Vivek Venkatramani

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.

Re-examining Prostate-specific Antigen (PSA) Density: Defining the Optimal PSA Range and Patients for Using PSA Density to Predict Prostate Cancer Using Extended Template Biopsy

OBJECTIVE To compare the predictive accuracy of prostate-specific antigen (PSA) density vs PSA across different PSA ranges and by prior biopsy status in a prospective cohort undergoing prostate biopsy. MATERIALS AND METHODS Men from a prospective trial underwent an extended template biopsy to evaluate for prostate cancer at 26 sites throughout the United States. The area under the receiver operating curve assessed the predictive accuracy of PSA density vs PSA across 3 PSA ranges (<4 ng/mL, 4-10 ng/mL, >10 ng/mL). We also investigated the effect of varying the PSA density cutoffs on the detection of cancer and assessed the performance of PSA density vs PSA in men with or without a prior negative biopsy. RESULTS Among 1290 patients, 585 (45%) and 284 (22%) men had prostate cancer and significant prostate cancer, respectively. PSA density performed better than PSA in detecting any prostate cancer within a PSA of 4-10 ng/mL (area under the receiver operating characteristic curve [AUC]: 0.70 vs 0.53, P < .0001) and within a PSA >10 mg/mL (AUC: 0.84 vs 0.65, P < .0001). PSA density was significantly more predictive than PSA in detecting any prostate cancer in men without (AUC: 0.73 vs 0.67, P < .0001) and with (AUC: 0.69 vs 0.55, P < .0001) a previous biopsy; however, the incremental difference in AUC was higher among men with a previous negative biopsy. Similar inferences were seen for significant cancer across all analyses. CONCLUSION As PSA increases, PSA density becomes a better marker for predicting prostate cancer compared with PSA alone. Additionally, PSA density performed better than PSA in men with a prior negative biopsy.

Propensity matched comparative analysis of survival following chemoradiation or radical cystectomy for muscle-invasive bladder cancer

To compare survival outcome between chemoradiation therapy (CRT) and radical cystectomy (RC) for muscle‐invasive bladder cancer (MIBC).

Reclassification Rates of Patients Eligible for Active Surveillance After the Addition of Magnetic Resonance Imaging-Ultrasound Fusion Biopsy: An Analysis of 7 Widely Used Eligibility Criteria

OBJECTIVES To evaluate the impact of adding magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy cores to standard 12-core biopsy in selecting men for active surveillance (AS). MATERIALS AND METHODS Among men undergoing a fusion biopsy for evaluation of prostate cancer, we selected men who were eligible for at least 1 of 7 different AS criteria based on the standard biopsy alone. We assessed each patients eligibility for each AS criterion with and without the inclusion of fusion biopsy cores. The primary end point was the proportion of men who were initially eligible for AS but became ineligible after addition of the fusion biopsy cores. RESULTS A total of 100 men were eligible for at least 1 AS criterion. After addition of fusion biopsy cores, the proportion of men who became ineligible for AS varied from 10.3% to 40.7%. Criteria that incorporated an absolute maximum number of cores positive had the highest rates of ineligibility. Using a percentage of cores positive helped to reduce the number of patients who would have been excluded. Combining the targeted biopsy cores into one, or taking the single core with the highest grade or volume did not appear to reduce the proportion of men who became ineligible. CONCLUSIONS The addition of fusion biopsy to standard 12-core biopsy significantly increased the number of men who became ineligible for AS. Using the percent of cores positive, instead of an absolute number, allowed fewer exclusions. AS criteria may need to be updated to prevent the unnecessary exclusion of men due to an oversampling of low-risk disease.

