MRI-based radiomic features for identifying recurrent prostate cancer after proton radiation therapy.

PURPOSE: Magnetic Resonance Imaging (MRI) evaluation of recurrent prostate cancer (PCa) following proton beam therapy is challenging due to radiation-induced tissue changes. This study aimed to evaluate MRI-based radiomic features so as to identify the recurrent PCa after proton therapy. METHODS: We retrospectively studied 12 patients with biochemical recurrence (BCR) following proton therapy. Two experienced radiologists identified prostate lesions from multi-parametric MRI (mpMRI) images post-proton therapy and marked control regions of interest (ROIs) on the contralateral side of the prostate gland. A total of 210 radiomic features were extracted from lesions and control regions on the T2-weighted (T2WI) and Apparent Diffusion Coefficient (ADC) image series. Recursive Feature Elimination with Cross-Validation method (RFE-CV) was used for feature selection. A Multilayer Perceptron (MLP) neural network was developed to classify three classes: cancerous, benign, and healthy tissue. The 12-core biopsy results were used as the gold standard for the segmentations. The classifier performance was measured using specificity, sensitivity, the area under receiver operating characteristic curve (AUC), and other statistical indicators. RESULTS: Based on biopsy results, 10 lesions were identified as PCa recurrence while eight lesions were confirmed to be benign. Ten radiomic features (10/210) were selected to build the multi-class classifier. The radiomics classifier gave an accuracy of 0.83 in identifying cancerous, benign, and healthy tissue with a sensitivity of 0.80 and specificity of 0.85. The model yielded an AUC of 0.87, 95% CI [0.72-1.00] in differentiating cancer from the benign and healthy tissues. CONCLUSIONS: Our proof-of-concept study demonstrates the potential of using radiomic features as part of the differential diagnosis of PCa on mpMRI following proton therapy. The results need to be validated in a larger cohort.

The geriatric nutritional risk index predicts complications after nephrectomy for renal cancer.

PURPOSE: We examined if malnutrition, as defined by the Geriatric Nutritional Risk Index (GNRI), is independently associated with 30-day postoperative complications in patients undergoing nephrectomy for the treatment of renal cancer. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database from 2006-2019, we identified patients ≥65 years old who underwent nephrectomy for renal cancer. The following formula for GNRI was used to define preoperative nutritional status: 1.489 x serum albumin (g/L) + 41.7 x (current body weight [kg]/ ideal body weight [kg]). Based on the GNRI, patients were classified as having no (> 98), moderate (92-98), or severe malnutrition (< 92). After adjusting for potential confounders, multivariable logistic regression analyses were performed to assess the association between GNRI and 30-day postoperative complications. Odds ratios (OR) with 95% confidence intervals (CI) were reported. RESULTS: A total of 7,683 patients were identified, of which 1,241 (16.2%) and 872 (11.3%) had moderate and severe malnutrition, respectively. Compared to normal nutrition, moderate and severe malnutrition were significantly associated with a greater odds of superficial surgical site infection, progressive renal insufficiency, readmission, extended length of stay, and non-home discharge. Severe malnutrition was also associated with urinary tract infection (OR 2.10, 95% CI 1.31-3.35) and septic shock (OR 2.93, 95% CI 1.21-7.07). CONCLUSION: Malnutrition, as defined by a GNRI ≤ 98, is an independent predictor of 30-day complications following nephrectomy. The GNRI could be used to counsel elderly patients with renal cancer prior to nephrectomy.

The Geriatric Nutritional Risk Index Predicts Postoperative Outcomes in Bladder Cancer: A Propensity Score-Matched Analysis.

PURPOSE: The Geriatric Nutritional Risk Index (GNRI) is a simple screening tool to predict nutrition-related risk of morbidity and mortality in older patients. We assessed whether preoperative GNRI was associated with 30-day complications after radical cystectomy (RC). MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified patients 65 years or older who underwent RC for the treatment of bladder cancer between 2007 and 2019. Patients were dichotomized into at-risk (GNRI ≤98) or no-risk (GNRI >98) groups. Using propensity score matching, the 2 groups were compared for baseline differences and 30-day outcomes. We evaluated GNRI as an independent predictor of postoperative complications using multivariable logistic regression analysis. RESULTS: We identified 2,926 patients eligible for analysis. After propensity score matching, patients in the at-risk GNRI group had higher rates of any complication (p=0.017), blood transfusion (p=0.002), extended length of stay (p=0.004) and nonhome discharge (p <0.001). Multivariable logistic regression analysis revealed that a decreasing GNRI is an independent prognostic factor for mortality (OR 1.05, 95% CI 1.01-1.08, p=0.009), blood transfusion (OR 1.03, 95% CI 1.02-1.04, p <0.001), pneumonia (OR 1.04, 95% CI 1.01-1.07, p=0.013), extended length of stay (OR 1.03, 95% CI 1.02-1.05, p <0.001) and nonhome discharge (OR 1.04, 95% CI 1.03-1.06, p <0.001). CONCLUSIONS: We demonstrate that nutritional status evaluated by GNRI predicts 30-day complications after RC.

