Preoperative chemotherapy is as effective as postoperative chemotherapy, permits more lumpectomies, is appropriate for the treatment of certain patients with stages I and II disease, and can be used to study breast cancer biology. Tumor response to preoperative chemotherapy correlates with outcome and could be a surrogate for evaluating the effect of chemotherapy on micrometastases; however, knowledge of such a response provided little prognostic information beyond that which resulted from postoperative therapy.

Preoperative therapy reduced the size of most breast tumors and decreased the incidence of positive nodes. The greatest increase in lumpectomy after preoperative therapy occurred in women with tumors > or = 5 cm, since women with tumors less than 5 cm were already lumpectomy candidates. Preoperative therapy should be considered for the initial management of breast tumors judged too large for lumpectomy.

The current findings completely affirm the validity of our original observations indicating the appropriateness of grouping primary breast cancer patients into those with negative, 1 to 3, or ≫4 positive nodes. Results, however, reveal that there is a risk in combining all patients with ≫4 positive nodes into a single group. Since there was a 25% greater disease‐free survival and an 18% greater survival in those with 4 to 6 than in those with ≫13 positive axillary nodes, such a unification may provide misleading information regarding patient prognosis, as well as the worth of a therapeutic regimen when compared with another from a putatively similar patient population. Of particular interest were findings relating the conditional probability, i.e., the hazard rate, of a treatment failure or death each year during the 5‐year period following operation to nodal involvement with tumor. Whereas the hazard rate for those with negative, or 1 to 3 positive nodes, was relatively low and constant, in those with ≫4 positive nodes the risk in the early years was much greater, but by the fifth year it was similar to that occurring when 1‐3 nodes were involved, and not much different from negative node patients. The same pattern existed whether 4 to 6 or ≫13 nodes were positive. When the current findings are considered relative to other factors with predictive import, it is concluded that nodal status still remains the primary prognostic discriminant.

Information is presented from 555 patients with Dukes B and C rectal cancers treated by curative resection who were entered into the National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol R-01 between November 1977 and October 1986. Their average time on study was 64.1 months. The patients were randomized to receive no further treatment (184 patients), postoperative adjuvant chemotherapy with 5-fluorouracil, semustine, and vincristine (MOF) (187 patients), or postoperative radiation therapy (184 patients). The chemotherapy group, when compared with the group treated by surgery alone, demonstrated an overall improvement in disease-free survival (P = .006) and in survival (P = .05). Employing the proportional hazards model, a global test was used to determine the presence of treatment interactions. Investigation of stratification variables employed in this study indicated that sex, and to a lesser extent age and Dukes stage, made individual contributions to the disease-free survival and the survival benefit from chemotherapy. When evaluated according to sex, the benefit for chemotherapy at 5 years, both in disease-free survival (29% vs. 47%; P less than .001; relative odds, 2.00) and in survival (37% vs. 60%; P = .001; relative odds, 1.93), was restricted to males. When males were tested for age trend with the use of a logistic regression analysis, chemotherapy was found to be more advantageous in younger patients. When the group receiving post-operative radiation (4,600-4,700 rad in 26-27 fractions; 5,100-5,300 rad maximum at the perineum) was compared to the group treated only by surgery, there was an overall reduction in local-regional recurrence from 25% to 16% (P = .06). No significant benefit in overall disease-free survival (P = .4) or survival (P = .7) from the use of radiation has been demonstrated. The global test for interaction to identify heterogeneity of response to radiation within subsets of patients was not significant. In conclusion, this investigation has demonstrated a benefit from adjuvant chemotherapy (MOF) for the management of rectal cancer. The observed advantage was restricted to males. Postoperative radiation therapy reduced the incidence of local-regional recurrence, but it failed to affect overall disease-free survival and survival.

The addition of postoperative radiation therapy to chemotherapy in Dukes' B and C rectal cancer did not alter the subsequent incidence of distant disease, although there was a reduction in locoregional relapse when compared with chemotherapy alone.