Using microscope for onco-testicular sperm extraction for bilateral testis tumors

OBJECTIVE To demonstrate a step-by-step approach to the use of the operating microscope for onco-testicular sperm extraction. DESIGN Video presentation. SETTING University hospital. PATIENT(S) A 34-year-old man (status post right orchiectomy at another institution for pT3 pure seminoma with negative preoperative tumor markers) was referred for contralateral orchiectomy for multifocal left testis mass and fertility preservation. A postoperative semen analysis for attempted cryopreservation of ejaculated semen identified azoospermia. INTERVENTION(S) Left radical orchiectomy, left microsurgical onco-testicular sperm extraction (TESE). MAIN OUTCOME MEASURE(S) Intraoperative technique with commentary highlighting tips for successful fertility preservation via microsurgical onco-TESE. Discussion of alternatives. RESULT(S) This video provides a step-by-step guide to microsurgical onco-TESE coordinated with radical orchiectomy for testis cancer as a means of fertility preservation in an azoospermic patient. Preoperative imaging with scrotal ultrasound can serve as a useful guide for targeting microdissection to areas of normal testicular parenchyma for extraction of seminiferous tubules likely to host normal spermatogenesis. This patient had successful recovery and cryopreservation of abundant testicular sperm following targeted ex-vivo testicular microdissection. CONCLUSION(S) Microsurgical onco-TESE may be offered to azoospermic patients when undergoing orchiectomy for testis cancer. Use of preoperative imaging and the surgical microscope guide surgical dissection and optimize sperm recovery.

Trends in Utilization of Robotic and Open Partial Nephrectomy for Management of cT1 Renal Masses

BACKGROUND Partial nephrectomy is widely used for surgical management of small renal masses. Use of robotic (RPN) versus open partial nephrectomy (OPN) among various populations is not well characterized. OBJECTIVE To analyze trends in utilization of RPN and disparities that may be associated with this procedure for management of cT1 renal masses in the USA. DESIGN, SETTING, AND PARTICIPANTS Patients who underwent RPN or OPN for clinical stage T1N0M0 renal masses in the USA from 2010 to 2013 were identified in the National Cancer Data Base. A total of 23 154 patients fulfilled the inclusion criteria. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Univariable and multivariable logistic regression analyses were performed to evaluate differences in receiving RPN or OPN across various patient groups. RESULTS AND LIMITATIONS Utilization of RPN increased from 41% in 2010 to 63% in 2013. Black patients (adjusted odds ratio [aOR] 0.91, 95% confidence interval [CI] 0.84-0.98) and Hispanic patients (aOR 0.85, 95% CI 0.77-0.95) were less likely to undergo RPN. RPN was less likely to be performed in rural counties (aOR 0.80, 95% CI 0.66-0.98) and in patients with no insurance (aOR 0.52, 95% CI 0.44-0.61) or patients covered by Medicaid (aOR 0.81, 95% CI 0.73-0.90). There was no significant difference in RPN utilization between academic and non-academic facilities. Patients with higher clinical stage (aOR 0.58, 95% CI 0.55-0.62) and comorbidities (aOR 0.79, 95% CI 0.71-0.88) were also less likely to undergo RPN. CONCLUSIONS Utilization of RPN has continued to increase over time; however, there are significant disparities in its utilization according to race and socioeconomic status. Black and Hispanic patients and patients in rural communities and with limited insurance were more likely to be treated with OPN instead of RPN. PATIENT SUMMARY The use of robotic surgery in partial nephrectomy for management of small renal masses has increased over time. We found a significant disparity across different racial and socioeconomic groups in use of robotic partial nephrectomy compared to open surgery. Patients living in rural areas, with limited insurance, and multiple medical comorbidities were more likely to undergo open than robotic partial nephrectomy.

Disparities in Hispanic/Latino and non-Hispanic Black men with low-risk prostate cancer and eligible for active surveillance: a population-based study