Combination therapy in metastatic castration sensitive prostate cancer: A Systematic review and network meta-analysis.

Introduction: Studies directly comparing the different combination therapies offered to men with metastatic castration sensitive prostate cancer (mCSPC), are not available yet. This study was designed using the network meta-analysis (NMA) framework to provide a comparison of the different available options for the treatment of men with mCSPC. Methods: A systematic search was performed and the prospective randomized controlled trials reporting the overall survival (OS) or failure-free survival (FFS) were selected for review. A total of 14 studies were included in the NMA. Results: The addition of abiraterone, apalutamide, docetaxel, and docetaxel with zoledronic acid to the androgen deprivation therapy (ADT) demonstrated a significant improvement in the OS. In indirect comparison, abiraterone had a higher impact on the OS as compared to docetaxel (hazard ratio [HR]: 1.21, 95% confidence interval [CI]: 1.0-1.46) and docetaxel with zoledronic acid (HR: 1.31, 95% CI: 1.05-1.63) but not apalutamide. Furthermore, apalutamide was not different than docetaxel or docetaxel with zoledronic acid. There was a significant improvement in the FFS with the combination of abiraterone, apalutamide, docetaxel (HR: 0.61, 95% CI: 0.46-0.81), docetaxel with zoledronic acid (HR: 0.62, 95% CI: 0.43-0.9), and enzalutamide (HR: 0.39, 95% CI: 0.25-0.61) as compared to the ADT alone. Similar to the indirect comparison of OS, abiraterone outperformed docetaxel (HR: 1.66, 95% CI: 1.12-2.47), docetaxel with zoledronic acid (HR: 1.69, 95% CI: 1.06-2.68), and enzalutamide (HR: 1.06, 95% CI: 0.63-1.80), but not apalutamide in terms of impact on the FFS. Conclusion: Overall, abiraterone demonstrated better OS and FFS outcomes as compared to all the other combination strategies in this NMA.

Percutaneous ablative cryoimmunotherapy for micrometastaic abscopal effect: No complications.

Recent studies have shown efficacy of nivolumab, a monoclonal antibody specific for an immunoregulatory protein termed programmed death 1 (PD-1), against metastatic renal cell carcinoma. PD-1 is a transmembrane protein expressed on T cells that suppresses activation upon binding to its ligands, which may be secreted paraneoplastically by various cancers. Inhibition of PD-1 signaling via nivolumab may sensitize tumor-specific T lymphocytes in the immunosuppressive tumor microenvironment. Systemic elimination of micrometastases requires robust activation and proliferation of tumor antigen stimulated T cells. Cryoablation lyses tumor cell membranes but leaves intracellular tumor antigens intact for recognition by effectors systemically, while eliminating permissive T cell subtypes locally. This single case report describes CT-guided percutaneous cryoablation of a metastatic renal cell carcinoma with local administration of nivolumab to simultaneously debulk the primary tumor, sensitize effector T cells against tumor antigens, and augment the systemic immune response elicited against established metastases. One month follow up PET scan revealed decreased uptake in the two smaller metastatic bone lesions with the smallest lesion completely eliminated. The largest metastatic bone lesion was slightly decreased in size and exhibited slightly increased uptake. The patient's presenting complaint of hip pain was abrogated, allowing her to resume independent ambulation. CT-guided percutaneous cryoablation is minimally invasive and preserves tumor antigens, which are subsequently presented to tumor-specific T cells; their differentiation into cytotoxic T cells may be guided and their proliferation may be augmented by local administration of immunostimulatory pharmacotherapy at the time of the procedure.

Decipher test impacts decision making among patients considering adjuvant and salvage treatment after radical prostatectomy: Interim results from the Multicenter Prospective PRO-IMPACT study.

