Radical prostatectomy cancer grade and percentage of Gleason pattern 4 estimated by global vs individual tumor grading correlate differently with the risk of biochemical recurrence in Grade Group 2 and 3 cancers.

OBJECTIVES: There are 2 grading approaches to radical prostatectomy (RP) in multifocal cancer: Grade Group (GG) and percentage of Gleason pattern 4 (GP4%). We investigated whether RP GG and GP4% generated by global vs individual tumor grading correlate differently with biochemical recurrence. METHODS: We reviewed 531 RP specimens with GG2 or GG3 cancer. Each tumor was scored separately with assessment of tumor volume and GP4%. Global grade and GP4% were assigned by combining Gleason pattern 3 and 4 volumes for all tumors. Correlation of GG and GP4% generated by 2 methods with biochemical recurrence was assessed by Cox proportional hazard regression and receiver operating characteristic curves, with optimism adjustment using a bootstrap analysis. RESULTS: Median age was 63 (range, 42-79) years. Median prostate-specific antigen was 6.3 (range, 0.3-62.9) ng/mL. In total, the highest-grade tumor in 371 (36.9%) men was GG2 and in 160 (30.1%) men was GG3. Global grading was downgraded from GG3 to GG2 in 37 of 121 (30.6%) specimens with multifocal disease, and 145 of 404 (35.9%) specimens had GP4% decreased by at least 10%. Ninety-eight men experienced biochemical recurrence within a median of 13 (range, 3-119) months. Men without biochemical recurrence were followed up for a median of 47 (range, 12-205) months. Grade Group, GP4%, and margin status correlated with the risk of biochemical recurrence using highest-grade tumor and global grading, but the degrees of these correlations varied and were statistically significantly different between the 2 grading approaches. CONCLUSIONS: Grade Group, GP4%, and margin status derived by global vs individual tumor grading predict postoperative biochemical recurrence statistically significantly differently. This difference has important implications if results derived from cohorts graded using different methods are compared.

Optimum threshold of the 4Kscore for biopsy in men with negative or indeterminate multiparametric magnetic resonance imaging.

Objective: The study aims to identify the optimal 4Kscore thresholds to determine the need for a prostate biopsy when multiparametric magnetic resonance imaging (MRI) (mpMRI) is negative or indeterminate. Materials and methods: We analysed retrospective data from men in eight different institutions who underwent an mpMRI, 4Kscore and prostate biopsy for evaluation of prostate cancer. We selected men with a negative (PIRADS ≤2) or indeterminate (PIRADS 3) mpMRI. 4Kscore values were categorized into ranges of 1-7, 8-19, 20-32 and greater than 32. We evaluated the proportion of men with grade group 2 or higher (GG2+) cancer in groups defined by PIRADS and 4Kscore. We also evaluated the number of biopsies avoided and GG2+ cancer missed in each group reported depend on 4Kscore cutoff points. Results: Among 1111 men who had an mpMRI, 4Kscore and biopsy, 625 of them had PIRADS ≤3 on mpMRI: 374 negative (PIRADS ≤2) and 251 indeterminate (PIRADS 3). In men with a negative mpMRI, we found a 4Kscore cut-point of 33 resulted in an increased risk of GG2+ cancer on biopsy. In patients with an equivocal lesion on mpMRI, men with a 4Kscore cutoff ≥8 had a greater risk of GG2+ cancer on biopsy. Decision curve analysis supported the proposed cut-points in each mpMRI group. Conclusions: In men with negative and indeterminate mpMRI, we found the best 4Kscore threshold to determine the need for biopsy to be 33 and 8 respectively. Future prospective studies in independent populations are needed to confirm these findings.

Pushing Fluids: A Case for Liquid Biomarkers Before Imaging in Pre-Prostate Biopsy Decision-making.

For patients with clinical suspicion of prostate cancer, liquid biomarkers are the next best test because of their accessibility, objectiveness, and noninvasive nature. A highly sensitive cutoff for these biomarkers should be used to triage patients before use of magnetic resonance imaging.

Overcoming Drug Resistance in Advanced Prostate Cancer by Drug Repurposing.

