Nachiketh Soodana-Prakash

Robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer (RAZOR): an open-label, randomised, phase 3, non-inferiority trial

BACKGROUND Radical cystectomy is the surgical standard for invasive bladder cancer. Robot-assisted cystectomy has been proposed to provide similar oncological outcomes with lower morbidity. We aimed to compare progression-free survival in patients with bladder cancer treated with open cystectomy and robot-assisted cystectomy. METHODS The RAZOR study is a randomised, open-label, non-inferiority, phase 3 trial done in 15 medical centres in the USA. Eligible participants (aged ≥18 years) had biopsy-proven clinical stage T1-T4, N0-N1, M0 bladder cancer or refractory carcinoma in situ. Individuals who had previously had open abdominal or pelvic surgery, or who had any pre-existing health conditions that would preclude safe initiation or maintenance of pneumoperitoneum were excluded. Patients were centrally assigned (1:1) via a web-based system, with block randomisation by institution, stratified by type of urinary diversion, clinical T stage, and Eastern Cooperative Oncology Group performance status, to receive robot-assisted radical cystectomy or open radical cystectomy with extracorporeal urinary diversion. Treatment allocation was only masked from pathologists. The primary endpoint was 2-year progression-free survival, with non-inferiority established if the lower bound of the one-sided 97·5% CI for the treatment difference (robotic cystectomy minus open cystectomy) was greater than -15 percentage points. The primary analysis was done in the per-protocol population. Safety was assessed in the same population. This trial is registered with ClinicalTrials.gov, number NCT01157676. FINDINGS Between July 1, 2011, and Nov 18, 2014, 350 participants were randomly assigned to treatment. The intended treatment was robotic cystectomy in 176 patients and open cystectomy in 174 patients. 17 (10%) of 176 patients in the robotic cystectomy group did not have surgery and nine (5%) patients had a different surgery to that they were assigned. 21 (12%) of 174 patients in the open cystectomy group did not have surgery and one (1%) patient had robotic cystectomy instead of open cystectomy. Thus, 302 patients (150 in the robotic cystectomy group and 152 in the open cystectomy group) were included in the per-protocol analysis set. 2-year progression-free survival was 72·3% (95% CI 64·3 to 78·8) in the robotic cystectomy group and 71·6% (95% CI 63·6 to 78·2) in the open cystectomy group (difference 0·7%, 95% CI -9·6% to 10·9%; pnon-inferiority=0·001), indicating non-inferiority of robotic cystectomy. Adverse events occurred in 101 (67%) of 150 patients in the robotic cystectomy group and 105 (69%) of 152 patients in the open cystectomy group. The most common adverse events were urinary tract infection (53 [35%] in the robotic cystectomy group vs 39 [26%] in the open cystectomy group) and postoperative ileus (33 [22%] in the robotic cystectomy group vs 31 [20%] in the open cystectomy group). INTERPRETATION In patients with bladder cancer, robotic cystectomy was non-inferior to open cystectomy for 2-year progression-free survival. Increased adoption of robotic surgery in clinical practice should lead to future randomised trials to assess the true value of this surgical approach in patients with other cancer types. FUNDING National Institutes of Health National Cancer Institute.

Lymph node yield as a predictor of overall survival following inguinal lymphadenectomy for penile cancer

OBJECTIVE To determine whether a specific lymph node yield (LNY) affects overall survival (OS) in patients with penile cancer. MATERIALS AND METHODS Using the National Cancer Database, we identified 364 men diagnosed with pSCC who underwent ILND between 2004 and 2013. Men diagnosed on autopsy or at the time of death, patients with preoperative chemotherapy or radiotherapy, M+ and N3 disease, or with less than 3-month of follow-up were excluded. Kaplan-Meier analysis was used to compare Overall Survival (OS). A multivariable Cox regression model was developed to assess predictors of OS. RESULTS The median number of LN retrieved was 16 (IQR: 9-23). There was no significant difference in race, stage, grade for men with LNY ≤15 vs. >15. However, men with LNY ≤15 were significantly older than those with LNY >15 (65 vs. 59 years, p<0.001). On multivariable analysis, radical surgery, age, N+ disease, and LNY ≤15 were independent predictors of worse OS. Patients with LNY ≤15 showed significantly worse 5-year OS versus those with LNY >15 (49% vs. 67%, p=0.008). Nodal density (ND) ≥12.5% was also associated with decreased 5-year OS versus ND <12.5% (31% vs. 70%, p<0.0001). CONCLUSIONS LNY following ILND for pSCC appears to be an independent predictor of OS. A total LNY of >15 following ILND may have a beneficial impact on OS and serve as the threshold for defining an adequate ILND.