BACKGROUND: Patients with prostate cancer and their providers face uncertainty as they consider adjuvant radiotherapy (ART) or salvage radiotherapy (SRT) after undergoing radical prostatectomy. The authors prospectively evaluated the impact of the Decipher test, which predicts metastasis risk after radical prostatectomy, on decision making for ART and SRT. METHODS: A total of 150 patients who were considering ART and 115 who were considering SRT were enrolled. Providers submitted a management recommendation before processing the Decipher test and again at the time of receipt of the test results. Patients completed validated surveys on prostate cancer (PCa)-specific decisional effectiveness and PCa-related anxiety. RESULTS: Before the Decipher test, observation was recommended for 89% of patients considering ART and 58% of patients considering SRT. After Decipher testing, 18% (95% confidence interval [95% CI], 12%-25%) of treatment recommendations changed in the ART arm, including 31% among high-risk patients; and 32% (95% CI, 24%-42%) of management recommendations changed in the salvage arm, including 56% among high-risk patients. Decisional Conflict Scale (DCS) scores were better after viewing Decipher test results (ART arm: median DCS before Decipher, 25 and after Decipher, 19 [P<.001]; SRT arm: median DCS before Decipher, 27 and after Decipher, 23 [P<.001]). PCa-specific anxiety changed after Decipher testing; fear of PCa disease recurrence in the ART arm (P = .02) and PCa-specific anxiety in the SRT arm (P = .05) decreased significantly among low-risk patients. Decipher results reported per 5% increase in 5-year metastasis probability were associated with the decision to pursue ART (odds ratio, 1.48; 95% CI, 1.19-1.85) and SRT (odds ratio, 1.41; 95% CI, 1.09-1.81) in multivariable logistic regression analysis. CONCLUSIONS: Knowledge of Decipher test results was associated with treatment decision making and improved decisional effectiveness among men with PCa who were considering ART and SRT. Cancer 2017;123:2850-59. © 2017 American Cancer Society.

Does care fragmentation in patients with bladder cancer lead to worse outcomes?

INTRODUCTION: Care fragmentation may influence oncologic outcomes. The impact of care fragmentation on the outcomes of patients receiving neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) for muscle-invasive bladder cancer (MIBC) is not well defined. We aimed to compare outcomes between patients who received fragmented care (FC) versus non-fragmented care (NFC). METHODS: The National Cancer Database was queried for adult (≥18 years old) patients with cT2-T4aN0M0 urothelial carcinoma of the bladder receiving NAC followed by RC between 2004 and 2017. Patients were dichotomized based on whether they received FC (defined as receiving NAC at a different facility from where RC was performed) or NFC (defined as receiving NAC and RC at a single facility). The main outcome of interest was overall survival (OS). Secondary outcomes included time from diagnosis to treatment (NAC and RC) and perioperative outcomes. Kaplan-Meier survival estimates were calculated after stratifying by type of care received. Multivariable Cox regression analysis was performed to evaluate the association between FC and OS in the context of other clinically relevant covariates. RESULTS: A total of 2223 patients were included: 1035 (46.6%) received FC whereas 1188 (53.4%) received NFC. Factors associated with FC included greater travel distance, higher comorbidity burden, and surgical treatment at a high-volume facility. Patients who received FC had a slightly longer median time to RC (160 vs. 154 days, P = 0.001). However, on Kaplan-Meier analysis no differences in median OS were found between the two groups. On multivariable Cox regression analysis, factors associated with worse OS included age, advanced TNM stage, lymphovascular invasion, and positive surgical margins; yet FC was not associated with worse OS (hazard ratio [HR] 1.02; 95% confidence interval [CI] 0.88-1.17). On subgroup analysis, we found that FC received at academic facilities (HR 0.76; 95% CI 0.58-0.99), as well as NFC received at high-volume centers (HR 0.65; 95% CI 0.43-0.98), were associated with a decrease in overall mortality. CONCLUSIONS: Fragmented care is not associated with worse survival outcomes in patients with MIBC receiving NAC followed by RC.

Can magnetic resonance imaging differentiate muscle invasion (T2) and lamina propria invasion (T1) urothelial carcinoma of the bladder? A systematic review and meta-analysis of Vesical Imaging-Reporting and Data System accuracy.