BackgroundNon-Hispanic Black (NHB) men are at an increased risk for aggressive prostate cancer (PCa), making active surveillance (AS) potentially less optimal in this population. This concern has not been explored in other minority populations—specifically, Hispanic/Latino men. We recently found that Mexican-American men demonstrate an increased risk of PCa-specific mortality, and we hypothesized that they may also be at risk for an adverse outcome on AS.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) program, we extracted a population-based cohort of men diagnosed from 2004 to 2013 with localized or regional PCa, who had ≤2 cores of only Grade Group (GG) 1 cancer, and underwent radical prostatectomy (RP) with available biopsy and surgical pathology results. We measured discovery of high-risk PCa at RP and collected socioeconomic status (SES) data across different racial/ethnic groups. We defined aggressive tumors as either an upgrade to GG 3 or higher (GG3+) cancer or non-organ-confined disease (≥pT3a or N1). Univariate and multivariate logistic regression models were developed to assess the association between racial/ethnic categories and the previously mentioned adverse oncologic outcomes both with and without adjusting for SES factors.ResultsNHB and Mexican-American men were significantly more likely to have aggressive PCa, following RP. In multivariable logistic regression adjusting for SES factors and relative to non-Hispanic White (NHW) men, Mexican-American men had at increased odds of upgrading to GG3+ (OR 1.67; 95% CI [1.00–2.90]). NHB men were more likely to have non-organ-confined disease (OR 1.34; 95% CI [1.06–1.69]), while Mexican-American men had a similar risk to NHW men.ConclusionAmong individuals with low-risk PCa and eligible for AS, Mexican-American and NHB men are at an increased risk of harboring more aggressive disease at RP. This novel finding among Mexican-Americans deserves further evaluation.

High-Intensity Focused Ultrasound (HIFU) Options for High-Risk Prostate Cancer

Radical treatment of the entire prostate gland is still the standard of care for high-risk PCa. However, focal HIFU ablation is a safe procedure and has shown promising short-term oncological outcomes, with acceptable complication rate and excellent functional outcomes. Prospective studies with long-term follow-up are needed to determine the true role of focal HIFU for PCa. Until then, focal HIFU should be offered only in the setting of clinical trials, particularly for high-risk PCa.

Robot-Assisted Radical Cystectomy Versus Open Radical Cystectomy

Radical cystectomy is suited to a minimally invasive approach, and robotic surgery holds the potential for improving perioperative morbidity compared with open surgery, without a compromise of oncological efficacy. Recent meta-analyses have shown that minimally invasive cystectomy is associated with lower morbidity, shorter length of stay, reduced blood loss and transfusion rates, less post-operative ileus and a reduced need for analgesics. The short and medium term oncological efficacy of robotic cystectomy has been shown to be equivalent to open surgery. However, larger studies with longer follow-up are needed in order to obtain higher levels of evidence.

A comparison of overall survival and perioperative outcomes between partial and radical nephrectomy for cT1b and cT2 renal cell carcinoma-Analysis of a national cancer registry

OBJECTIVES Partial nephrectomy (PN) is the standard management of cT1a renal cell carcinoma (RCC), and there is a basis for expanding its indications to larger tumors (cT1b and cT2). We analyzed a large population-based cancer registry to compare the overall survival (OS) and perioperative outcomes in patients with cT1b and cT2 RCC undergoing PN with those undergoing radical nephrectomy (RN). MATERIALS AND METHODS Patients with cT1bN0M0 and cT2N0M0 RCC were identified from the National Cancer Database (2004-2013). Patients were classified by the surgery performed and 1:1 propensity matched based on the likelihood of receiving PN. They were then compared for OS, 30-day readmission rates and 30- and 90-day mortality. RESULTS A total of 6,072 patients underwent PN. PN was associated with better OS in cT1b tumors on multivariate analyses (OR = 0.8; 95% CI: 0.72-0.89; P<0.001). For cT2 tumors, PN was associated with better OS, however this was not statistically significant (OR = 0.8; 95% CI: 0.62-1.04; P = 0.092). Unplanned readmission at 30 days was significantly more common in patients undergoing PN (4.2%) vs. RN (2.9%) but there was no difference in 30- and 90-day mortality between the 2 groups. CONCLUSIONS PN was associated with a significantly better OS than RN for cT1b but not cT2 RCC. PN had a higher 30-day readmission rate than RN in these tumors and appropriate patient selection is crucial. These results require further validation, ideally via randomized trials.