Entering an era of radiogenomics in prostate cancer risk stratification

Radiogenomics is a field that amalgamates data from genomics and imaging techniques in order to derive clinically meaningful trends. In this article, we discuss the importance of prostate cancer risk classification and how data derived from genomic testing and multi-parametric magnetic resonance imaging (mpMRI) can be integrated into clinical decision-making processes with a focus on active surveillance (AS). Finally, we describe an ongoing prospective trial (Miami MAST trial) which incorporates imaging (mpMRI) and radiomics data in patients who are on AS for prostate cancer.

Elevated Body Mass Index Is Associated with Secondary Hypogonadism Among Men Presenting to a Tertiary Academic Medical Center

Purpose To characterize the population of hypogonadal men who presented to a tertiary academic urology clinic and evaluate risk factors for primary vs. secondary hypogonadism. Materials and Methods We evaluated all men with International Classification of Diseases-9 diagnosis codes R68.82 and 799.81 for low libido, 257.2 for testicular hypofunction, and E29.1 for other testicular hypofunction at a tertiary academic medical center from 2013 to 2017. We included men who had testosterone (T) and luteinizing hormone (LH) drawn on the same day. We classified men based on T and LH levels into eugonadal, primary, secondary, and compensated hypogonadism. Risk factors including age, body mass index (BMI) over 30 kg/m2, current smoking status, alcohol use greater than 5 days per week, and Charlson comorbidity index greater than or equal to 1 were investigated and measured in each group using the eugonadal group for reference. Results Among the 231 men who had both T and LH levels, 7.4%, 42.4%, and 7.4% were classified as primary, secondary, and compensated hypogonadism, respectively. Only elevated BMI was associated with secondary hypogonadism compared to eugonadal men (median BMI, 30.93 kg/m2 vs. 27.69 kg/m2, p=0.003). BMI, age, comorbidities, smoking, or alcohol use did not appear to predict diagnosis of secondary hypogonadism. Conclusions Secondary hypogonadism appears to be the most common cause of hypogonadism among men complaining of low T and decreased libido at a tertiary academic medical center. Secondary hypogonadism is associated with elevated BMI and therefore obesity should be used as a marker to evaluate men for both T and LH levels.

Optimizing patient's selection for prostate biopsy: A single institution experience with multi-parametric MRI and the 4Kscore test for the detection of aggressive prostate cancer

Objectives To evaluate the performance of mpMRI and the 4Kscore test together for the detection of significant prostate cancer. Material and methods We selected a consecutive series of men who were referred for evaluation of prostate cancer at an academic institution and underwent mpMRI and the 4Kscore test. The primary outcome was the presence of Gleason 7 or higher cancer on biopsy of the prostate. We used logistic regression and Decision Curve Analysis to report the discrimination and clinical utility of using mpMRI and the 4Kscore test for prostate cancer detection. We modeled the probability of harboring a Gleason 7 or higher prostate cancer based on the 4Kscore test and mpMRI findings. Finally, we examined various combinations and sequences of mpMRI and the 4Kscore test and assessed the impact on biopsies avoided and cancers missed. Results Among 300 men who underwent a 4Kscore test and mpMRI, 149 (49%) underwent a biopsy. Among those, 73 (49%) had cancer, and 49 (33%) had Gleason 7 cancer. The area under the curve (AUC) for using the 4Kscore test and mpMRI together 0.82 (0.75–0.89) was superior to using the 4Kscore 0.70 (0.62–0.79) or mpMRI 0.74 (0.66–0.81) individually (p = 0.001). Similarly, decision analysis revealed the highest net benefit was achieved using both tests. Conclusions The 4Kscore test and mpMRI results provide independent, but complementary, information that enhances the prediction of higher-grade prostate cancer and improves patient’s selection for a prostate biopsy. Prospective trials are required to confirm these findings.