Background: Vesical Imaging-Reporting and Data System (VI-RADS) was developed as a structured reporting tool to anticipate the possibility of muscle invasion. This study is aimed to investigate the diagnostic accuracy of VI-RADS for discriminating T2 from T1 bladder cancer. Materials and methods: Scopus, Web of Science, PubMed, and Embase were searched on October 4, 2021, for studies with the following characteristics: (1) bladder cancer patient population, (2) VI-RADS as an index test, (3) retransurethral resection of bladder tumor/cystectomy as a reference, and (4) adequate VI-RADS score data for T1 and T2 lesions. The analyses were performed using the binary regression model of MIDAS in Stata. Results: Six studies with 624 magnetic resonance imaging reports were included. The receiver operating characteristics curve for differentiation of T2 from T1 bladder cancer showed an area under the curve of 0.93 (95% confidence interval [CI], 0.91-0.95) for a VI-RADS ≥3 and 0.75 (95% CI, 0.71-0.79) for a VI-RADS ≥4. A VI-RADS ≥3 showed high sensitivity of 93% (95% CI, 85%-97%), specificity of 61% (95% CI, 30%-86%), positive likelihood ratio of 2.4 (95% CI, 1.1-5.3), and negative likelihood ratio of 0.11 (95% CI, 0.05-0.24). A total of 10.4% of T2 lesions were scored as VI-RADS 2, while 10% of T1 lesions were scored as VI-RADS 4 or 5. Conclusions: The VI-RADS ≥3 has high accuracy and sensitivity for detecting muscle invasion in borderline populations of T1 or T2 bladder cancer. Thus, the VI-RADS could be a good non-invasive screening test for the detection of T2 urothelial lesions.

Magnetic resonance imaging radiomic features for recurrent prostate cancer following proton radiation therapy-A pilot study.

OBJECTIVE: The role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy. METHODS: After obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists. RESULTS: We found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57-79) and median time to biochemical recurrence was 7.3 years (range 3-13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P < 0.001). CONCLUSIONS: Results of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.

Natural history, and impact of surgery and radiation on survival outcomes of men diagnosed with low-grade prostate cancer at ≤ 55 years of age: a 25-year follow-up of > 60,000 men.

PURPOSE: Low-grade prostate cancer has low mortality rates at 10 years; however, it is unclear if the response is sustained for up to 25 years of follow-up. METHODS: Using Surveillance, Epidemiology, and End Results database, the overall and cancer-specific mortality rates were compared among men ≤ 55 years of age diagnosed with low-grade prostate cancer that either had radical prostatectomy, radiotherapy, or no known treatment. RESULTS: Of the 62,772 men diagnosed with low-grade prostate cancer between 1975 and 2016, about 60%, 20% and 20% of men underwent radical prostatectomy, radiotherapy, and no known treatment, respectively. At a median follow-up of 10 years, almost 2% and 7% of men died of prostate cancer and other causes, respectively. The overall mortality was significantly better in radical prostatectomy group compared to no known treatment group (HR 1.99, CI 1.84-2.15, P value < 0.001), but not between the radiotherapy and no known treatment groups. Moreover, the overall and cancer-specific mortality rates in the radiotherapy group were almost two and three times compared to the radical prostatectomy group, respectively (HR 2.15, CI 2.01-2.29, P value < 0.001 for overall mortality and HR 2.87, CI 2.5-3.29, P value < 0.001 for cancer-specific mortality). CONCLUSIONS: The study confirms low mortality rates in men diagnosed with low-grade prostate cancer for over 25 years' follow-up. While radical prostatectomy improves survival significantly compared to no known treatment, radiotherapy is associated with an increase in overall and cancer-specific mortality, which may be related to long-term toxicities.

Extramural venous invasion: a novel magnetic resonance imaging biomarker for adverse pathology in bladder cancer.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

Diagnostic accuracy of vesical imaging-reporting and data system (VI-RADS) in suspected muscle invasive bladder cancer: A systematic review and diagnostic meta-analysis.

