Pathologic staging of renal cell carcinoma: significance of tumor classification with the 1997 TNM staging system.

BACKGROUND: The TNM staging system for renal cell carcinoma was revised by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer (UICC) in 1997. The 1997 TNM staging system for renal cell carcinoma reclassifies tumors using criteria for size and for extent of renal vein/vena cava involvement that are different from the criteria used in the 1987 staging system. The current study investigated the prognostic significance of tumor classification and other factors using the new staging system. METHODS: Records from 1547 renal cell carcinoma patients (1039 males and 508 females; mean age, 63.4 years; mean follow-up, 7.1 years) who underwent surgical resection between 1970 and 1998 were analyzed retrospectively. Tumors were staged using the 1987 and 1997 TNM criteria, and Kaplan-Meier estimates of survival and disease recurrence were compared for both staging systems. The Peto-Peto log rank test and the generalized Wilcoxon test were used to assess univariate significance of prognostic factors on survival. Cox proportional hazards regression analysis was then completed to assess the significance of the revised staging system. RESULTS: Tumor classification using the 1987 TNM staging system (P = 0.0001) and the 1997 TNM staging system (P = 0.0001) was a significant predictor of cause specific survival. Using 1997 TNM staging criteria, 641 patients were reclassified from the T2 classification to the T1 classification, 114 patients were reclassified from the T3c classification to the T3b classification, 11 patients were reclassified from the T4b classification to the T3c classification, and 3 patients were reclassified from the T4b classification to the T3b classification. Patients with reclassified tumors had outcomes similar to patients with tumors that remained in the same tumor classification. Patient stratification was improved using the new staging system. Prognostic discrimination for cause specific survival at 10 years was noted for the 1987 and 1997 TNM classifications (T1, 97% vs. 91%; T2, 84% vs. 70%; T3a, 53% vs. 53%; T3b, 48% vs. 42%; and T3c, 29% vs. 43%). CONCLUSIONS: The revised classification of renal cell carcinoma was a significant predictor of cause specific survival for the cohort of patients described in this report. Using the new system, the stratification of patients was improved. Patients who had their tumors reclassified as a result of the new staging system had outcomes similar to those of patients who had tumors that remained in the same classification. Based on an analysis of this cohort, tumor classification is valid, and the T1 subclassification is warranted. However, additional revision may be required to optimize staging.

Outcome of isolated renal cell carcinoma fossa recurrence after nephrectomy.

PURPOSE: Local recurrence of renal cell carcinoma in the renal fossa after complete radical nephrectomy is uncommon. We characterize and determine outcome in a small subset of patients. MATERIALS AND METHODS: From 1970 to 1998 the incidence of isolated renal bed recurrence among 1,737 T1-3N0M0 unilateral nephrectomy cases was 1. 8% (standard error [SE] 0.4) at 5 years. There were 30 patients in whom isolated local fossa carcinoma recurred after complete radical nephrectomy without evidence of metastatic disease. Patients with any nodal involvement at radical nephrectomy were excluded from study as were those who had undergone any form of partial nephrectomy. Patient charts were reviewed for clinical presentation, stage, treatment, development of metastatic disease and survival. Pathological stage was assigned according to the 1997 TNM staging system. Recurrence was identified in 12 (40%) patients during routine followup and the remaining 18 (60%) presented with symptoms related to the recurrent tumor. Patients were divided into 3 treatment groups of observation (9), therapy excluding surgical extirpation (11) and complete surgical resection alone or in conjunction with additional therapy (10). Mean time from local recurrence to development of metastatic disease was calculated. Survival from local recurrence to overall death and disease specific death was estimated using the Kaplan-Meier method. Survival curves for the different treatment groups were then compared. RESULTS: There were 30 patients identified with an ipsilateral renal fossa recurrence of renal cell carcinoma after complete nephrectomy in the absence of disseminated disease. Mean followup was 3.3 years (range 0.006 to 14.8) and no patient was lost to followup. The T stage of the primary tumor was T1/T2 in 13 cases, T3a in 4, T3b in 12, and T3c in 1, and all were node negative. Mean time to metastasis was 1. 6 years (range 0.006 to 7.3) in the 19 patients who had documented interval metastatic disease after local recurrence. There were 26 deaths, of which 25 were disease specific. Estimated overall crude and cause specific survival at 1 and 5 years was 66% and 28%, respectively. Calculating survival among symptomatic and asymptomatic patients revealed no discernible difference in outcome (p = 0.94). The 5-year survival rate with surgical resection was 51% (SE 18) compared to 18% (12) treated with adjuvant medical therapy and only 13% (12) with observation alone. The differences in cause specific survival were significant (p

Operation for partial atrioventricular septal defect: a forty-year review.

