Surgery versus radiochemotherapy for resectable locally invasive pancreatic cancer: final results of a randomized multi-institutional trial.

PURPOSE: Although the outcome of surgery for locally advanced pancreatic cancer remains poor, it is improving, with 5-year survival up to about 10% in Japan. The preliminary results of our multi-institutional randomized controlled trial revealed better survival after surgery than after radiochemotherapy. We report the final results of this study after 5 years of follow-up. METHODS: Patients with preoperative findings of pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric or common hepatic arteries, or distant metastasis, were included in this randomized controlled trial, with their consent. If the laparotomy findings were consistent with these criteria, the patient was randomized to a surgery group or a radiochemotherapy group (5-fluorouracil 200 mg/m2/day and 5040 Gy radiotherapy). We compared the mean survival time, 3-and 5-year survival rates, and hazard ratio. RESULTS: The surgery and radiochemotherapy groups comprised 20 and 22 patients, respectively. Patients were followed up for 5 years or longer, or until an event occurred to preclude this. The surgery group had significantly better survival than the radiochemotherapy group (P<0.03). Surgery increased the survival time and 3-year survival rate by an average of 11.8 months and 20%, respectively, and it halved the instantaneous mortality (hazard) rate. CONCLUSION: Locally invasive pancreatic cancer without distant metastases or major arterial invasion is treated most effectively by surgical resection.

Long-term cure in surgery for extrarectal pelvic recurrence of rectal cancer.

PURPOSE: Survival benefit of radical surgery for locally recurrent rectal cancer depends on whether disease is cured rather than whether death is delayed. Cured patients gain decades of life and are spared from sufferings with recurrence. Unfortunately, the majority of patients undergoing surgery, particularly those with extrarectal pelvic recurrence, have poor outcomes with occult disseminated disease. This study was designed to identify which of these patients are curable. METHODS: Of 61 patients with pelvic recurrence treated by radical reexcision more than nine years before, 36 patients whose initial surgery was abdominoperineal resection were examined retrospectively. We used the logistic regression and Gamel-Boag regression models to estimate curability and identify predictors of cure. RESULTS: Ten patients survived five years and seven survived ten years. The cumulative disease-specific mortality curve leveled off 6.5 years after reexcision and remained at 74 percent (95 percent confidence interval, 60-89), indicating that the remaining 26 percent are curable. This value is comparable with the 23 percent curability estimated by the Gamel-Boag model, which also found that the disease-free interval from the initial surgery to the first recurrence is the best predictor of cure (P = 0.005). Of 11 patients with disease-free interval three years or more, 6 survived ten years, whereas 8 of 9 patients with disease-free interval less than one year died of second recurrence within three years of reexcision. CONCLUSIONS: Even patients with extrarectal pelvic recurrence may have isolated disease that is amenable to complete eradication. As a biologic marker, the disease-free interval serves to predict curability and may distinguish isolated disease from occult disseminated disease.

Evaluation of intensive adjuvant chemotherapy in gastric cancer using life expectancy compared with log-rank test as a measure of survival benefit.

BACKGROUND: The goal of radical cancer surgery with or without adjuvant therapy is to cure disease rather than to delay death. There is concern that the survival benefit of curative treatment may not be properly appreciated by the log-rank test (LRT), which is more sensitive to treatment that delays death than to treatment that achieves cure. To confirm this concern and to evaluate the survival benefit of adjuvant chemotherapy, the data from a previous randomized controlled trial are analyzed using both traditional and new methods. METHODS: In this trial, 1410 gastric cancer patients with serosal or subserosal invasion had been classified by nodal and serosal status into four strata and randomized to receive high-dose or low-dose adjuvant regimens (mitomycin and tegafur-uracil) after gastrectomy. The two treatment groups were compared using the LRT as well as the life expectancy (LE) derived from the Boag model and the competing risk model. RESULTS: The LRT showed no significant difference between the two groups, whereas the LE increased significantly with high-dose chemotherapy (1.4-year gain; 95% CI = 0.1-2.8). A greater gain of 4.4 years occurred exclusively in the serosa-negative node-positive stratum, associated with a 21% increase in cure rate. The gain in LE was particularly greater in younger patients. CONCLUSIONS: Parametric LE analysis offers more relevant information about curative treatment than LRT. It suggests that high-dose chemotherapy may achieve cure in a subset of patients, eradicating residual malignancies left behind after gastrectomy and providing greater survival benefit than expected from LRT.

A randomized multicenter trial comparing resection and radiochemotherapy for resectable locally invasive pancreatic cancer.

BACKGROUND: Though the outcome of resection for locally invasive pancreatic cancer is still poor, it has gradually improved in Japan, and the 5-year survival is now about 10%. However, the advantage of resection over radiochemotherapy has not yet been confirmed by a randomized trial. We conducted this study to compare surgical resection alone versus radiochemotherapy without resection for locally invasive pancreatic cancer using a multicenter randomized design. METHODS: Patients with pancreatic cancer who met our preoperative criteria for inclusion (pancreatic cancer invading the pancreatic capsule without involvement of the superior mesenteric artery or the common hepatic artery, or without distant metastasis) underwent laparotomy. Patients with operative findings consistent with our criteria were randomized into a radical resection group and a radiochemotherapy group (200 mg/m(2)/day of intravenous 5-fluorouracil and 5040 cGy of radiotherapy) without resection. The 2 groups were compared for mean survival, hazard ratio, 1-year survival, quality of life scores, and hematologic and blood chemical data. RESULTS: Twenty patients were assigned to the resection group and 22 to the radiochemotherapy group. There was 1 operative death. The surgical resection group had better results than the radiochemotherapy group as measured by 1-year survival (62% vs 32 %, P=.05), mean survival time (>17 vs 11 months, P < .03), and hazard ratio (0.46, P=.04). There were no differences in the quality of life score or laboratory data apart from increased diarrhea after surgical resection. CONCLUSIONS: Locally invasive pancreatic cancer without distant metastases and major arterial invasion appears to be best treated by surgical resection.

Parametric mean survival time analysis in gastric cancer patients.

BACKGROUND: The mean survival time (MS) has acquired increasing importance as an outcome indicator for patient care and technology assessment. The authors use lifelong follow-up data from gastric cancer patients to study whether the MS is predictable from 5-year follow-up information based on 2 parametric models. METHODS: The authors used 3597 gastric cancer patients operated on between 1950 and 1969 to create 50 groups. For each group, the disease-related survival curve (DRSC) was estimated from the 5-year follow-up data using the Boag model. The MS for the group was then estimated by combining the DRSC with the survival curve for the age and sex-matched contemporaries (control group) based on the competing risk model. Alternatively, it was estimated by using the DRSC and the MS for the control group (the survival limit model). These predicted MS values were compared with the full follow-up observations. RESULTS: Although individual prediction errors varied depending on the group size (63 to 3597 patients) and the length of MS (0.3 to 20.2 years), the mean prediction errors were reasonably small; the survival limit model overestimated MS by 4.7% (95% confidence interval [CI], 1.6 to 7.8) and the competing risk model by 3.2% (95% CI, 0.1 to 6.5). CONCLUSIONS: MS for gastric cancer patients is parametrically predictable from 5-year follow-up data. This analysis should be applicable to other diseases showing log-normal failure time distributions.