OBJECTIVE: To investigate the accuracy of Vesical Imaging-Reporting and Data System (VI-RADS) in detection of muscle-invasive bladder cancer (MIBC) we performed a systematic review and meta-analysis of the available literature. MATERIALS AND METHODS: Scopus, Web of Science, PubMed, and EMBASE were searched up to 8 March 2021 for the studies evaluating the diagnostic performance of VI-RADS for the detection of MIBC. Inclusion criteria were patients with bladder cancer; index test of VI-RADS based on multiparametric MRI; reference test of histopathological findings from TURBT, re-TURBT, or cystectomy and study design of cohort. Case reports, review articles, and editorials were eliminated, as well as studies with insufficient knowledge to acquire TP, FP, FN, and TN values of VI-RADS. The MIDAS module of STATA was for statistical analysis. The heterogeneity was explored using subgroup analysis and meta-regression analysis. RESULTS: Overall, 22 eligible studies, consisting of 2,576 participants and 5,414 MRI reports, were included in this meta-analysis. The area under curve (AUC) of VI-RADS at cut-point values of 3 and 4 were 0.93 (95%CI: 0.91, 0.95), 0.93 (95%CI: 0.90, 0.95), respectively. Based on Youden's J statistic, the optimal VI-RADS cutoff value for predicting MIBC was determined as 3 which granted a pooled sensitivity of 89% (95%CI: 87%, 91%; I2=48%) and a specificity of 84% (95%CI: 80%, 87%; I2=90%). Based on meta-regression, the sources of inter-study heterogeneity for VI-RADS ≥ 3 were the sample size > 70, study design, single-center vs multi-center, patient population characteristics (i.e., gender, age), reference standard, histology, magnetic strength, T2WI slice thickness, and the number of radiologists reporting the MRI results (P value ≤ 0.01). CONCLUSION: The VI-RADS demonstrates consistently high diagnostic accuracy to predict MIBC. This scoring system could be applied in standard staging MRI reports of bladder cancer and can be incorporated into future MIBC work up guidelines.

Inter-reader reliability of the vesical imaging-reporting and data system (VI-RADS) for muscle-invasive bladder cancer: a systematic review and meta-analysis.

To evaluate the diagnostic agreement between readers in VI-RADS interpretation to detect muscle-invasive bladder cancer (MIBC) preoperatively, we conducted a systematic review and meta-analysis of the available data. Scopus, PubMed, Web of Science, and Embase databases were systematically searched up to November 13, 2021. Case reports, review articles, editorials, and studies with insufficient data were eliminated. The Quality Appraisal of the Diagnostic Reliability Checklist was used to assess the risk of bias. The degree of agreement was determined by Cohen's kappa coefficient (κ) for comparison of data. The heterogeneity of these studies was explored using subgroup analysis and meta-regression analysis. The level of confidence was set at 0.05. All analyses were conducted in STATA 16.0. Overall, 19 eligible studies, consisting of 2439 participants, were included in this meta-analysis. The inter-reader agreement for VI-RADS in MIBC detection ranged from κ of 0.45 to 0.96 among included studies. The pooled inter-reader reliability was calculated as 0.76 [95% CI 0.73-0.80; I2 = 92.13%, Q(50) = 635.08, p < 0.01]. Sources of heterogeneity included magnetic strength, T2WI slice thickness, number of readers, sample size, study design, number of centers, year of publication, proportion of male patients, and mean age. There is substantial reliability in VI-RADS interpretation for MIBC among radiologists with various levels of expertise. The high degree of inter-reader agreement for MIBC detection supports the implementation of VI-RADS in routine clinical practice for the staging paradigm of bladder cancer.

MRI and CT bladder segmentation from classical to deep learning based approaches: Current limitations and lessons.

Precise determination and assessment of bladder cancer (BC) extent of muscle invasion involvement guides proper risk stratification and personalized therapy selection. In this context, segmentation of both bladder walls and cancer are of pivotal importance, as it provides invaluable information to stage the primary tumor. Hence, multiregion segmentation on patients presenting with symptoms of bladder tumors using deep learning heralds a new level of staging accuracy and prediction of the biologic behavior of the tumor. Nevertheless, despite the success of these models in other medical problems, progress in multiregion bladder segmentation, particularly in MRI and CT modalities, is still at a nascent stage, with just a handful of works tackling a multiregion scenario. Furthermore, most existing approaches systematically follow prior literature in other clinical problems, without casting a doubt on the validity of these methods on bladder segmentation, which may present different challenges. Inspired by this, we provide an in-depth look at bladder cancer segmentation using deep learning models. The critical determinants for accurate differentiation of muscle invasive disease, current status of deep learning based bladder segmentation, lessons and limitations of prior work are highlighted.

Pathology grade influences competing mortality risks in elderly men with prostate cancer.