Prostate cancer (PCa) is the second most common cancer in men. Common treatments include active surveillance, surgery, or radiation. Androgen deprivation therapy and chemotherapy are usually reserved for advanced disease or biochemical recurrence, such as castration-resistant prostate cancer (CRPC), but they are not considered curative because PCa cells eventually develop drug resistance. The latter is achieved through various cellular mechanisms that ultimately circumvent the pharmaceutical's mode of action. The need for novel therapeutic approaches is necessary under these circumstances. An alternative way to treat PCa is by repurposing of existing drugs that were initially intended for other conditions. By extrapolating the effects of previously approved drugs to the intracellular processes of PCa, treatment options will expand. In addition, drug repurposing is cost-effective and efficient because it utilizes drugs that have already demonstrated safety and efficacy. This review catalogues the drugs that can be repurposed for PCa in preclinical studies as well as clinical trials.

Prostatic Ductal Adenocarcinoma Controlled for Tumor Grade, Stage, and Margin Status Does Not Independently Influence the Likelihood of Biochemical Recurrence in Localized Prostate Cancer After Radical Prostatectomy.

CONTEXT.­: Prostatic ductal adenocarcinoma (PDA) has historically been considered to be an aggressive subtype of prostate cancer. OBJECTIVE.­: To investigate if PDA is independently associated with worse biochemical recurrence (BCR)-free survival after radical prostatectomy. DESIGN.­: A review of 1584 radical prostatectomies was performed to grade, stage, and assess margin status in each tumor nodule. Radical prostatectomies with localized PDA (ie, those lacking metastasis) in the tumor nodule with the highest grade and stage and worst margin status were matched with prostatic acinar adenocarcinoma according to grade, stage, and margin status. The effect of PDA on BCR was assessed by multivariable Cox regression and Kaplan-Meier analyses. RESULTS.­: Prostatic ductal adenocarcinoma was present in 171 cases. We excluded 24 cases because of lymph node metastasis (n = 13), PDA not in the highest-grade tumor nodule (n = 9), and positive surgical margin in a lower-grade tumor nodule (n = 2). The remaining 147 cases included 26 Grade Group (GG) 2, 44 GG3, 6 GG4, and 71 GG5 cancers. Seventy-six cases had extraprostatic extension, 33 had seminal vesicle invasion, and 65 had positive margins. Follow-up was available for 113 PDA and 109 prostatic acinar adenocarcinoma cases. Prostate-specific antigen density (odds ratio, 3.7; P = .001), cancer grade (odds ratio, 3.3-4.3; P = .02), positive surgical margin (odds ratio, 1.7; P = .02), and tumor volume (odds ratio, 1.3; P = .02) were associated with BCR in multivariable analysis. Prostatic ductal adenocarcinoma, its percentage, intraductal carcinoma, and cribriform Gleason pattern 4 were not significant independent predictors of BCR. CONCLUSIONS.­: Advanced locoregional stage, higher tumor grade, and positive surgical margin status rather than the mere presence of PDA are more predictive of worse BCR-free survival outcomes following radical prostatectomy in men with a component of PDA.

The role of pre-biopsy mpMRI in lymph node staging for prostate cancer.

INTRODUCTION: Prostate cancer (PCa) staging is an integral part in the management of prostate cancer. The gold standard for diagnosing lymph node invasion is a surgical lymphadenectomy, with no superior imaging modality available at the clinician's disposal. Our aim in this study is to identify if a pre-biopsy multiparametric MRI (mpMRI) can provide enough information about pelvic lymph nodes in intermediate and high risk PCa patients, and whether it can substitute further cross sectional imaging (CSI) modalities of the abdomen and pelvis in these risk categories. METHODS: Patients with intermediate and high risk prostate cancer were collected between January 2015 and June 2019, while excluding patients who did not undergo a pre-biopsy mpMRI or a CSI. Date regarding biopsy result, PSA, MRI results, CSI imaging results were collected. Using Statistical Package for the Social Sciences (SPSS) version 24.0, statistical analysis was conducted using the Cohen's Kappa agreement for comparison of mpMRI with CSI. McNemar's test and receiver operator curve (ROC) curve were used for comparison of sensitivity of both tests when comparing to the gold standard of lymphadenectomy. RESULTS: A total of 143 patients fit the inclusion criteria. We further stratified our patients into according to PSA level and Gleason score. Overall, agreement between mpMRI and all CSI was 0.857. When stratifying patients based on Gleason score and PSA, the higher the grade or PSA, the higher agreement between mpMRI and CSI. The sensitivity of mpMRI (73.7%) is similar to CSI (68.4%). When comparing CSI sensitivity to that of mpMRI, no significant difference was present by utilizing the McNemar test and very similar receiver operating characteristic curve. CONCLUSION: A pre-biopsy mpMRI can potentially substitute further cross sectional imaging in our cohort of patients. However, larger prospective studies are needed to confirm our findings.