Racial disparity and survival outcomes between African-American and Caucasian American men with penile cancer

To determine whether there is a survival difference for African‐American men (AAM) versus Caucasian American men (CM) with penile squamous cell carcinoma (pSCC), particularly in locally advanced and metastatic cases where disease mortality is highest.

Defining the optimal PSA range for the maximal predictive efficacy of PSA density to detect prostate cancer on biopsy: Results from a multi-institutional and prospective contemporary cohort.

70 Background: PSA density (PSAD) is an important predictor of prostate cancer (PCa). We assessed whether the predictive accuracy of PSAD varied based on the range of PSA or whether the patient had a previous negative prostate biopsy (PB). Methods: We assessed a prospective cohort of men who were referred for a PB due to suspicion of PCa at 26 different sites across USA. The area under the receiver operating characteristic curve (AUC) was used to assess the added predictive accuracy of PSAD versus PSA across 3 different PSA ranges ( 10 ng/mL) and in men with or without a prior negative PB for the detection of any and significant (Gleason ≥ 7) PCa. Results: Of the 1,290 men, 585 (45%) and 284 (22%) had any and significant PCa, respectively. PSAD was significantly more predictive than PSA for detecting any PCa in the PSA ranges of 4 – 10 (AUC 0.70 vs 0.53, P 10 (AUC 0.84 vs 0.65, P < 0.00001) ng/mL. Similarly, for significant PCa, PSAD was more predictive than PSA in the PSA ...

Role of non-neoplastic renal parenchyma abnormalities in the population with preoperative CKD.

586 Background: Renal cancer is associated with chronic kidney disease. Several studies have shown a 20% rate of preoperative CKD in the population undergoing partial nephrectomy. The non-neoplastic abnormalities (NNA) surrounding a tumor have been suggested as surrogates for long term renal failure. We have endeavored to describe the most relevant features within the above mentioned kidney area in patients with and without preoperative CKD. Methods: We retrospectively reviewed 201 patients who underwent nephrectomy between 2012 and 2014 with available histological assessment of NNA. Additional factors were included in the analysis such as demographic characteristics (age, sex, BMI) and comorbidities (hypertension, diabetes, Charlson comorbidity index). Pathological features were grouped as follows: glomerular (GA), interstitial (IA) or vascular abnormalities (VA). Univariate and multivariate logistic regression analyses were used to determine the associations between NNA and the presence of preoperative ...

Cancer detection between peripheral zone and transitional zone targeted biopsies: Preliminary results from a prospective cohort of men undergoing MRI-US fusion biopsy.

56 Background: Multiparametric MRI has emerged as a popular imaging modality to localize prostate cancer. Nevertheless, interpretation of MRI is subjective, with concerns for false positives, particularly in the transitional zone (TZ), where hyperplastic changes may be confused for suspicion of cancer. We analyzed a prospective cohort of men undergoing MRI-US fusion biopsy and compared cancer detection rate between lesions seen in the peripheral zone (PZ) and the TZ. Methods: 133 men with elevated PSA or positive DRE underwent MRI-US fusion biopsy with average of 2 cores taken per target for the detection of prostate cancer between October 2014 and July 2015. Each targeted lesion in the PZ and TZ was previously classified by radiologists according to the MRI PI-RADS score and grouped according to their level of suspicion as probably benign (1-2), indeterminate (3) or probably malignant (4-5). Histopathology from targeted cores were categorized as no cancer, non-significant cancer (Gleason 6) and significa...

Comparison of survival outcomes for African American and Caucasian men with advanced penile cancer in Florida.

490 Background: Studies suggest that there may be disparity in clinical outcomes for African−American men (AAM) compared to Caucasian men (CM) with penile squamous cell carcinoma (SCC). We sought to determine whether there was a survival difference for African American versus Caucasian men, particularly in locally advanced and metastatic cases of penile SCC where disease mortality is highest. Methods: Using the Florida Cancer Data System, we identified men diagnosed with penile SCC, from 2004 to 2014. We excluded men who were diagnosed on autopsy or at the time of death and with < 6 months of follow up. Demographic variables including: age, follow−up, stage, race and treatment type were compared between AAM and CM. Treatment type was categorized as surgery alone or surgery plus additional therapy (chemotherapy and/or radiation). For locally advanced and metastatic disease, we compared treatment type and overall survival (OS) between AAM and CM. A multivariable model was developed to determine significant ...