1 H NMR metabolomics.

Prostate cancer (PCa) is one of the most prevalent cancers in men worldwide. For its detection, serum prostate-specific antigen (PSA) screening is commonly used, despite its lack of specificity, high false positive rate, and inability to discriminate indolent from aggressive PCa. Following increases in serum PSA levels, clinicians often conduct prostate biopsies with or without advanced imaging. Nuclear magnetic resonance (NMR)-based metabolomics has proven to be promising for advancing early-detection and elucidation of disease progression, through the discovery and characterization of novel biomarkers. This retrospective study of urine-NMR samples, from prostate biopsy patients with and without PCa, identified several metabolites involved in energy metabolism, amino acid metabolism, and the hippuric acid pathway. Of note, lactate and hippurate-key metabolites involved in cellular proliferation and microbiome effects, respectively-were significantly altered, unveiling widespread metabolomic modifications associated with PCa development. These findings support urine metabolomics profiling as a promising strategy to identify new clinical biomarkers for PCa detection and diagnosis.

Complications and Outcomes of Salvage Cystectomy after Trimodality Therapy.

PURPOSE: Salvage cystectomy is required for some patients with intravesical recurrence after trimodality therapy. We compared postoperative outcomes between salvage cystectomy post-trimodality therapy, primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. MATERIALS AND METHODS: We included 265 patients who underwent radical cystectomy at Massachusetts General Hospital for cT1-T4 bladder cancer between 2003 and 2013. Patients were grouped as salvage cystectomy post-trimodality therapy, primary cystectomy or primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Early (≤90 days) and late (>90 days) complications were compared. Disease-specific survival and overall survival were calculated using a Cox regression model, and adjusted survival curves were generated. RESULTS: The median followup from the time of cystectomy was 65.5 months. There was no difference in intraoperative and early complications between the groups. The detection of late complications was higher in salvage cystectomy post-trimodality therapy compared to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy (p=0.03). In multivariable Cox regression analysis, salvage cystectomy post-trimodality therapy was associated with a higher incidence of any late (HR 2.3, p=0.02) and major late complications (HR 2.1, p <0.05). There was no difference in disease-specific survival (p=0.8) or overall survival (p=0.9) between the groups. CONCLUSIONS: Salvage cystectomy post-trimodality therapy for intravesical recurrence post-trimodality therapy has an intraoperative and early complication rate comparable to primary cystectomy and primary cystectomy with prior history of nontrimodality therapy abdominal or pelvic radiotherapy. Salvage cystectomy post-trimodality therapy is associated with a higher risk of overall and major late complications than primary cystectomy. The disease-specific survival and overall survival of patients who require salvage cystectomy post-trimodality therapy are comparable to both groups.

Characterization of the metabolomic profile of renal cell carcinoma by high resolution magic angle spinning proton magnetic resonance spectroscopy.

BACKGROUND: Renal cell carcinoma (RCC) is a metabolic disease, with subtypes exhibiting aberrations in different metabolic pathways. Metabolomics may offer greater sensitivity for revealing disease biology. We investigated the metabolomic profile of RCC using high-resolution magic angle spinning (HRMAS) proton magnetic resonance spectroscopy (1HMRS). METHODS: Surgical tissue samples were obtained from our frozen tissue bank, collected from radical or partial nephrectomy. Specimens were fresh-frozen, then stored at -80 °C until analysis. Tissue HRMAS-1HMRS was performed. A MatLab-based curve fitting program was used to process the spectra to produce relative intensities for 59 spectral regions of interest (ROIs). Comparisons of the metabolomic profiles of various RCC histologies and benign tumors, angiomyolipoma, and oncocytoma, were performed. False discovery rates (FDR) were used from the response screening to account for multiple testing; ROIs with FDR p < 0.05 were considered potential predictors of RCC. Wilcoxon rank sum test was used to compare median 1HMRS relative intensities for those metabolites that may differentiate between RCC and benign tumor. Logistic regression determined odds ratios for risk of malignancy based on the abundance of each metabolite. RESULTS: Thirty-eight RCC (16 clear cell, 11 papillary, 11 chromophobe), 10 oncocytomas, 7 angiomyolipomas, and 13 adjacent normal tissue specimens (matched pairs) were analyzed. Candidate metabolites for predictors of malignancy based on FDR p-values include histidine, phenylalanine, phosphocholine, serine, phosphocreatine, creatine, glycerophosphocholine, valine, glycine, myo-inositol, scyllo-inositol, taurine, glutamine, spermine, acetoacetate, and lactate. Higher levels of spermine, histidine, and phenylalanine at 3.15 to 3.13 parts per million (ppm) were associated with decreased risk of RCC (OR 4 × 10-5, 95% CI 7.42 × 10-8, 0.02), while 2.84 to 2.82 ppm increased the risk of malignant pathology (OR 7158.67, 95% CI 6.3, 8.3 × 106). The specific metabolites characterizing this region remain to be identified. Tumor stage did not affect metabolomic profile of malignant tumors, suggesting that metabolites are dependent on histologic subtype. CONCLUSIONS: HRMAS-1HMRS identified metabolites that may predict RCC. We demonstrated that those in the 3.14 to 3.13 ppm ROI were present in lower levels in RCC, while higher levels of metabolites in the 2.84 to 2.82 ppm ROI were associated with substantially increased risk of RCC. Further research in a larger population is required to validate these findings.

