Faculty Bibliography

BACKGROUND:The number of prostate biopsy cores that need to be taken from each magnetic resonance imaging (MRI) region of interest (ROI) to optimize sampling while minimizing overdetection has not yet been clearly elucidated. OBJECTIVE:To characterize the incremental value of additional MRI-ultrasound (US) fusion targeted biopsy cores in defining the optimal number when planning biopsy and to predict men who might benefit from more than two targeted cores. DESIGN, SETTING, AND PARTICIPANTS/METHODS:This was a retrospective cohort study of MRI-US fusion targeted biopsies between 2015 and 2017. INTERVENTION/METHODS:MRI-US fusion targeted biopsy in which four biopsy cores were directed to each MRI-targeted ROI. OUTCOMES MEASUREMENTS AND STATISTICAL ANALYSIS/UNASSIGNED:The MRI-targeted cores representing the first highest Gleason core (FHGC) and first clinically significant cancer core (FCSC; GS≥3+4) were evaluated. We analyzed the frequency of FHGC and FCSC among cores 1-4 and created a logistic regression model to predict FHGC >2. The number of unnecessary cores avoided and the number of malignancies missed for each Gleason grade were calculated via clinical utility analysis. The level of agreement between biopsy and prostatectomy Gleason scores was evaluated using Cohen's κ. RESULTS AND LIMITATIONS/CONCLUSIONS:A total of 479 patients underwent fusion targeted biopsy with four individual cores, with 615 ROIs biopsied. Among those, FHGC was core 1 in 477 (76.8%), core 2 in 69 (11.6%), core 3 in 48 (7.6%), and core 4 in 24 men (4.0%) with any cancer. Among men with clinically significant cancer, FCSC was core 1 in 191 (77.8%), core 2 in 26 (11.1%), core 3 in 17 (6.2%), and core 4 in 11 samples (4.9%). In comparison to men with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 5, patients were significantly less likely to have FHGS >2 if they had PI-RADS 4 (odds ratio [OR] 0.287; p=0.006), PI-RADS 3 (OR 0.284; p=0.006), or PI-RADS 2 (OR 0.343; p=0.015). Study limitations include a single-institution experience and the retrospective nature. CONCLUSIONS:Cores 1-2 represented FHGC 88.4% and FCSC 88.9% of the time. A PI-RADS score of 5 independently predicted FHGC >2. Although the majority of cancers in our study were appropriately characterized in the first two biopsy cores, there remains a proportion of men who would benefit from additional cores. PATIENT SUMMARY/UNASSIGNED:In men who undergo magnetic resonance imaging-ultrasound fusion targeted biopsy, the first two biopsy cores diagnose the majority of clinically significant cancers. However, there remains a proportion of men who would benefit from additional cores.

INTRODUCTION/BACKGROUND:Nutritional status has been increasingly recognized as an important predictor of prognosis and surgical outcomes for cancer patients. We evaluated the effect of preoperative malnutrition on the development of surgical complications and mortality after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS/METHODS:Using data from the American College of Surgeons National Surgical Quality Improvement Program, we evaluated the association of poor nutritional status with 30-day postoperative complications and overall mortality after RNU from 2005 to 2015. The preoperative variables suggestive of poor nutritional status included hypoalbuminemia (< 3.5 g/dL), weight loss within 6 months before surgery (> 10%), and a low body mass index. RESULTS:A total of 1200 patients were identified who had undergone RNU for UTUC. The overall complication rate was 20.5% (n = 246), and mortality rate was 1.75% (n = 21). On univariate analysis, patients who experienced a postoperative complication were more likely to have hypoalbuminemia (25.0% vs. 11.4%; P < .001) and weight loss (3.7% vs. 1.0%; P = .003). After controlling for baseline characteristics and comorbidities, hypoalbuminemia was found to be a significant independent predictor of postoperative complications (odds ratio, 2.09; 95% confidence interval, 1.29-3.38; P = .003). Hypoalbuminemia was also a significant independent predictor of mortality (odds ratio, 4.31; 95% confidence interval, 1.45-12.79; P = .008) on multivariable regression analysis. CONCLUSION/CONCLUSIONS:Our results have shown that hypoalbuminemia is a significant predictor of surgical complications and mortality after RNU for UTUC. This finding supports the importance of patients' preoperative nutritional status in this population and suggests that effective nutritional interventions in the preoperative setting could improve patient outcomes.