Four hundred patients with resectable colon and rectal cancers were operated on by 37 surgeons at 31 institutions. Patients were monitored with carcinoembryonic antigen (CEA) level determinations and clinical examinations. One hundred thirty patients had recurrences, and 75 were reoperated on, with 43 reoperations CEA‐directed and 32 clinically directed. Two of 75 died within 1 month after the second operation. Twenty‐two second‐look patients remain free of disease 5 years after their second operaton. The highest resectability of recurrent cancer occurred in patients with a CEA level below 11 ng/ml in whom the CEA level was determined at intervals of 1 to 2 months. Cancer 55:1284‐1290, 1985.

The present study examines the prognostic significance of tumor location and bowel obstruction in Dukes B and C colorectal cancer. Data were obtained from 1021 patients entered into two randomized prospective clinical trials of the NSABP. Tumor location proved to be a strong prognostic discriminant. Lesions located in the left colon demonstrated the most favorable prognosis. Tumors of the rectosigmoid and rectum had the worst prognosis with the relative risk of treatment failure for the latter being over three fold that of the left colon. When the relative risks associated with tumor location were adjusted for nodal imbalances, the left colon continued to demonstrate the most favorable prognosis. The presence of bowel obstruction also strongly influenced the prognostic outcome. Examination of the data without considering tumor location disclosed that patients with bowel obstruction were at greater risk for treatment failure than those without obstruction. The effect of bowel obstruction was influenced by the location of the tumor. The occurrence of bowel obstruction in the right colon was associated with a significantly diminished disease-free survival, whereas obstruction in the left colon demonstrated no such effect. This phenomenon was independent of nodal status and tumor encirclement, the latter two factors proving to be of prognostic significance independent of tumor obstruction. A multivariate analysis in which the covariate effects of sex, age, nodal status, tumor obstruction, encirclement, and tumor location were adjusted underscored the role of tumor location and obstruction as prognostic discriminants. The results indicate that the definition of prognostic factors can identify patient subsets with unique characteristics.

In 1971, the National Surgical Adjuvant Breast Project (NSABP) implemented a prospective randomized clinical trial to compare the worth of alternative treatments with radical mastectomy in women with primary operable breast cancer. Information has been obtained from 1,665 patients eligible for follow-up from 34 NSABP member institutions in Canada and the United States. Results from that trial, at present in its sixth year with patients on study for an average of 36 months, (26 to 62 months), fail to demonstrate an advantage for those who had a radical mastectomy. No significant difference in the treatment failure or survival has as yet been observed in clinically negative node patients who have been randomly managed by conventional radical mastectomy, total mastectomy with postoperative regional radiation or total mastectomy followed by axillary dissection of those patients who subsequently develop positive nodes. Similarly, there presently exists no difference between patients with clinically positive nodes treated by radical mastectomy o r by total mastectomy followed by radiation. Of particular interest is the observation that based upon findings from radical mastectomy patients, there may be as many as 40% of patients having a total mastectomy who had histologically positive nodes unremoved, to date only 15% have developed positive nodes requiring a n axillary dissection. The persistence of such a difference in incidence would have profound biological significance. The discovery that leaving behind positive axillary nodes has as yet not been influential in enhancing the incidence of distant metastases o r the overall proportion of treatment failures and that a disproportionate number of treatment failures in the total mastectomy group occurred in those patients who subsequently required axillary dissection provides reinforcement to the view that positive axillary lymph nodes are not the predecessor of distant tumor spread but are a manifestation of disseminated disease.comer 39:2827-2839,1977. HERE HAS EXISTED GREAT CONTROVERSYtional Surgical Adjuvant Breast Project T concerning the treatment of primary breast (NSABP), after almost a decade of planning cancer. Prompted by that uncertainty, the Na-initiated in August of 1971, a prospective ran-