Long-Term vs. Short-Term Survival in Patients with Ovarian Cancer
ABSTRACT & COMMENTARY
Synopsis: Long-term survivors of ovarian cancer were more likely to have had optimal cytoreduction and a lower proliferation index, and less likely to express p53 than short-term survivors.
Source: Goff BA, et al. Obstet Gynecol 1998;92:88-93.
Goff and colleagues at the university of Washington reported on 23 women with stage III ovarian cancer who were observed for a median of 66 months, and compared them with 30 women who had median survival of 18 months. The goal of the study was to determine if oncogene overexpression in patients with advanced epithelial ovarian cancer correlates with survival. Using immunohistochemistry, tumors were immunostained for p53, HER-2/neu, and epidermal growth factor receptor (EGFR) and were evaluated quantitatively for expression of estrogen factor (ER), progesterone receptor (PR), and Ki-67, a marker of cellular proliferation. The two groups were similar in median age-52 vs. 55 years. Optimal cytoreduction was achieved in 11 of the 22 long-term survivors compared with seven of 30 short-term survivors, a significant difference (P = 0.05). The average level of Ki-67 expression was 43% in long-term survivors and 64% in short-term survivors (P = 0.007). Overexpression of p53 was seen in 54% of long-term survivors and 80% of short-term survivors (P = 0.05). A combination of Ki-67 level of 50% or greater plus p53 overexpression was seen in 22% of long-term survivors compared with 68% of short-term survivors (P = 0.005). EGFR, HER-2/neu, ER, and PR statuses did not differ significantly between the two groups.
COMMENT BY DAVID M. GERSHENSON, MD
Goff et al are pursuing a strategy that is also being studied by several other groups, including our own-identifying what is unique about long-term survivors of ovarian cancer compared with short-term survivors. The ultimate objective of such a study is to be able to prospectively segregate patients based on prognosis so that we may begin to individualize therapy. For those who are predicted to have a good prognosis, they can be treated with standard therapy. For those predicted to have a short survival, they may select to be treated with an aggressive investigational approach or, alternatively, to be treated with palliative therapy that provides optimal quality of life. Goff et al found that, of several molecular biomarkers, only p53 status and Ki-67 index correlated with survival. This concept is worth pursuing, and subsequent studies should build on what has been learned in this investigation. Larger studies with multivariate analysis will hopefully allow us to use biomarker profiles to predict outcome and to design better treatment approaches for our patients. Although our progress against advanced epithelial ovarian cancer has been incremental, we haven't witnessed any major breakthroughs. The key to success is to select molecular markers that reflect the biologic behavior of the tumor. Currently, this selection process is empirical and not totally hypothesis-driven. Standard practice in the United States does not include the routine determination of molecular markers to decide on optimal treatment, but this approach is not far away.
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