Impact of a negative confirmatory biopsy on risk of disease progression among men on active surveillance for prostate cancer.

OBJECTIVE: Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity. METHODS: We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression. RESULTS: We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34-0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment. CONCLUSIONS: A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS.

A Scoping Review of the Economic Burden of Non-Cancerous Genitourinary Conditions.

OBJECTIVE: To provide a scoping review of the economic burden of non-cancerous genitourinary conditions (NCGUC). METHODS: A scoping review of the economic costs associated with NCGUC was conducted for literature published between 1990-2020. The articles were screened and relevant articles were selected for review. These articles were abstracted with information pertaining to the costs surrounding NCGUC. A descriptive analysis of the data was conducted. RESULTS: We found 3,298 articles in our scoping review. Of these, we found 39 relevant articles related to pelvic floor dysfunction and pelvic organ prolapse, interstitial cystitis, neurogenic bladder, nocturia, urinary tract infections, urolithiasis, urinary incontinence, benign prostatic hyperplasia, overactive bladder, and erectile dysfunction of which the data was reviewed. CONCLUSION: Although the data in estimating the economic burden is limited, existing evidence demonstrates a significant component of health care spending on NCGUC. Much of the spending is out-of-pocket and indirect costs that are difficult to measure which may increase the magnitude of the costs. There is a need for future research that takes a holistic look at the economic impact of NCGUC.

A machine learning approach to predict progression on active surveillance for prostate cancer.

PURPOSE: Robust prediction of progression on active surveillance (AS) for prostate cancer can allow for risk-adapted protocols. To date, models predicting progression on AS have invariably used traditional statistical approaches. We sought to evaluate whether a machine learning (ML) approach could improve prediction of progression on AS. PATIENTS AND METHODS: We performed a retrospective cohort study of patients diagnosed with very-low or low-risk prostate cancer between 1997 and 2016 and managed with AS at our institution. In the training set, we trained a traditional logistic regression (T-LR) classifier, and alternate ML classifiers (support vector machine, random forest, a fully connected artificial neural network, and ML-LR) to predict grade-progression. We evaluated model performance in the test set. The primary performance metric was the F1 score. RESULTS: Our cohort included 790 patients. With a median follow-up of 6.29 years, 234 developed grade-progression. In descending order, the F1 scores were: support vector machine 0.586 (95% CI 0.579 - 0.591), ML-LR 0.522 (95% CI 0.513 - 0.526), artificial neural network 0.392 (95% CI 0.379 - 0.396), random forest 0.376 (95% CI 0.364 - 0.380), and T-LR 0.182 (95% CI 0.151 - 0.185). All alternate ML models had a significantly higher F1 score than the T-LR model (all p <0.001). CONCLUSION: In our study, ML methods significantly outperformed T-LR in predicting progression on AS for prostate cancer. While our specific models require further validation, we anticipate that a ML approach will help produce robust prediction models that will facilitate individualized risk-stratification in prostate cancer AS.

Evaluation of In-Office MRI/US Fusion Transperineal Prostate Biopsy via Free-hand Device during Routine Clinical Practice.

OBJECTIVES: To describe our recent experience with in-office transperineal prostate biopsy, including the adoption of software-assisted MRI/US fusion technology. Technological improvements have recently allowed transperineal biopsy to be effectively integrated into outpatient practices with negligible risk of infection. METHODS: We retrospectively reviewed a cohort of men undergoing transperineal prostate biopsy from 2018-2020, at a single institution. We compared this to another cohort of men undergoing transrectal fusion biopsy from 2014-2018, matched to the first cohort based on age, PSA, and presence of prostate cancer diagnosis prior to biopsy. All patients underwent systematic transperineal templated biopsies in addition to fusion biopsies of MRI-visible lesions. Baseline characteristics, MRI findings, biopsy results, and complications were analyzed and compared between the 2 groups. RESULTS: One-hundred and thirty men underwent transperineal prostate biopsy, and 130 men underwent transrectal fusion biopsy. Of those who underwent transperineal biopsy, 30% underwent fusion biopsy while all men with the transrectal biopsy underwent fusion biopsy. Men who underwent transperineal vs transrectal biopsy demonstrated lower infection rates (0% vs 0.8%, P = .31) with fewer prophylactic antibiotics prescribed at provider's discretion (48% vs 100%), yet higher total post-biopsy complication rates (6.1% vs 0.8%, P = .036). CONCLUSION: Our initial experiences with transperineal prostate biopsy confirm prior findings demonstrating feasibility in outpatient urologic practice without infectious complication. Software-assisted MRI/US fusion technology can be successfully integrated with transperineal biopsies to target suspicious lesions. Higher rates of non-infectious complications were observed compared with transrectal biopsy. Further analysis is needed to determine whether risk profiles improve over the learning curve of this newly implemented approach.

Percutaneous Biopsy Tract Seeding in a Patient with Muscle-invasive Bladder Cancer.

Percutaneous biopsy can be used for tissue diagnosis of bladder tumors when cystoscopy with transurethral resection is not possible. The largest known case series includes 15 patients with no reported complications and good concordance with surgical pathology. However, concern remains regarding exposure of nonurothelial surfaces to tumor cells, as there are rare documented cases of tumor seeding along nephrostomy and biopsy tracts in upper tract urothelial carcinoma (UC). We present the first documented human case of bladder cancer involvement of the omentum and peritoneum along a biopsy tract and review the use of percutaneous access for upper and lower tract UC.