Outcomes of active surveillance for clinically localized prostate cancer in a middle eastern tertiary care center.

BACKGROUND: The aim of our study was to evaluate the outcome of active surveillance (AS) for prostate cancer for a cohort of patients at our institution. METHODS: A total of 43 patients with low risk prostate cancer were enrolled in an active surveillance pilot program at our institution between 2008 and 2018. Follow up protocols included: periodic prostate specific antigen (PSA), digital rectal examination (DRE), multiparametric MRI, and prostate biopsy at one year. Pertinent parameters were collected, and descriptive statistics were reported along with a subset analysis of patients that dropped out of the protocol to receive active treatment for disease progression. RESULTS: Out of 43 eligible patients, 46.5% had a significant rise in follow up PSA. DRE was initially suspicious in 27.9% of patients, and none had any change in DRE on follow up. Initially, prostate MRIs showed PIRADS 3, 4, and 5 in 14%, 37.2%, and 11.6% respectively, while 23.2% had a negative initial MRI. 14% did not have an MRI. Upon follow up, 18.6% of patients had progression on MRI. Initial biopsies revealed that 86% were classified as WHO group 1, while 14% as WHO group 2. With regards to the follow up biopsies, 11.6% were upgraded. 20.9% of our patients had active treatment; 44.4% due to upgraded biopsy results, 22.2% due to PSA progression, 22.2% due to strong patient preference, and 11.1% due to radiologic progression. CONCLUSIONS: For selected men with low risk prostate cancer, AS is a reasonable alternative. The decision for active treatment should be tailored upon changes in PSA, DRE, MRI, and biopsy results.

Comparative analysis of histopathological subtypes of renal cell carcinoma in the Middle East compared to other world regions.

INTRODUCTION: Renal cell carcinoma (RCC) has various histopathological tumor subtypes which have a significant implication on the oncological outcome of these patients. We aimed to evaluate the distribution of RCC subtypes presenting at a tertiary care center in the Middle East, in comparison to the distribution reported in different geographic areas worldwide. METHODS: A retrospective chart review was conducted on all patients who underwent partial or radical nephrectomy for RCC at the American University of Beirut Medical Center between January 2012 and January 2018. Data on histologic subtypes were compiled and compared to representative series from different continents. RESULTS: One hundred and seventy-nine patients with RCC were identified, of whom 122 (68.2%) were classified as clear cell, 30 (16.8%) as papillary, 17 (9.5%) as chromophobe, and 10 (5.6%) as unclassified. When compared to other regions of the world, this Middle Eastern series demonstrated a higher prevalence of the chromophobe subtype compared to Western populations (9.5% in the Middle East vs. 5.3% in the US and 3.1% in Europe) and a lower prevalence of clear cell subtype (68.2% in the Middle East vs. 78.7% in the US and 85.8% in Europe). Conversely, there was a higher prevalence of papillary RCC in the Middle East (16.8%) compared to North America (13.1%, 95% confidence interval [CI]: 12.7-13.6), Europe (11.1%, 95% CI: 10.0-12.1), and Australia (10.2%). The prevalence of chromophobe and clear cell RCC in the Middle East was similar to that reported in South America. CONCLUSIONS: The distribution of RCC subtypes in this Middle Eastern cohort was significantly different from that reported in the Western hemisphere (Europe and the US) but similar to that reported in South America and Australia. These findings may point to a possible genetic predisposition underlying the global variation in distribution.