BACKGROUND: Recent guidelines recommend active management of prostate cancer (CaP), especially high-risk disease, in elderly men. However, descriptive data from a large cohort with extended follow up on the risk of death from CaP in men diagnosed over 70 years of age and its relationship to Gleason score (GS) and serum prostate specific antigen (PSA) level is lacking. Using the Surveillance, Epidemiology, and End Results database, we evaluated the influence of GS and serum PSA levels on the risks of mortality from PC (PCM) and mortality from other causes in localized (LPC) and metastatic (MPC) disease in elderly population. METHODS: Men diagnosed with PC over 70 years of age between 2004 and 2016 were divided into LPC and MPC groups, categorized by age: 70-74, 75-79, 80-84, 85-89, and ≥90 years and stratified by GS <7, 7, and >7, and serum PSA level <4, 4-10, 10-20, 20-50, and >50 ng/mL. Competing risk estimates for PCM and mortality from other causes were generated for both groups. RESULTS: Of the 85,649 men, 85.5 % were LPC at diagnosis. Overall, at a median follow up of 4 years, 15% of the men had died including a third from PC. While <15% of men with GS ≤7 died from PC, the PCM was >30% in men with GS >7 in LPC group, which accounted for almost half of total deaths for age 70-84 years. The GS >7 was also significantly associated with PCM in men with MPC. Furthermore, PCM directly correlated with serum PSA levels, with mortality rates reaching up to 50% and 70% for PSA >50 ng/dl for LPC and MPC, respectively. CONCLUSIONS: There is a substantial risk of dying in men diagnosed with LPC over 70 years of age with GS >7 or a serum PSA >20 ng/mL. Furthermore, the risk for death for MPC directly correlated with GS with PCM increasing from 10%-30% for GS ≤7 to >50% for GS >7. The data, in conjunction with other clinical parameters such as comorbidities could be used to counsel elderly men on management options of PC for both localized and metastatic PC.

An Indirect Comparison of Newer Minimally Invasive Treatments for Benign Prostatic Hyperplasia: A Network Meta-Analysis Model.

Objective: This study was designed to provide an indirect comparison of the urinary and sexual domain outcomes and complications after newer minimally invasive surgical therapy (MIST) of Aquablation, Rezum, and UroLift for benign prostatic hyperplasia (BPH) for transurethral resection of prostate (TURP). Methods: We searched Embase, Medline, and Cochrane in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, in December 2019. Only randomized clinical trials (RCTs) that reported outcomes after treatment of BPH for prostate less than 80 g with Aquablation, Rezum, or UroLift were included in the analysis. Results: A total of four RCTs reporting the outcomes after treatment with newer MIST for BPH were identified. Patients undergoing the resective procedures, that is, TURP and Aquablation, had greater improvement in urinary domain outcomes: International Prostate Symptom Score, quality of life, peak flow rate, and postvoiding residual compared to patients undergoing nonresective procedures: UroLift and Rezum. Patients in UroLift group maintained a higher sexual function domain score compared to TURP, but not Aquablation. Our multiple comparison analysis did not reveal a significant difference in urinary and sexual domain scores between patients undergoing UroLift and Rezum at 24 months of follow-up. Conclusions: Aquablation and TURP necessitate general or regional anesthesia and both produced significantly better urinary domain scores compared to Rezum and UroLift. On the other hand, UroLift demonstrated better sexual function domain scores compared to TURP, but not Aquablation. There was no significant difference in urinary domain scores between UroLift and Rezum at 24 months of follow-up.

Intracorporeal versus extracorporeal urinary diversion following robot-assisted radical cystectomy: a meta-analysis, cumulative analysis, and systematic review.

