Association of Hospital Procedure Volume and Outcomes in Patients with Colon Cancer at High Risk for Recurrence

Context Evidence suggests that long-term survival is worst when patients have colorectal cancer surgery at hospitals that perform a small volume of these procedures. However, these studies have not examined cancer-specific outcomes. Contribution Among patients in a randomized trial of adjuvant chemotherapy, lower long-term survival at low-volume hospitals was not due to higher rates of colorectal cancer recurrence or cancer-specific death. Implications Poor long-term survival in hospitals with low rates of colorectal cancer surgery may be due to the poor general health of populations cared for at low-volume hospitals rather than to low-quality cancer surgery. The Editors Hospital procedure volume has been used as a proxy for institutional proficiency (1) and has been studied extensively as a predictor of clinical outcomes in complex medical and surgical procedures (1-15). Outcomes after less complex cancer surgeries, including operations for colon and breast cancer, also seem to be improved at high-volume centers (12, 13, 16, 17). Most of these studies have relied on administrative claims-based sources. Such studies, which rely on administrative data and even hybrid sources, such as the linkage of Medicare and the Surveillance, Epidemiology, and End Results (SEER) data, lack detailed information about patient and tumor characteristics. Moreover, because data on cancer relapse are often not available, it remains unclear whether the influence of lower hospital procedure volume on survival is directly related to a higher rate of cancer recurrence. A recent analysis of Medicare beneficiaries in the SEER registry found diminished long-term survival among patients who underwent colon cancer surgery at low-volume hospitals (13). This survival difference persisted after adjustment for perioperative mortality and the use of postoperative adjuvant chemotherapy. The authors concluded that, after adjustment for other factors, colon cancer surgery at high-volume hospitals improves colon cancer outcomes, possibly because of greater oncologic surgical expertise at high-volume surgical hospitals. However, because complete data on cancer recurrence were not available in the SEERMedicare database, this study could not address whether hospital procedure volume predicted any differences in colon cancer recurrence. Consequently, the underlying mechanism for the observed volumeoutcome relation in colon cancer remained uncertain. We therefore used data from a large randomized trial of patients with stage II and stage III colon cancer to examine the influence of hospital procedure volume on long-term outcome. Because patients were identified for this trial 4 to 6 weeks after colon cancer surgery, surgery was performed before study enrollment at various hospitals that had a wide range of surgical volume. Since all patients in this trial received standard postoperative adjuvant chemotherapy and follow-up, we could isolate the influence of hospital surgical volume beyond other potential confounding variables. Finally, because data on cancer recurrence and cancer-specific survival were available for all patients, we examined any differences in cancer recurrence rates across hospital surgical volume. Methods Study Sample Patients for this analysis were drawn from the National Cancer Institutesponsored Intergroup 0089 (INT-0089) randomized trial of adjuvant chemotherapy for stage II and stage III colon cancer, which was conducted between August 1988 and July 1992 (18, 19). The study had a nationwide enrollment of 3759 patients, with participation by institutions affiliated with 1 of the following cooperative groups: Eastern Cooperative Oncology Group (ECOG; the coordinating group), Southwest Oncology Group (SWOG), and Cancer and Leukemia Group B (CALGB). Eligible patients had histologically proven adenocarcinoma of the colon that had been resected en bloc without evidence of residual gross or microscopic disease. The inferior margin of the primary tumor must have been above the peritoneal reflection. Patients were eligible if there was evidence of spread of tumor to regional lymph nodes (Dukes C or tumor, node, metastasis [TNM] classification system stage III tumor). In addition, patients with penetration of the tumor into or through the bowel serosa without regional lymph node spread (Dukes B2 or TNM stage II) were eligible if there was evidence of bowel obstruction, bowel perforation, peritoneal implants, or adherence to or invasion of adjacent organs by the primary tumor. All patients were required to give written informed consent and were randomly assigned between 21 and 35 days after surgery. Patients must have had an ECOG performance status of 2 or less (ambulatory for at least 50% of the day or better) (20). Patients were also required to have adequate bone marrow, renal, and hepatic function (leukocyte count 3.5 109 cells/L; platelet count 100 109 cells/L; serum creatinine