Piyush K. Agarwal

Treatment failure after primary and salvage therapy for prostate cancer: Likelihood, patterns of care, and outcomes

The authors report the likelihood of treatment failure and the outcomes after salvage therapy among men with prostate cancer who initially either received external‐beam radiation therapy (EBRT) or underwent radical prostatectomy (RP).

Complications After Robot-assisted Radical Cystectomy: Results from the International Robotic Cystectomy Consortium

BACKGROUND Complication reporting is highly variable and nonstandardized. Therefore, it is imperative to determine the surgical outcomes of major oncologic procedures. OBJECTIVE To describe the complications after robot-assisted radical cystectomy (RARC) using a standardized and validated reporting methodology. DESIGN, SETTING, AND PARTICIPANTS Using the International Robotic Cystectomy Consortium (IRCC) database, we identified 939 patients who underwent RARC, had available complication data, and had at least 90 d of follow-up. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Complications were analyzed and graded according to the Memorial Sloan-Kettering Cancer Center (MSKCC) system and were defined and stratified by organ system. Secondary outcomes included identification of preoperative and intraoperative variables predicting complications. Logistic regression models were used to define predictors of complications and readmission. RESULTS AND LIMITATIONS Forty-one percent (n=387) and 48% (n=448) of patients experienced a complication within 30 and 90 d of surgery, respectively. The highest grade of complication was grade 0 in 52%, grade 1-2 in 29%, and grade 3-5 in 19% patients. Gastrointestinal, infectious, and genitourinary complications were most common (27%, 23%, and 17%, respectively). On multivariable analysis, increasing age group, neoadjuvant chemotherapy, and receipt of blood transfusion were independent predictors of any and high-grade complications, respectively. Thirty and 90-d mortality was 1.3% and 4.2%, respectively. As a multi-institutional database, a disparity in patient selection, operating standards, postoperative management, and reporting of complications can be considered a major limitation of the study. CONCLUSIONS Surgical morbidity after RARC is significant when reported using a standardized reporting methodology. The majority of complications are low grade. Strict reporting of complications is necessary to advocate for radical cystectomy (RC) and helps in patient counseling.

Analysis of intracorporeal compared with extracorporeal urinary diversion after robot-assisted radical cystectomy: Results from the international robotic cystectomy consortium

BACKGROUND Intracorporeal urinary diversion (ICUD) has the potential benefits of a smaller incision, reduced pain, decreased bowel exposure, and reduced risk of fluid imbalance. OBJECTIVE To compare the perioperative outcomes of patients undergoing extracorporeal urinary diversion (ECUD) and ICUD following robot-assisted radical cystectomy (RARC). DESIGN, SETTING, AND PARTICIPANTS We reviewed the database of the International Robotic Cystectomy Consortium (IRCC) (18 international centers), with 935 patients who had undergone RARC and pelvic lymph node dissection (PLND) between 2003 and 2011. INTERVENTION All patients within the IRCC underwent RARC and PLND as indicated. The urinary diversion was performed either intracorporeally or extracorporeally. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Demographic data, perioperative outcomes, and complications in patients undergoing ICUD or ECUD were compared. All patients had at least a 90-d follow-up. The Fisher exact test was used to summarize categorical variables and the Wilcoxon rank sum test or Kruskal-Wallis test for continuous variables. RESULTS AND LIMITATIONS Of 935 patients who had RARC and PLND, 167 patients underwent ICUD (ileal conduit: 106; neobladder: 61), and 768 patients had an ECUD (ileal conduit: 570; neobladder: 198). Postoperative complications data were available for 817 patients, with a minimum follow-up of 90 d. There was no difference in age, gender, body mass index, American Society of Anesthesiologists grade, or rate of prior abdominal surgery between the groups. The operative time was equivalent (414 min), with the median hospital stay being marginally longer for the ICUD group (9 d vs 8 d, p=0.086). No difference in the reoperation rates at 30 d was noted between the groups. The 90-d complication rate was not significant between the two groups, but a trend favoring ICUD over ECUD was noted (41% vs 49%, p=0.05). Gastrointestinal complications were significantly lower in the ICUD group (p ≤ 0.001). Patients with ICUD were at a lower risk of experiencing a postoperative complication at 90 d (32%) (odds ratio: 0.68; 95% confidence interval, 0.50-0.94; p=0.02). Being a retrospective study was the main limitation. CONCLUSIONS Robot-assisted ICUD can be accomplished safely, with comparable outcomes to open urinary diversion. In this cohort, patients undergoing ICUD had a relatively lower risk of complications.

