Does endogenous immune response determine the outcome of surgical therapy for metastatic melanoma?

Background: Although the presence of tumor cells in the blood of patients w ith metastatic melanoma suggests widely disseminated disease, many of these patients enjoy prolonged survival or cure after surgical resection. Our pr evious study of adjuvant vaccine therapy after complete resection of metast atic melanoma revealed a strong correlation between postoperative survival and elevated antibody titers to a 90-kDa tumor-associated antigen (TA90) ex pressed by melanoma cells of the vaccine. We hypothesized a similar correla tion between postoperative survival and endogenous anti-TA90 antibody titer s induced by the patient's melanoma in the absence of postoperative adjuvan t immunotherapy. Methods: From 1970 to 1996, 64 patients underwent complete resection of dis tant melanoma metastases and did not receive postoperative adjuvant immunot herapy. Serum collected within 4 months after surgery was tested in a coded and blinded fashion for anti-TA90 IgG and IgM by enzyme-linked immunosorbe nt assay, and for total IgG and IgM (controls) by radial immunodiffusion. Results: Median follow-up for the study population was 19 months (range, 3- 147 months). There was no significant correlation between anti-TA90 IgG tit er and total IgG level (P = .4785), or between anti-TA90 IgM and total IgM (P = .0989). Univariate analysis showed that postoperative anti-TA90 IgM ti ter as a continuous variable was significantly associated with overall surv ival (OS); i.e., the higher the anti-TA90 IgM titer, the longer the OS, Usi ng an established cutoff liter of 800, median OS was 42 months for patients with high anti-TA90 IgM titers (n = 28) vs. 9 months for patients with low titers (n = 36) (P = .0001). There was no significant correlation between total IgG/IgM and survival (P = .4107 and .4044, respectively). Multivariat e analysis identified anti-TA90 IgM as the most significant independent var iable influencing OS after complete resection of distant melanoma metastase s (P = .0001). Conclusions: We conclude that the endogenous immune response to metastatic melanoma determines the outcome after surgical therapy. Enhancement of this specific immune response may prolong the survival of patients with distant melanoma metastases.