BACKGROUND: We describe the long-term outcome of repair of partial atrioventricular septal defect by determining the rates of survival, reoperation, and occurrence of left atrioventricular valve regurgitation, left atrioventricular valve stenosis, left ventricular outflow tract obstruction, and arrhythmia. METHODS: We studied 334 patients who underwent repair of partial atrioventricular septal defect before 1995. RESULTS: The 30-day and 5-, 10-, 20-, and 40-year survival were 98%, 94%, 93%, 87%, and 76%, respectively. Closure of the left atrioventricular valve cleft (P =. 03) and age less than 20 years at operation (P <.001) were associated with better survival. Reoperation was performed for 38 patients (11%). Repair of residual/recurrent left atrioventricular valve regurgitation or stenosis was the most common reason for reoperation. Left ventricular outflow tract obstruction occurred in 36 patients, and 7 patients underwent reoperation to relieve this obstruction. Supraventricular arrhythmias were observed in 58 patients (16%) after the operation. Supraventricular arrhythmias increased with increasing age at primary operation (P =.001). Complete atrioventricular block occurred in 9 patients (3%). Permanent pacemakers were implanted in 11 patients. CONCLUSIONS: Long-term survival after repair of partial atrioventricular septal defect is good. It is important to close the cleft in the left atrioventricular valve. Reoperation for persistent or recurrent left atrioventricular valve malfunction and relief of left ventricular outflow tract obstruction is necessary in approximately 11% of patients.

Cancer heterogeneity and its biologic implications in the grading of urothelial carcinoma.

BACKGROUND: Urothelial carcinoma of the bladder often contains areas with different histologic grades. The influence of cancer heterogeneity on grading and its relation to patient outcome is uncertain. METHODS: The study group consisted of 164 patients with Ta urothelial carcinoma diagnosed at the Mayo Clinic between 1985 and 1986. None had previous or coexistent urothelial carcinoma in situ or invasive carcinoma. The primary (most common) and secondary (second most common if at least 5% of the cancer) patterns of cancer growth were graded by the newly proposed World Health Organization and International Society of Urological Pathology (WHO/ISUP) grading system. Scores of 1, 2, and 3 were assigned to urothelial neoplasms of low malignant potential (LMP), low grade urothelial carcinoma, and high grade urothelial carcinoma, respectively. The mean follow-up was 7.7 years (range, 0-13.3 years; median, 9.2 years). Progression was defined as the development of invasive carcinoma, distant metastasis, or death due to bladder carcinoma. RESULTS: Patient ages ranged from 36 to 96 years (mean, 69 years), and the male-to-female ratio was 4:1. Disease progression developed in 32 patients during a mean follow-up of 7.7 years. The mean interval from diagnosis to progression was 3.1 years (range, 0.01-8.7 years). Progression free survival was 82%, 77%, and 76% at 5, 7, and 10 years, respectively. Primary and secondary grades were different for 52 patients (32%). Based on the worst grade, 19 patients (12%) had urothelial neoplasms of low malignant potential (LMP), 92 (56%) had low grade carcinoma, and 53 (32%) had high grade carcinoma. Histologic grades based on worst, primary, secondary, and combined primary and secondary grades were all significant for predicting progression (P = 0.0009, 0.0004, 0.001, and 0.0001, respectively). Seven-year progression free survival rates for patients with LMP, low grade, and high grade carcinoma (based on worst grade) were 93%, 82%, and 61%, respectively; for patients with combined scores of 2, 3, 4, 5, and 6, survival rates were 93%, 80%, 82%, 68%, and 40%, respectively. The difference between patients with combined scores of 5 or 6 was statistically significant (P = 0.02). CONCLUSIONS: Histologic grade of urothelial carcinoma based on the newly proposed WHO/ISUP grading system stratifies patients into prognostically significant groups. Grading should also take cancer heterogeneity into consideration, and prognostic accuracy appears to be increased when the combined primary and secondary grades are applied. [See editorial counterpoint on pages 1509-12 and reply to counterpoint on pages 1513-6, this issue.]