Safety Profile of Robot-Assisted Radical Prostatectomy: A Standardized Report of Complications in 3317 Patients

BACKGROUND Previous studies attempting to assess complications after robot-assisted radical prostatectomy (RARP) are limited by their small numbers, short follow-up, or lack of risk factor analysis. OBJECTIVE To document complications after RARP by strict application of standardized reporting criteria. DESIGN, SETTING, AND PARTICIPANTS Between January 2005 and December 2009, 3317 consecutive patients underwent RARP at a tertiary referral center. Median follow-up was 24.2 mo (interquartile range: 12.4-36.9). INTERVENTION Transperitoneal RARP was performed by one of five surgeons-two experienced, three beginners. MEASUREMENTS Complications were captured by exhaustive review of multiple datasets, including our prospective prostate cancer database, claims data, and electronic medical and institutional morbidity and mortality records, and reported according to the Martin-Donat criteria. Complications were stratified by type (medical/surgical), Clavien classification, and timing of onset. Multivariable analysis of factors predictive of complications was performed. RESULTS AND LIMITATIONS The median hospitalization time was 1 d. There were 368 complications in 326 patients (9.8%), including a transfusion rate of 2.2%. We detected 79 medical complications in 78 patients (2.4%) and 289 surgical complications in 264 patients (8.0%). There were 242 minor (Clavien 1-2) and 126 major (Clavien 3-5) complications. Two hundred ninety-nine (81.3%) complications occurred within 30 d, 17 (4.6%) within 31-90 d, and 52 (14.1%) after 90 d from surgery. On multivariable analysis, preoperative prostate-specific antigen values and cardiac comorbidity were predictive for medical complications, whereas age, gastroesophageal reflux disease, and biopsy Gleason score were predictive of surgical complications. Limitations of this study include representing results from a single high-volume referral center and not including the learning curve of the two most experienced surgeons. CONCLUSIONS RARP is a safe operation, with an overall complication rate of 9.8%. Most complications occurred within 30 d of surgery.

Retractile Testis—Is it Really a Normal Variant?

PURPOSE Retractile testes are thought to represent a normal variant of descended testes in prepubertal boys. We studied retractile testes to determine their natural history. MATERIALS AND METHODS We retrospectively reviewed the charts of 122 boys (mean age 5.4 years) who were referred for a suspected undescended testis and were found to have a retractile testis. A retractile testis was defined as a suprascrotal testis that could be manipulated easily into the scrotum and remained there without traction until the cremasteric reflex was induced. The boys were followed by annual examinations, which demonstrated the presence of retractile, descended (nonretractile) or undescended testes, and the presence or absence of a taut or inelastic spermatic cord in association with a retractile testis. RESULTS Of 204 retractile testes 61 (30%) descended (became nonretractile), 66 (32%) became UDTs and 77 (38%) remained retractile. Of the 62 retractile testes with a taut or inelastic spermatic cord 35 (56%) became UDTs. Of the 61 orchiopexies performed 8 (13%) showed a patent processus vaginalis. Boys in whom UDTs vs descended testes developed were a mean of 4.9 vs 6.6 years old (p = 0.001). The chance of spontaneous descent was 58% in boys 7 years or older, compared to 21% in boys younger than 7 (p <0.0001). CONCLUSIONS A retractile testis is not a normal variant. Retractile testes have a 32% risk of becoming an ascending or acquired undescended testis. The risk is higher in boys younger than 7 years old, or when the spermatic cord seems tight or inelastic. Boys with retractile testes should be monitored annually until the testes have clearly descended.

Men Presenting for Radical Prostatectomy on Preoperative Statin Therapy Have Reduced Serum Prostate Specific Antigen

PURPOSE Studies have suggested that statin (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors) medication use may decrease prostate specific antigen in healthy men. We determined the effect of preoperative statin use on total preoperative prostate specific antigen and the risk of biochemical recurrence in patients with prostate cancer presenting for radical prostatectomy. MATERIALS AND METHODS A retrospective review of 3,828 patients undergoing radical prostatectomy from January 2001 to July 2008 at our institution identified 1,031 on statin medications. We compared these 1,031 patients to the remaining 2,797 not on statins preoperatively. We evaluated differences in prostate specific antigen overall, and when patients were stratified by age specific groups, body mass index and Gleason grades on final pathology. We also investigated differences in biochemical recurrence rates. RESULTS Overall median serum prostate specific antigen was lower in patients on preoperative statins (5.0 vs 5.2 ng/ml, p = 0.002). Median prostate specific antigen was lower in men on statins with Gleason grades 7 or 8/9 disease (p <0.05). Using a multivariate logistic regression model statin therapy was associated with a 4.7% decrease in prostate specific antigen (p <0.001). Statin therapy was not associated with an overall decreased risk of biochemical recurrence (p = 0.73) at a mean followup of 26 months. CONCLUSIONS In this cohort of men presenting for radical prostatectomy serum prostate specific antigen is significantly lower in patients with prostate cancer on preoperative statins compared to those not taking these medications. Prospective studies are required to evaluate if this decrease in prostate specific antigen leads to later detection of prostate cancer or variations in oncological outcomes.

