Mari, Andrea

Background: Although previous literature shows tumor location as a prognostic factor in upper tract urothelial carcinoma (UTUC), there remains uninvestigated regarding the impact of tumor location on grade concordance and discrepancies between ureteroscopic (URS) biopsy and final radical nephroureterectomy (RNU) pathology. Methods: In this international study, we retrospectively reviewed the records of 1,498 patients with UTUC who underwent diagnostic URS with concomitant biopsy followed by RNU between 2005 and 2020. Tumor location was divided into four sections: the calyceal-pelvic system, proximal ureter, middle ureter, and distal ureter. Patients with multifocal tumors were excluded from the study. We performed multiple comparison tests and logistic regression analyses. Results: Overall, 1,154 patients were included; 54.4% of those with low-grade URS biopsies were upgraded on RNU. In the multiple comparison tests, middle ureter tumors exhibited the highest probability of upgrading, meanwhile pelvicalyceal tumors exhibited the lowest probability of upgrading (73.7% vs 48.5%, p = 0.007). Downgrading was comparable across all tumor locations. On multivariate analyses, middle ureteral location was significantly associated with a low probability of grade concordance (odds ratio [OR] 0.59; 95% confidence interval [CI], 0.35–1.00; p = 0.049) and an increased risk of upgrading (OR 2.80; 95% CI, 1.20–6.52; p = 0.017). The discordance did not vary regardless of caliceal location, including the lower calyx. Conclusions: Middle ureteral tumors diagnosed to be low grade had a high probability to be undergraded. Our data can inform providers and their patients regarding the likelihood of undergrading according to tumor location, facilitating patient counseling and shared decision making regarding the choice of kidney sparing vs RNU.

Objective To investigate the optimal number of induction chemotherapy cycles needed to achieve a pathological response in patients with clinically lymph node‐positive (cN+) bladder cancer (BCa) who received three or four cycles of induction chemotherapy followed by consolidative radical cystectomy (RC) with pelvic lymph node dissection. Patients and Methods We included 388 patients who received three or four cycles of cisplatin/gemcitabine or (dose‐dense) methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC), followed by consolidative RC for cTanyN1–3M0 BCa. We compared pathological complete (pCR = ypT0N0) and objective response (pOR = yp ≤T1N0) between treatment groups. Predictors of pCR and/or pOR were assessed using uni‐ and multivariable logistic regression analysis. The secondary endpoints were overall (OS) and cancer‐specific survival (CSS). We evaluated the association between the number of induction chemotherapy cycles administered and survival outcomes on multivariable Cox regression. Results Overall, 101 and 287 patients received three or four cycles of induction chemotherapy, respectively. Of these, 72 (19%) and 128 (33%) achieved pCR and pOR response, respectively. The pCR (20%, 18%) and pOR (40%, 31%) rates did not differ significantly between patients receiving three or four cycles ( P > 0.05). The number of cycles was not associated with pCR or pOR on multivariable logistic regression analyses. The 2‐year OS estimates were 63% (95% confidence interval [CI] 0.53–0.74) and 63% (95% CI 0.58–0.7) for patients receiving three or four cycles, respectively. Receiving three vs four cycles was not associated with OS and CSS on uni‐ or multivariable Cox regression analyses. Conclusion Pathological response and survival outcomes did not differ between administering three or four induction chemotherapy cycles in patients with cN+ BCa. A fewer cycles (minimum three) may be oncologically sufficient in patients with cN+ BCa, while decreasing the wait for definitive local therapy in those patients who end up without a response to chemotherapy. This warrants further validation.

475 Background: Emerging evidence supports use of neoadjuvant chemotherapy (NAC) prior to radical nephroureterectomy (RNU) for appropriately selected patients with upper tract urothelial carcinoma (UTUC). However, oncologic outcomes have not been well characterized for patients with residual muscle-invasive disease after NAC. Methods: We used a multi-institutional cohort from 24 centers in the U.S., Europe, and Japan to retrospectively identify patients who underwent RNU for UTUC from 1985-2022 and had high-grade muscle-invasive disease. We stratified the cohort based on receipt of NAC (>ypT2 vs. >pT2). Exclusion criteria included receipt of adjuvant chemotherapy, concurrent cystectomy with RNU, and distant metastatic disease. Baseline characteristics were compared between groups. Kaplan-Meier survival analysis with log-rank test was used to compare differences in recurrence-free survival (RFS), overall survival (OS), and cancer-specific survival (CSS). Multivariable Cox regression and Fine-Gray competing risk regression were used to determine predictors of these outcomes. Results: A total of 1,233 patients were included, 62 of whom received NAC prior to RNU. A platinum-based regimen was used in 90% of NAC recipients, and the median number of cycles administered was 4 (IQR: 3-5). Median follow-up time among all patients was 22 months (IQR: 8-47 mo.). NAC recipients were more likely to have pathologic node positivity (35% vs. 13%) and less likely to have positive tumor margins (8% vs. 28%). On Kaplan-Meier analysis, NAC recipients with residual >ypT2 disease had poorer outcomes than those with >pT2 disease (2-year RFS [NAC vs. no NAC]: 52% vs. 80%, p<0.001; 2-year OS: 60% vs. 78%, p=0.003; 2-year CSS: 61% vs. 86%, p<0.001). Multivariable analyses also showed a statistically significant association between residual muscle-invasive disease after NAC and poorer RFS, OS, and CSS (Table). Conclusions: NAC recipients with >ypT2 disease at RNU after exhibit poorer outcomes than stage-matched chemotherapy naïve counterparts. This may reflect effects of occult micrometastatic disease or chemoresistant primary tumors in non-responders. Our data highlight the need to improve prospective identification of candidates most likely to respond to NAC prior to RNU for UTUC in order to maximize its therapeutic benefit. [Table: see text]