Is age an independent risk factor for perioperative mortality and morbidity after radical prostatectomy? Analysis of the American college of surgeons national surgical quality improvement program database.

OBJECTIVES: To assess the safety and surgical outcomes of radical prostatectomy (RP) when looking at age as an independent risk factor of perioperative mortality and morbidity. PATIENTS AND METHODS: A retrospective cohort study was performed using American College of Surgeons National Surgical Quality Improvement Program database. Patients who underwent a RP from 2008 to 2015 were identified. They were divided into three groups based on their age 15 group at the time of surgery. Patients' characteristics were compared across the three following age groups: 74 years. The correlation between the three different age groups and their respective 30-day postoperative mortality and morbidity were assessed using logistic regression. Unadjusted and adjusted odds ratios (ORs) were estimated. RESULTS: A total of 43025 patients were identified, 81.7% were aged 74 years. Overall, 102 patients died in the 30-day postoperative period. Univariate and multivariate analysis showed a significant increase in the 30-day postoperative mortality from 0.1% to 0.4% to 1.3% in the three different age groups 74 years, respectively. In addition, there was a significant increase in postoperative complications in the group of patients aged >74 years. A higher risk of complications 25 related to cardiac (OR 2.18 in age group 70-74 vs OR 7.45 in age group >74 years), respiratory (OR 2.36 vs OR 5.91), neurological (OR 2.28 vs OR 3.44), wound infections (OR 1.49 vs OR 3.25), and sepsis (OR 1.54 vs OR 2.64) were seen with the youngest group taken as a reference. CONCLUSION: Age is an independent risk factor for perioperative mortality and morbidity after RP in elderly patients. Therefore, age should be considered in the decision making of therapeutic options for patients with prostate cancer. ABBREVIATIONS: BMI: body mass index; CNS: central nervous system; SIOG: International Society of Geriatric Oncology; SEER: Surveillance, Epidemiology, and End Results; ACS: American College of Surgeons; NSQIP: National Surgical Quality Improvement Program; OR: odds ratio.

An evaluation of the timing of surgical complications following radical prostatectomy: Data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).

OBJECTIVE: To perform a time-to-complication analysis for radical prostatectomy (RP) and computing risk factors for these complications, as RP is established as a first-line treatment for localised prostate cancer with excellent oncological outcomes but is not without its complications. PATIENTS AND METHODS: We used the National Surgical Quality Improvement Program (NSQIP) database to analyse data of patients who underwent RP, between 2008 and 2015, with the primary endpoint of time-to-complications. Categorical variables were analysed using descriptive statistics and continuous variables were recorded as medians and interquartile ranges (IQRs) such as timing of complications. Multivariable regression analyses were used to analyse time-to-complication and its effect on other outcomes. A P < 0.05 was defined as statistically significant. RESULTS: The overall 30-day complication rate was 7.54% and was equally distributed before and after discharge. Bleeding/transfusion (3.37%), urinary tract infection (1.58%), deep venous thrombosis (DVT; 0.74%), and wound infection (1.08%) were the five most common complications after RP. The median (IQR) time-to-complication unique for each complication was: bleeding/transfusion occurred on the same operative day (1), renal complications occurred at 4 (2-6) days, sepsis at 12 (6.5-17.5) days, DVT at 11 (5.5-16.5) days, pneumonia at 4 (0.5-7.5) days, and cardiac arrest occurred at 5 (1.75-8.25) days. After discharge complications were associated with greater odds of re-admission (odds ratio [OR] 16.40, P < 0.001), but associated with a lesser length of stay (OR - 3.33, P < 0.001) when compared to pre-discharge complications. CONCLUSION: Several risk factors predict pre- and post-discharge complication rates. Knowledge regarding the timing of complications and their respective risk factors should improve patient-physician communication and prediction, and thus patient care. ABBREVIATIONS: ACS: American College of Surgeons; BMI: body mass index; DM: diabetes mellitus; DVT: deep venous thrombosis; Hct: haematocrit; IQR: interquartile range; LOS: length of stay; NSQIP: National Surgical Quality Improvement Program; OR: odds ratio; RP: radical prostatectomy.

