Karakiewicz, Pierre I.

ObjectivesTechnical limitations of ureteroscopic (URS) biopsy has been considered responsible for substantial upgrading rate in upper tract urothelial carcinoma (UTUC). However, the impact of tumor specific factors for upgrading remain uninvestigated.MethodsPatients who underwent URS biopsy were included between 2005 and 2020 at 13 institutions. We assessed the prognostic impact of upgrading (low‐grade on URS biopsy) versus same grade (high‐grade on URS biopsy) for high‐grade UTUC tumors on radical nephroureterectomy (RNU) specimens.ResultsThis study included 371 patients, of whom 112 (30%) and 259 (70%) were biopsy‐based low‐ and high‐grade tumors, respectively. Median follow‐up was 27.3 months. Patients with high‐grade biopsy were more likely to harbor unfavorable pathologic features, such as lymphovascular invasion (p < 0.001) and positive lymph nodes (LNs; p < 0.001). On multivariable analyses adjusting for the established risk factors, high‐grade biopsy was significantly associated with worse overall (hazard ratio [HR] 1.74; 95% confidence interval [CI], 1.10–2.75; p = 0.018), cancer‐specific (HR 1.94; 95% CI, 1.07–3.52; p = 0.03), and recurrence‐free survival (HR 1.80; 95% CI, 1.13–2.87; p = 0.013). In subgroup analyses of patients with pT2‐T4 and/or positive LN, its significant association retained. Furthermore, high‐grade biopsy in clinically non‐muscle invasive disease significantly predicted upstaging to final pathologically advanced disease (≥pT2) compared to low‐grade biopsy.ConclusionsHigh tumor grade on URS biopsy is associated with features of biologically and clinically aggressive UTUC tumors. URS low‐grade UTUC that becomes upgraded to high‐grade might carry a better prognosis than high‐grade UTUC on URS. Tumor specific factors are likely to be responsible for upgrading to high‐grade on RNU.

AbstractObjectiveTo evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa).Patients and methodsThe study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (<0.5 ng/ml), low (0.5–0.99 ng/ml), moderate (1–1.5 ng/ml) and high (>1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value.ResultsMedian [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non‐linear relationship between PSA level at sLND and the 12‐month CR‐free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml.ConclusionsIn case of PET‐detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short‐term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga‐PSMA PET in biochemical recurrent PCa.

Background: To assess the differential effect of robotic assisted radical cystectomy (RARC) versus open radical cystectomy (ORC) on survival outcomes in matched analyses performed on a large multicentric cohort. Methods: The study included 9757 patients with urothelial bladder cancer (BCa) treated in a consecutive manner at each of 25 institutions. All patients underwent radical cystectomy with bilateral pelvic lymphadenectomy. To adjust for potential selection bias, propensity score matching 2:1 was performed with two ORC patients matched to one RARC patient. The propensity-matched cohort included 1374 patients. Multivariable competing risk analyses accounting for death of other causes, tested association of surgical technique with recurrence and cancer specific mortality (CSM), before and after propensity score matching. Results: Overall, 767 (7.8%) patients underwent RARC and 8990 (92.2%) ORC. The median follow-up before and after propensity matching was 81 and 102 months, respectively. In the overall population, the 3-year recurrence rates and CSM were 37% vs. 26% and 34% vs. 24% for ORC vs. RARC (all p values > 0.1), respectively. On multivariable Cox regression analyses, RARC and ORC had similar recurrence and CSM rates before and after matching (all p values > 0.1). Conclusions: Patients treated with RARC and ORC have similar survival outcomes. This data is helpful in consulting patients until long term survival outcomes of level one evidence is available.

334 Background: Radical cystectomy (RC) represents the standard of care for patients with muscle-invasive urothelial carcinoma of the urinary bladder (UCUB). Alternative organ-conserving treatments such as chemotherapy and/or radiotherapy have gained interest. We sought to compare survival outcomes of patients according to treatment modalities, in a stage-for-stage analysis. Methods: We relied on the Surveillance, Epidemiology, and End Results Medicare-linked database to identify 12,950 patients diagnosed with T2–T4a N0/x M0 UCUB between years 1992 and 2009. Treatment types include RC (n=5207), chemotherapy/radiation (n=2,669), and surveillance (n=5,074). Following instrumental variable analysis, Cox- and competing-risks regression analyses were performed for prediction of overall survival (OS) and cancer-specific mortality (CSM), respectively. All analyses were stratified according to disease stage (T2, T3, T4a). Results: After adjusting for potential confounders, OS was more favorable for RC relative to chemotherapy/radiation (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.02–2.40) or surveillance (HR: 1.82, 95% CI: 1.20–2.78) in patients with T2 UCUB. For the same stage, CSM rates were lower in the surgery group compared to chemotherapy/radiation (HR: 2.05, 95% CI: 1.14–3.67) or surveillance (HR: 1.95, 95% CI: 1.09–3.48). When analyses focused on individuals with more advanced disease (T3–T4a), no statistically significant difference was observed between chemotherapy/radiation relative to RC for both OS and CSM. Conclusions: In the current retrospective population-based cohort, RC was associated with improved survival outcomes relative to its alternative treatment counterparts. However, this effect was only observable in patients with T2 disease. Conversely, no difference between chemotherapy/radiation vs. surgery was noted in patients with more advanced disease stage.