Over the last decade, the increased utilization of robot-assisted radical cystectomy (RARC) in the surgical treatment of muscle-invasive bladder cancer has led to an uptrend in intracorporeal urinary diversions (ICUD). However, the operative results comparing ICUD to extracorporeal urinary diversion (ECUD) have varied widely. We performed a meta-analysis to analyze perioperative outcomes and complications of ICUD compared to ECUD following RARC. This study is registered at International Prospective Register of Systematic Reviews (PROSPERO) CRD42020164074. A systematic literature review was conducted using PubMed, EMBASE, and Cochrane databases in August 2019. A total of six studies comparing ICUD vs ECUD were identified and meta-analysis was conducted on these studies. In addition, a cumulative analysis was also performed on 83 studies that reported perioperative outcomes after RARC and ICUD or ECUD. The Weighed Mean Difference of operative time and blood loss between ICUD and ECUD group was (16; 95% confidence interval - 34 to 66) and (- 86; 95% confidence interval - 124 to - 48), respectively. ICUD and ECUD had comparable early (30-day) and mid-term (30-90-day) complication rate (RR 1.19; 95% confidence interval 0.71-2.0; p = 0.5) and (RR 0.91; 95% confidence interval 0.71-1.15 p = 0.4) respectively. In the 83 studies that were included in the cumulative analysis, the mean operative time for ileal conduit and neobladders by ICUD were 307 and 428 min, respectively, compared to ECUD 428 and 426 min, respectively. ICUD and ECUD have comparable short- and mid-term complication rate. The ICUD group has lower blood loss and lower rate of blood transfusion compared to ECUD.

Combination Therapy for Metastatic Renal Cell Carcinoma: A Systematic Review and Network Meta-analysis.

INTRODUCTION: Randomized clinical trials have shown combination therapy to be superior in progression-free survival (PFS) rates when compared with sunitinib alone. However, there have been no direct comparisons among the combination strategies making it unclear as to which may be the preferred option. We performed a network meta-analysis of the combination therapy (immune checkpoint inhibitor plus axitinib or bevacizumab) used in metastatic renal cell carcinoma (mRCC) and provided a rank order preference based on PFS, and adverse events (AEs). MATERIALS AND METHODS: A systematic search on the treatment of mRCC using combination therapy till July 2019 was done. Studies reporting on combination therapies with immune checkpoint inhibitor plus axitinib or bevacizumab for mRCC were selected. Frequentist method was used for rank order generation. RESULTS: A total of 3 studies consisting of 2672 patients were selected. All combination therapies demonstrated improved PFS when compared with sunitinib alone. The rank order for PFS showed combination of pembrolizumab plus axitinib had the highest probability of favorability followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0.9, 0.7, and 0.4, respectively). For AEs, pembrolizumab plus axitinib had the least AEs ≥grade 3, followed by avelumab plus axitinib and atezolizumab plus bevacizumab (surface under the cumulative ranking 0, 0.5, 1.0). CONCLUSIONS: This network meta-analysis demonstrates that combination of pembrolizumab plus axitinib may be the preferred option based on efficacy and side effect profile compared with avelumab plus axitinib or atezolizumab plus bevacizumab. However, all the 3 combination strategies were superior to sunitinib alone in improving PFS in patients with mRCC.

Comparative efficacy of apalutamide darolutamide and enzalutamide for treatment of non-metastatic castrate-resistant prostate cancer: A systematic review and network meta-analysis.

INTRODUCTION: Studies using apalutamide, enzalutamide, or darolutamide have shown improved metastasis free survival (MFS) rates, leaving clinicians with a dilemma of choosing one over the other, for nonmetastatic castration recurrent prostate cancer (nmCRPC). We performed a network meta-analysis to provide an indirect comparison of oncologic outcomes and adverse events (AEs) of these medications. MATERIAL AND METHODS: We searched PubMed, MEDLINE, and SCOPUS databases, for studies reporting apalutamide, enzalutamide, or darolutamide until January 25, 2020. Results were input into an EndNote library, and data were extracted into a predefined template. Progression free survival (PFS) was defined as radiologic progression or death. Network meta-analysis was done using R and meta-analysis was performed with RevMan v. 5. Surface under the cumulative ranking (SUCRA) value was used to provide rank probabilities. RESULTS: We found 3 studies reporting results for apalutamide, enzalutamide, and darolutamide. MFS was significantly lower in patients receiving darolutamide compared to both apalutamide (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: 0.55-0.97) and enzalutamide (HR: 0.71, 95% CI: 0.54-0.93). MFS was similar for enzalutamide and apalutamide (HR: 0.97, 95% CI: 0.73-1.28). In PFS, apalutamide showed a slightly higher rate compared to darolutamide (HR: 0.76, 95% CI: 0.59-0.99). There was no difference in overall survival (OS) between any of the medications. There was no statistically significant difference in AEs profile of the 3 medications. However, darolutamide had the highest SUCRA value and probability of being the most preferred medication based on AEs profile. CONCLUSION: Enzalutamide and apalutamide had similar and higher MFS rate in indirect comparison with darolutamide. In cases where AEs are concerning, darolutamide might be the preferred agent.