Faculty Bibliography

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.

Background: Traditional pathology reports of prostate biopsy mainly focus on presence of carcinoma but ignore other pathologic findings such as inflammation or hyperplasia. In the era of MRI-ultrasound fusion-targeted prostate biopsy (MRF-TB), where specific MRI regions of interest (ROI) are targeted for biopsy, these benign findings should be reported as they may guide decisions on when to repeat imaging or prostate biopsy. In this study, we reviewed MRF-TB prostate biopsies reported as negative for carcinoma to identify pathologic correlates to visible ROI on prostate MRI. Design: From 2012 to2016, 1595 men underwent a total of 1813 prebiopsy prostate MRI, followed by MRF-TB at our institution. We rereviewed the prostate biopsy cores for all patients with PI-RADS 4 or 5 (PI-RADS 4/5) ROI but had no cancer detected on MRF-TB. Pathologic findings were separated into two groups: significant pathologic findings (SPF, such as inflammation, hyperplasia, ASAP/HGPIN) and no significant pathologic findings (NSPF) with or without cancer in same/adjacent site on systematic biopsy (SB). Patients with repeat MRI and follow-up MRF-TB evaluation. Results: 497 men had PI-RADS 4/5 lesions out of 1595 initial biopsies. Of these 497 men, 101 (20%) had MRF-TB negative for carcinoma. Upon review, 54 had SPF and 47 had NSPF on MRF-TB. Of 54 men with SPF on initial MRF-TB, 31 had repeat MRI, 23 of 31 men downgraded in which 16 had repeat MRF-TB with 1 had cancer detect. The other 8 of 31 men had persistent PI-RADS 4/5 lesions, 3 were detected cancer on repeat MRF-TB. Of 47 men with NSPF on initial MRF-TB, 19 had PCa in the same/ adjacent site on SB and were considered as missed on MRF-TB; of the other 28, 13 underwent repeat MRI. 8 of 13 downgraded with 0 had PCa in the repeat MRF-TB and 5 of 13 men with persistent PI-RADS 4/5 lesions, 3 had PCa detect on repeat MRF-TB. Altogether, 22/47 (47%) of the cases with NSPF in the initial MRF-TB were missed cancer. Conclusions: 1/5 of the target biopsy cases on PI-RADS 4/5 ROI had negative cancer detection. Inflammation, nodular hyperplasia and HGPIN can account for some of the cases, and those were downgraded in followup MRI usually had a negative repeat biopsy. Cases with NSPF on MRF-TB for PI-RADS 4/5 lesions are likely (47%) missed PCa, high likelihood of persistent PI-RADS 4/5 ROI on repeat MRI and PCa detection on repeat biopsy. We suggest pathology findings beside cancer should be reported on MRF-TB biopsy as they can guide decisions on repeat imagine and biopsy

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.

Introduction & Objectives: Standard of care for prostate cancer diagnosis in biopsy naive men is transrectal ultrasound guided prostate (TRUS) biopsy. Evidence is accumulating that MRI is useful in detecting clinically significant prostate cancer, and it is widely recommended after a negative biopsy. Controversy exists regarding its effectiveness before biopsy in all men. PRECISION aimed to evaluate whether multiparametric MRI and a targeted biopsy only (MRI+/-TB) was non-inferior to TRUS biopsy in the detection of clinically significant prostate cancer in biopsy naive men. Materials & Methods: PRECISION was a prospective, randomised, non-inferiority trial, carried out in 25 centres in 11 countries. 500 men were randomly allocated to 10-12 core TRUS-biopsy or MRI+/-TB. Men randomised to MRI+/-TB underwent MRI followed by targeted biopsy alone (without standard cores) if the PIRADSv2 score was >=3. MRI was either 1.5 or 3.0 T with at least a pelvic phased array coil, interpreted by a local radiologist, and image- registration technique was left to local expertise. Men with a PIRADSv2 score of 1-2 were not offered biopsy. Men in the 10-12 core TRUS-biopsy arm did not undergo pre-biopsy MRI. The primary outcome was the proportion of men diagnosed with clinically significant cancer (Gleason grade (GG) >= 3+4), with the non-inferiority margin for the difference in proportions set at -5%. Planned secondary outcomes included the proportion of men with clinically insignificant cancer (GG 3+3). Ethical approval was obtained for the study. Results: Baseline characteristics were similar in both MRI+/-TB and TRUS biopsy arms for mean age (64 vs 65), median PSA (6.8 vs 6.5), proportion of men with family history of prostate cancer (19% vs 16%) and proportion of men with abnormal digital rectal examination (14% vs 15%). Of 252 men randomised to MRI+/-TB, 71 (28%) avoided a biopsy. Clinically significant cancer was detected in 95 (38%) of 252 men in the MRI+/-TB arm compared to 64 (26%) of 248 men randomised to TRUS-biopsy (intention-to-treat analysis). Adjusting for centre effects, the absolute difference (MRI+/-TB versus TRUS-biopsy) in the proportion of men diagnosed with clinically significant prostate cancer was 11.8% (2-sided 95% CI 3.7 to 20.0; p = 0.005). The lower bound of the 95% CI for the difference is greater than -5% therefore MRI+/-TB was non-inferior to TRUS biopsy. Furthermore, the range of 95% CI was consistent with a claim of superiority of MRI+/-TB over TRUS-biopsy. MRI+/-TB also diagnosed fewer men with insignificant cancer than TRUS biopsy [23/252 (9%) vs 55/248 (22%), p<0.001]. Conclusions: Several benefits may be conferred by changing the standard of care from TRUS biopsy with standard cores alone, to MRI and targeted biopsy alone in men with suspicious MRI. These include fewer men biopsied, fewer cores taken, greater number of significant cancers diagnosed, and lower chance of diagnosing low risk cancer

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.