Objectives: To identify correlates of survival and perioperative outcomes of upper tract urothelial carcinoma (UTUC) patients undergoing open (ORNU), laparoscopic (LRNU), and robotic (RRNU) radical nephroureterectomy (RNU). Methods: We conducted a retrospective, multicenter study that included non-metastatic UTUC patients who underwent RNU between 1990–2020. Multiple imputation by chained equations was used to impute missing data. Patients were divided into three groups based on their surgical treatment and were adjusted by 1:1:1 propensity score matching (PSM). Survival outcomes per group were estimated for recurrence-free survival (RFS), bladder recurrence-free survival (BRFS), cancer-specific survival (CSS), and overall survival (OS). Perioperative outcomes: Intraoperative blood loss, hospital length of stay (LOS), and overall (OPC) and major postoperative complications (MPCs; defined as Clavien–Dindo > 3) were assessed between groups. Results: Of the 2434 patients included, 756 remained after PSM with 252 in each group. The three groups had similar baseline clinicopathological characteristics. The median follow-up was 32 months. Kaplan–Meier and log-rank tests demonstrated similar RFS, CSS, and OS between groups. BRFS was found to be superior with ORNU. Using multivariable regression analyses, LRNU and RRNU were independently associated with worse BRFS (HR 1.66, 95% CI 1.22–2.28, p = 0.001 and HR 1.73, 95%CI 1.22–2.47, p = 0.002, respectively). LRNU and RRNU were associated with a significantly shorter LOS (beta −1.1, 95% CI −2.2–0.02, p = 0.047 and beta −6.1, 95% CI −7.2–5.0, p < 0.001, respectively) and fewer MPCs (OR 0.5, 95% CI 0.31–0.79, p = 0.003 and OR 0.27, 95% CI 0.16–0.46, p < 0.001, respectively). Conclusions: In this large international cohort, we demonstrated similar RFS, CSS, and OS among ORNU, LRNU, and RRNU. However, LRNU and RRNU were associated with significantly worse BRFS, but a shorter LOS and fewer MPCs.

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.

Background: Measuring quality of care indicators is important for clinicians and decision making in health care to improve patient outcomes. Objective: The primary objective was to identify quality of care indicators for patients with upper tract urothelial carcinoma (UTUC) and to validate these in an international cohort treated with radical nephroureterectomy (RNU). The secondary objective was to assess the factors associated with failure to validate the pentafecta. Design: We performed a retrospective multicenter study of patients treated with RNU for EAU high-risk (HR) UTUC. Outcome measurements and statistical analysis: Five quality indicators were consensually approved, including a negative surgical margin, a complete bladder-cuff resection, the absence of hematological complications, the absence of major complications, and the absence of a 12-month postoperative recurrence. After multiple imputations and propensity-score matching, log-rank tests and a Cox regression were used to assess the survival outcomes. Logistic regression analyses assessed predictors for pentafecta failure. Results: Among the 1718 included patients, 844 (49%) achieved the pentafecta. The median follow-up was 31 months. Patients who achieved the pentafecta had superior 5-year overall- (OS) and cancer-specific survival (CSS) compared to those who did not (68.7 vs. 50.1% and 79.8 vs. 62.7%, respectively, all p < 0.001). On multivariable analyses, achieving the pentafecta was associated with improved recurrence-free survival (RFS), CSS, and OS. No preoperative clinical factors predicted a failure to validate the pentafecta. Conclusions: Establishing quality indicators for UTUC may help define prognosis and improve patient care. We propose a pentafecta quality criteria in RNU patients. Approximately half of the patients evaluated herein reached this endpoint, which in turn was independently associated with survival outcomes. Extended validation is needed.