BACKGROUND:The American Society of Anesthesiologists physical status classification system, modified Charlson Comorbidity Index (mCCI), and modified Frailty Index have been associated with complications after urologic surgery. No study has compared the predictive performance of these indexes for postoperative complications after radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS/METHODS:Data from 1516 patients undergoing elective RC for bladder cancer were extracted from the 2005 to 2011 American College of Surgeons National Surgical Quality Improvement Program for a retrospective review. The perioperative outcome variables assessed were occurrence of minor adverse events, severe adverse events, infectious adverse events, any adverse event, extended length of hospital stay, discharge to a higher level of care, and mortality. Patient comorbidity indexes and demographic data were assessed for their discriminative ability in predicting perioperative adverse outcomes using an area under the curve (AUC) analysis from the receiver operating characteristic curves. RESULTS:The most predictive comorbidity index for any adverse event was the mCCI (AUC, 0.511). The demographic factors were the body mass index (BMI; AUC, 0.519) and sex (AUC, 0.519). However, the overall performance for all predictive indexes was poor for any adverse event (AUC < 0.52). Combining the most predictive demographic factor (BMI) and comorbidity index (mCCI) resulted in incremental improvements in discriminative ability compared with that for the individual outcome variables. CONCLUSION/CONCLUSIONS:For RC, easily obtained patient mCCI, BMI, and sex have overall similar discriminative abilities for perioperative adverse outcomes compared with the tabulated indexes, which are more difficult to implement in clinical practice. However, both the demographic factors and the comorbidity indexes had poor discriminative ability for adverse events.

Purpose Neoadjuvant chemotherapy followed by radical cystectomy (RC) is a standard of care for the management of muscle-invasive bladder cancer (MIBC). Dose-dense cisplatin-based regimens have yielded favorable outcomes compared with standard-dose chemotherapy, yet the optimal neoadjuvant regimen remains undefined. We assessed the efficacy and tolerability of six cycles of neoadjuvant dose-dense gemcitabine and cisplatin (ddGC) in patients with MIBC. Patients and Methods In this prospective, multicenter phase II study, patients received ddGC (gemcitabine 2,500 mg/m² on day 1 and cisplatin 35 mg/m² on days 1 and 2) every 2 weeks for 6 cycles followed by RC. The primary end point was pathologic downstaging to non-muscle-invasive disease (< pT2N0). Patients who did not undergo RC were deemed nonresponders. Pretreatment tumors underwent next-generation sequencing to identify predictors of chemosensitivity. Results Forty-nine patients were enrolled from three institutions. The primary end point was met, with 57% of 46 evaluable patients downstaged to < pT2N0. Pathologic response correlated with improved recurrence-free survival and overall survival. Nineteen patients (39%) required toxicity-related dose modifications. Sixty-seven percent of patients completed all six planned cycles. No patient failed to undergo RC as a result of chemotherapy-associated toxicities. The most frequent treatment-related toxicity was anemia (12%; grade 3). The presence of a presumed deleterious DNA damage response (DDR) gene alteration was associated with chemosensitivity (positive predictive value for < pT2N0 [89%]). No patient with a deleterious DDR gene alteration has experienced recurrence at a median follow-up of 2 years. Conclusion Six cycles of ddGC is an active, well-tolerated neoadjuvant regimen for the treatment of patients with MIBC. The presence of a putative deleterious DDR gene alteration in pretreatment tumor tissue strongly predicted for chemosensitivity, durable response, and superior long-term survival.

Imaging is critically important for the diagnosis, staging, and management of men with high-risk prostate cancer. Conventional imaging modalities, including computed tomography and radionuclide bone scan have been employed for local and metastatic staging, but their performance has generally been poor. Sodium fluoride positron emission tomography is recommended when there is high suspicion for bone metastases despite a negative or indeterminate bone scan. Magnetic resonance imaging has advantages in local staging but its value depends on the extent of disease. Whole body positron emission tomography/magnetic resonance imaging could provide both local and distant staging although the technology is not yet widely disseminated. None of the existing positron emission tomography agents are recommended in practice guidelines, however, among them, prostate specific membrane antigen-based tracers seem to hold the most promise based on sensitivity and specificity.