European Urology

2.1. Patient selection and technique

After institutional review board approval, we retrospectively reviewed all the prospectively collected data of the 324 consecutive patients treated with RNU at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York City between 1995 and 2008. We excluded patients treated with previous or concurrent radical cystectomy (n = 45), patients treated with preoperative chemotherapy (n = 43), patients with prior contralateral UTUC (n = 4), and patients with metastatic disease prior to RNU (n = 3). The remaining 253 patients were the subjects of the present analysis. No patient had invasive bladder tumor at the time of RNU.

Surgery was performed by genitourinary surgeons at MSKCC according to the standard criteria for RNU: dissection of the kidney with the entire length of the ureter and adjacent segment of the bladder cuff. The hilar and regional lymph nodes adjacent to the ipsilateral great vessel generally were resected along with enlarged lymph nodes if abnormal on preoperative computed tomography (CT) scans or palpable intraoperatively. Extended lymphadenectomy was not routinely performed.

Tumor location was divided into two groups based on the location (renal pelvis or ureter) of the dominant tumor as identified in the final pathologic specimen. The dominant lesion was defined as that with the highest pathologic tumor stage (pT). For multifocal tumors with the same stage, tumor size was used to define the index lesion for location classification. Thirty-seven patients had primary pelvic tumors with secondary ureteral lesions, and 18 patients had primary ureteral tumors with secondary pelvic lesions; these patients were considered for analysis based on the location of the dominant tumor.

2.2. Pathologic evaluation

All surgical specimens were processed according to standard pathologic procedures at our institution. All specimens were histologically confirmed to be UC. UTUC was defined as UC located in the renal pelvis or calices as well as tumors located within the ureter. Tumors were staged according to the 2002 American Joint Committee on Cancer–Union Internationale Contre le Cancer TNM classification. Tumor grading was assessed according to the 1998 World Health Organization/International Society of Urologic Pathology consensus classification [13] x J.I. Epstein, M.B. Amin, V.R. Reuter, F.K. Mostofi, Bladder Consensus Conference Committee. The World Health Organization/International Society of Urological Pathology consensus classification of urothelial (transitional cell) neoplasms of the urinary bladder. Am J Surg Pathol. 1998;22:1435-1448 Crossref. .

2.3. Follow-up regimen

Patients were observed every 3 mo for the first year after RNU, every 4 mo for the second year, every 6 mo from the third through fifth years, and annually thereafter. Follow-up consisted of history, physical examination, routine blood work and serum chemistry studies, urinary cytology, chest radiography, cystoscopic evaluation of the urinary bladder, and radiographic evaluation of the contralateral upper urinary tract. Since November 2001, CT urograms have been the standard imaging modality for evaluating the abdomen and pelvis for urothelial recurrence at our institution. Elective bone scans, chest CT, and magnetic resonance imaging scans were performed when clinically indicated.

Disease recurrence was defined as any documented radiograph or pathologically proven failure in the bladder, contralateral kidney, operative site, regional lymph nodes, or distant metastasis. In our analysis, we considered contralateral recurrence as metastatic recurrence. Cause of death was determined by chart review corroborated by death certificates. Most patients who were identified as having died of UTUC had progressive, widely disseminated metastases at the time of death.

2.4. Statistical methods

The Fisher exact test was used to evaluate the association between categorical variables, and the Mann-Whitney test assessed for differences in variables with a continuous distribution across dichotomous categories. Recurrence-free probabilities and CSS were estimated using Kaplan-Meier methods, with differences assessed using the log-rank test. Survival time was calculated from the date of RNU. Univariate and multivariable Cox proportional hazards regression models were used to evaluate the association between tumor location and bladder-only recurrence, nonbladder recurrence (contralateral kidney, operative site, regional lymph nodes, or distant metastasis), and any recurrence as well as cancer-specific mortality after RNU. Patients without disease recurrence were censored at the date of their last follow-up. All reported p values are two-sided, and significance was set at p < 0.05. Statistical analyses were conducted using Stata v.8.0 (StataCorp, College Station, TX, USA).