Predicting cancer progression in patients with stage T1 bladder carcinoma.

PURPOSE: A significant number of patients with stage T1 bladder carcinoma are at risk for cancer progression. We sought to identify factors associated with cancer progression in a series of patients with stage T1 bladder carcinoma treated with a contemporary therapeutic approach. PATIENTS AND METHODS: The study population consisted of 83 consecutive patients in whom stage T1 bladder carcinoma was diagnosed at the Mayo Clinic between 1987 and 1992. All patients underwent transurethral resection of the bladder (TURB) and had histologic confirmation of the diagnosis. The mean age was 71 years (range, 47 to 94 years). The male-to-female ratio was 3.9:1. The mean length of follow-up was 5.2 years (range, 1 day to 10.4 years). The depth of lamina propria invasion in the TURB specimens was measured with an ocular micrometer. Cancer progression was defined as the development of muscle-invasive or more advanced stage carcinoma, distant metastasis, or death from bladder cancer. RESULTS: The overall 5- and 7-year progression-free survival rates were 82% and 80%, respectively. The depth of invasion in the TURB specimens was associated with cancer progression (hazards ratio, 1.6 for doubling of depth of invasion; 95% confidence interval, 1.03 to 2.4; P =.037). The 5-year progression-free survival rate for patients with depth of invasion of >/= 1.5 mm was 67%, compared with 93% for those with depth of invasion of less than 1.5 mm (P =.009). No other variable, including age, sex, tobacco use, alcohol use, the presence of carcinoma-in-situ, histologic grade, lymphocytic infiltration, or muscularis mucosae invasion, was associated with cancer progression. CONCLUSION: The depth of invasion in the TURB specimens, measured with a micrometer, is predictive of cancer progression in patients with stage T1 bladder carcinoma.

Survival of patients with carcinoma in situ of the urinary bladder.

BACKGROUND: To the authors' knowledge, the long term follow-up of patients with carcinoma in situ of the urinary bladder is limited. METHODS: The authors studied 138 patients diagnosed with urothelial carcinoma in situ of the bladder at the Mayo Clinic between 1972-1979. All the histologic slides were reviewed and fulfilled the diagnostic criteria for carcinoma in situ according to the newly proposed World Health Organization and International Society of Urologic Pathology classification system. None of these patients had previous or coexisting invasive urothelial carcinoma at the time of diagnosis. Cox proportional hazards models were used to determine the prognostic significance of numerous clinical and pathologic findings using progression free, cancer specific, and all-cause survival as the endpoints for analysis. Progression was defined as the development of invasive carcinoma, distant metastases, or death from bladder carcinoma. RESULTS: The patients ages at the time of diagnosis ranged from 32-90 years (mean, 65.6 years). The male to female ratio was 7:1. Carcinoma in situ usually was multifocal (50%) with a predilection for the trigone, lateral wall, and dome. The mean follow-up after surgery was 11.0 years (range, 0.7-25 years). Actuarial progression free, cancer specific, and all-cause survival rates were 63%, 79%, and 55%, respectively, at 10 years, and 59%, 74%, and 40%, respectively, at 15 years. The mean interval from the time of diagnosis to cancer progression was 5 years. Patient age at diagnosis was significant in predicting progression free (P = 0.01) and all-cause survival (P = 0.002). Cystectomy performed within 3 months after the initial diagnosis was associated with improved all-cause survival (P = 0.03). After controlling for age, there was no difference in survival between patients who received immediate cystectomy and those did not (P = 0.16). CONCLUSIONS: Patients with carcinoma in situ of the bladder are at significant risk of cancer progression and death from bladder carcinoma. Cystectomy does not appear to offer a significant survival advantage in patients with carcinoma in situ of the bladder after adjusting for age.