Disparities in access to care at high-volume institutions for uro-oncologic procedures

Socioeconomic status represents an established barrier to health care access. Age, sex, and race may also play a role. The authors examined whether these affect the access to high‐volume hospitals for uro‐oncologic procedures in the United States.

Impact of surgeon and volume on extended lymphadenectomy at the time of robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium (IRCC)

Lymph node dissection and its extend during robot‐assisted radical cystectomy varies based on surgeon related factors. This study reports outcomes of robot‐assisted extended lymphadenectomy based on surgeon experience in both academic and private practice settings.

Targeted therapies in urothelial carcinoma.

Purpose of review Greater understanding of the biology and genetics of urothelial carcinoma is helping to identify and define the role of molecules and pathways appropriate for novel-targeted therapies. Here, we review the targeted therapies that have been reported or are in ongoing urothelial carcinoma clinical trials, and highlight molecular targets characterized in preclinical and clinical studies. Recent findings Trials in nonmuscle-invasive bladder cancer are evaluating the role of immunotherapy and agents targeting vascular endothelial growth factor (VEGF) or fibroblast growth factor receptor-3. In muscle-invasive bladder cancer, neoadjuvant studies have focused on combining VEGF agents with chemotherapy; adjuvant studies are testing vaccines and agents targeting the human epidermal growth factor receptor 2, p53, and Hsp27. In the first-line treatment of metastatic urothelial carcinoma, tubulin, cytotoxic T-lymphocyte antigen 4, Hsp27, and p53 are novel targets in clinical trials. The majority of targeted agents studied in urothelial carcinoma are in the second-line setting; new targets include CD105, polo-like kinase-1, phosphatidylinositide 3-kinases (PI3K), transforming growth factor &bgr; receptor/activin receptor-like kinase &bgr;, estrogen receptor, and the hepatocyte growth factor receptor (HGFR or MET). Summary Development of targeted therapies for urothelial carcinoma is still in early stages, consequently there have been no major therapeutic advances to date. However, greater understanding of urothelial carcinoma and solid tumor biology has resulted in a proliferation of clinical trials that could lead to significant advances in treatment strategies.

Effect of metabolic syndrome on pathologic features of prostate cancer

OBJECTIVE The prevalence of metabolic syndrome has been increasing worldwide, however its association with prostate cancer (CaP) is unclear. We reviewed patients undergoing robot assisted radical prostatectomy (RARP) to evaluate if those with metabolic syndrome had more aggressive disease. MATERIALS AND METHODS A prospective database of patients undergoing RARP between January 2005 and December 2008 (n = 2756) was queried for components of metabolic syndrome (BMI ≥ 30 and ≥ 2 of the following: hypertension, diabetes or elevated blood glucose, and dyslipidemia; n = 357). Patients with no components of metabolic syndrome were used as controls (n = 694). Biopsy and final pathology were compared between the 2 groups using all controls, and using best-matched controls (n = 357) based on greedy matching by propensity score. RESULTS Compared with unmatched controls, metabolic syndrome patients had higher pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and higher pathologic stage (≥ T3 disease: 43% vs. 31%, P < 0.001). After controlling for confounders, those with metabolic syndrome when compared with best-matched controls had maintained the greater pathology Gleason grade (≥ 7: 78% vs. 64%, P < 0.001) and pathologic stage (≥ T3 disease: 43% vs. 32%, P < 0.001). They also had significantly greater pathologic upgrading of Gleason grade 6 adenocarcinoma found on biopsy compared with best-matched controls (63% vs. 45%, P < 0.001). On pathology, a 2-fold increase in Gleason 8 and greater was noted between patients with metabolic syndrome and best-matched controls (15% vs. 8%). CONCLUSIONS After controlling for confounders, patients with metabolic syndrome were found to have higher Gleason grade and tumor stage on final pathology and were more likely to have upgrading.