Development of a novel nomogram incorporating platelet-to-lymphocyte ratio for the prediction of lymph node involvement in prostate carcinoma.

OBJECTIVE: The available nomograms used to predict lymph node involvement (LNI) are not comprehensive. We sought to derive a novel nomogram incorporating the platelet to lymphocyte ratio (PLR) to predict LNI and compare its performance to validated preoperative risk nomograms in a cohort of men undergoing robotic-assisted radical prostatectomy at our institution. METHODS: Our electronic health record was queried for patients who underwent robotic-assisted radical prostatectomy with bilateral pelvic lymphadenectomy between 2013 and 2019. A bootstrapped multivariate logistic regression model was constructed for the predictors of LNI while adjusting for other covariates. Then, we used the derived logistic regression formula to estimate each patient's risk (%) for LNI. Individualized risks were also calculated using the following verified nomograms: Briganti-2012, Cagiannos, Godoy, and Memorial Sloan Kettering Cancer Center. Subsequently, we plotted the risks for our nomogram and the 4 verified nomograms into receiver operating characteristics curves. We reported the area under the curve (AUC) for each of the 5 nomograms and the corresponding 95% confidence interval (CI). RESULTS: The cohort included 173 patients, of which 13.9% demonstrated LNI. LNI was associated with higher preoperative prostate-specific antigen (PSA) ≥ 10 [odds ratio [OR] = 4.89; 95% confidence interval [CI] (1.42-16.83)], higher grade (WHO group ≥ 3)[19.21; (2.23-195.25)], and higher percentage of positive biopsy cores (≥60%) [3.38, (1.04-11.00)]. With every 30-unit increase in PLR the risk of LNI increased by 47%. The nomogram derived from our data had the highest AUC [(AUC 0.877; 95% CI (0.806-0.947)]. The Memorial Sloan Kettering Cancer Center and Briganti 2012 displayed almost congruent ability [0.836; 95% CI (0.758-0.915)] and [0.827; (0.752-0.902)] to identify patients with positive nodes in our cohort with perfect sensitivity and negative predictive value. CONCLUSION: The nomogram incorporating PLR demonstrated 94.7% sensitivity to predict LNI and avoided pelvic lymphadenectomy in half of the patients at a cut-off between 6.5% and 8.5%. A prospective study with a larger sample is needed to validate our findings.

Practice patterns in ordering a voiding cystourethrogram for pediatric patients among different specialties in a Middle Eastern tertiary care center.

INTRODUCTION: Voiding cystourethrogram (VCUG) is a very popular test performed to evaluate genitourinary tract anomalies. Nevertheless, this test can be overused and can lead to unnecessary patient discomfort, radiation exposure, and cost. We sought to study the practice patterns in ordering a VCUG in a Middle Eastern tertiary care center. METHODS: Over a period of 3 years, a retrospective analysis of all VCUG images done for pediatric patients in a single center was made. Further clinical details were extracted from the electronic health records. The specialty of an ordering physician and the reported indication for the procedure were noted. Indications for VCUG were recorded based on the AAP 2011 guidelines, NICE guidelines 2007, and ACR 2011 guidelines. Based on these criteria, patients were analyzed. RESULTS: A total of 92 VCUGs were evaluated. Of all VCUGs done, pediatricians ordered the most VCUGs (50/92), followed by pediatric infectious disease (16/92), pediatric nephrology (9/92), pediatric urology (7/92), adult urology (5/92), pediatric surgery (3/92), obstetrician-gynecologist (1/92), and emergency medicine (1/92). Properly indicated VCUGs were 50% by general pediatrics, 55% by pediatric infectious disease, 45% by pediatric nephrology, 40% by adult urology, 33% by pediatric surgery, and 100% by pediatric urology. CONCLUSION: VCUG is utilized differently by different specialties. In some centers, adult specialties may order a pediatric VCUG. General pediatricians order VCUG the most with a tendency for misuse in up to 50%. Pediatric urology is not the most ordering specialty of VCUG; however, it utilizes it most appropriately. The noted practice patterns may be improved with awareness of the indications and limitations of the study and with proper referral.