BACKGROUNDA new prostate cancer (PCa) grading system (namely, Gleason score‐GS‐ ≤6 vs. 3 + 4 vs. 4 + 3 vs. 8 vs. ≥9) was recently proposed and assessed on biochemical recurrence (BCR) showing improved predictive abilities compared to the commonly used three‐tier system (GS ≤6 vs. 7 vs. ≥8). We assessed the predictive ability of the five‐tier grade group (GG) system on harder clinical endpoint, namely clinical recurrence (CR).METHODSBetween 2005 and 2014, 9,728 clinically localized PCa patients were treated with radical prostatectomy (RP) at two tertiary referral centers. Kaplan–Meier curves, multivariable Cox regression analyses, and concordance index (C‐index) were used to assess CR after treatment according to four Gleason grade classifications at biopsy and RP: Group 1: ≤6 versus 7 versus ≥8; Group 2: ≤6 versus 3 + 4 vs. 4 + 3 versus ≥8; Group 3: ≤6 versus 7 versus 8 versus ≥9; Group 4: ≤6 versus 3 + 4 versus 4 + 3 versus 8 versus ≥9. Same analyses were repeated in patients who had BCR (n = 1,624). Decision curve analyses were performed to evaluate and compare the net benefit associated with the use of the four Gleason grade classifications.RESULTSOverall, 443 (4.6%) patients had CR. The hazard ratio of the GS 3 + 4, 4 + 3, 8, and ≥9 relative to GS ≤6 were 3.63, 5.93, 11.44, 18.08 and 4.93, 9.99, 15.31 and 25.12 in the pre‐ and post‐treatment models, respectively. The C‐index of the five‐tier GG system was slightly higher relative to the other 3 Gleason grade classifications both in the pre‐ (range: 0.001–0.006) and post‐treatment models (range: 0–0.008). Similar findings were observed when we focused our analyses in patients with BCR after RP. The use of the five‐tier GG system did not result into higher net‐benefit relative to the other three Gleason grade classifications.CONCLUSIONSThe difference in accuracy between the five‐tier GG system and the other Gleason grade classifications, using CR as an endpoint, is clinically negligible. Current evidence suggests that the five‐tier GG system represents a simplified user‐friendly scheme available for patient counseling rather than a new histopathological diagnostic system that improves the prediction of CR. Prostate 77:263–273, 2017. © 2016 Wiley Periodicals, Inc.

Objective To determine the association between peri‐operative blood transfusion ( PBT ) and oncological outcomes in a large multi‐institutional cohort of patients undergoing radical cystectomy ( RC ) for urothelial carcinoma of the bladder ( UCB ). Patients and Methods We conducted a retrospective analysis of 2895 patients treated with RC for UCB . Univariable and multivariable C ox regression models were used to analyse the effect of PBT administration on disease recurrence, cancer‐specific mortality, and any‐cause mortality. Results Patients' median (interquartile range [ IQR ]) age was 67 (60, 73) years and the median ( IQR ) follow‐up was 36.1 (15, 84) months. Patients who received PBT were more likely to have advanced disease ( P < 0.001), high grade tumours ( P = 0.047) and nodal metastasis ( P = 0.004). PBT was associated with a higher risk of disease recurrence ( P = 0.003), cancer‐specific mortality ( P = 0.017), and any‐cause mortality ( P = 0.010) in univariable, but not multivariable, analyses ( P > 0.05). In multivariable analyses, pathological tumour stage, pathological nodal stage, soft tissue surgical margin, lymphovascular invasion and administration of adjuvant chemotherapy were independent predictors of disease recurrence, cancer‐specific mortality and any‐cause mortality (all P values <0.002). Conclusions Patients with UCB who underwent RC and received PBT had a greater risk of disease recurrence, cancer‐specific mortality and any‐cause mortality in univariable, but not multivariable, analysis. Although the greater need for PBT with more advanced disease is probably caused by a number of factors, including surgical and cancer‐related factors, the present analysis showed that the disease characteristics rather than need for PBT led to worse outcomes.

BACKGROUNDApproximately 1.7 million individuals per year are affected with health care‐associated infections (HAIs) in the United States. The authors examined trends in the incidence of HAI after major cancer surgery (MCS) and risk factors for HAI to describe the effects of HAI on mortality after MCS.METHODSPatients undergoing 1 of 8 MCS procedures within the Nationwide Inpatient Sample between 1999 and 2009 were identified (n = 2,502,686). Generalized linear regression models were used to estimate the impact of the primary predictors (procedure type, age, sex, race, insurance status, Charlson comorbidity index, hospital volume, and hospital bed size) on the odds of HAI and in‐hospital mortality. Trends in incidence were evaluated with linear regression.RESULTSOverall, MCS‐associated HAI incidence increased 2.7% per year (P < .001), whereas mortality decreased 1.3% per year (P < .001). Male gender (odds ratio [OR], 1.12, 95% confidence interval [CI], 1.10‐1.14), advancing age (OR, 1.02; 95% CI, 1.02‐1.02), black race (OR, 1.26; 95% CI, 1.21‐1.31), ≥1 comorbidities (OR, from 1.08 [95% CI, 1.04‐1.13] to 1.31 [95% CI, 1.27‐1.35]), and nonprivate insurance (OR, from 1.18 [95% CI, 1.15‐1.22] to 1.67 [95% CI, 1.59‐1.76]) were associated with an increased odds of HAI on multivariable analysis. Conversely, increasing hospital volume was associated with lower odds of HAI (OR, 0.999; 95% CI, 0.99‐0.99). Patients with MCS‐associated HAI had increased odds of mortality (OR, 8.66; 95% CI, 8.51‐8.82).CONCLUSIONSBetween 1999 and 2009, the incidence of MCS‐associated HAI events increased; however, HAI‐associated mortality decreased. That said, significant disparities exist in the hospital and demographic attributes associated with MCS‐associated HAI, with attendant health policy implications. Moreover, HAI remains detrimentally linked to mortality during hospitalization. Cancer 2013;119:2317–2324. © 2013 American Cancer Society.