level 3 times the upper limit of normal; and bilirubin, aspartate aminotransferase, and alkaline phosphatase levels 3 times the upper limit of normal). Pregnant or lactating women were not eligible for enrollment. In addition, patients with a concurrent malignant disease or any malignant tumor within the previous 3 years (except for superficial squamous- or basal-cell carcinoma of the skin or in situ carcinoma of the cervix) were ineligible. Patients receiving any concurrent radiation or chemotherapy, previous radiation or chemotherapy for the cancer present at enrollment, or previous exposure to 5-fluorouracil were also not eligible for entry into this trial. All participating centers were required to obtain institutional review board approval before the start of the trial. The treatment groups for the trial have been previously described (18, 19, 21, 22). For our analysis, study staff, who were blinded to patient outcome, reviewed the operative reports of all eligible patients (198 patients in the treatment trial were ineligible and excluded from this cohort; reasons for exclusion have been previously described [21]) to identify the hospital where primary colon cancer surgery was performed. We also excluded patients who were missing sufficient information to identify the hospital of surgery (n = 51). In addition, because hospital procedure volume rankings were derived from U.S. Medicare claims, we excluded patients who underwent surgery at a Veterans Administration or military hospital (n = 303) or a hospital outside of the United States (n = 46). After these exclusions, 3161 patients were eligible for the analysis. Medicare Hospital Procedure Volume Using the U.S. Medicare claims database, we ranked hospitals by volume according to the number of primary colon cancer surgeries performed on all Medicare-enrolled patients between 1988 and 1993, the enrollment period inclusive of the clinical trial (13). Primary colon cancer surgeries were defined by using an International Classification of Diseases, 9th revision (ICD-9), diagnosis code of 153.x (colon cancer) or 154.x (rectal cancer) and an ICD-9 procedure code of either 45.7x or 45.8x (colon surgeries), or 48.4x, 48.5x, or 48.7x (rectal surgeries) for a particular hospitalization. Our results did not change when we used hospital volume rankings according to only colon cancer surgery (ICD-9 diagnosis code of 153.x and ICD-9 procedure code of either 45.7x or 45.8x), as the 2 rankings were highly correlated (r = 0.99). Validation of Medicare Procedure Volume In previous studies, Medicare case volume was highly correlated with total hospital procedure volume (2). To validate our Medicare procedure volume rankings for colorectal cancer surgery, we used the Nationwide Inpatient Sample (NIS) database from 1988 to 1992. The NIS database consists of a random sample of 750 to 900 hospitals per year from 11 states, approximating a 20% sample of U.S. community hospitals. Using the NIS database, we identified the total number of colorectal cancer surgeries performed using the same ICD-9 diagnostic and procedure codes, as described earlier, and created a parallel annual volume ranking for all hospitals that were represented in our cohort. Among hospitals that were jointly represented in our cohort study and the NIS database (255 hospitals), the Spearman rank correlation coefficient for annual colorectal cancer surgery volume, as measured by the Medicare claims database and the NIS database, was 0.92 (P < 0.001). This high correlation supports the use of procedure volume for colorectal surgery, as calculated from the Medicare claims database, as a valid measure of relative overall hospital procedure volume. Follow-up Patients were followed at least every 3 months from time of study entry for 1 year (for year-long treatment groups, more frequent provider visits and evaluations were required), then every 6 months for 5 years, and then annually until death. Because 95% of colon cancer recurrences occur within 5 years after surgery, data for treatment outcomes and therapeutic efficacy from INT-0089 have reached maturity as of the time of this analysis. The median follow-up time for patients included in this report is 9.4 years. Statistical Analysis The distribution of baseline characteristics across hospital procedure volume tertiles was evaluated by using chi-square tests for categorical variables and Wilcoxon rank-sum tests for continuous variables. Overall and recurrence-free survival rates were examined by using the KaplanMeier method (23), and differences among tertiles were assessed by using the log-rank test. Overall survival was defined as time from study entry to death from any cause. Recurrence-free survival was defined as time from study entry to tumor recurrence or occurrence of a new primary tumor. In recurrence-free survival analyses, patients who died without known tumor recurrence were censored at the last documented evaluation by the treating provider. Cancer-specific survival was defined as time from study entry