Journal Club - February 2005

The second-look operation improves survival in suboptimally debulked stage III ovarian cancer patients.
Rahaman J, Dottino P, Jennings TS, Holland J, Cohen CJ.
Int J Gynecol Cancer. 2005 Jan/Feb;15(1):19-25. [Abstract]

Summary
Rahaman and coworkers conducted a single-institution retrospective cohort study between 1985 and 1994 of 175 women with stage III ovarian cancer eligible for second-look surgery based on a complete clinical response to primary treatment. During the study interval, a total of 230 women were treated for stage III ovarian cancer. Of the eligible patients (n=175), 109 actually underwent second-look surgery. For all 230 patients, the median follow-up time was 68.3 months and the 5-year survival rate was 43.4%. The authors performed mutiple survival comparisons of patient subgroups and noted no difference in 5-year survival rates between all patients undergoing second-look surgery (57.3%) and all patients not undergoing second-look surgery (48.7%, p=0.67). Comparing patients who had optimal primary cytoreductive surgery (residual disease „T1cm), there was again no difference in 5-year survival time according to second-look surgery (69% for second-look, 61% for no second-look, p=0.7). However, when patients left with suboptimal residual disease at primary surgery (n=47) were compared according to second-look status, those patients that were submitted to were found to have a statistically significant advantage in 5-year survival time (36%) compared to patients not undergoing second-look surgery (13%, p<0.05). Among the subgroup of patients with suboptimal initial surgery, multivariate survival analysis was performed to control for confounding variables and revealed that second-look status was the only independent clinical variable that affected subsequent survival outcome.

Discussion
Second-look surgery for ovarian cancer has received a significant amount of criticism in recent years. Critics argue that no study to date has shown a survival advantage associated with such surgery, and the paper by Rahaman and coworkers indeed supports this observation. One must bear in mind, however, that second-look surgery was not initially incorporated into the management program of ovarian cancer patients as a therapeutic tool, but rather as a diagnostic tool to identify occult persistent disease after primary therapy. Despite recent advances in computed tomographic and positron emission tomography imaging techniques and serological tumor markers, second-look surgery remains the most sensitive diagnostic test to identify persistent ovarian cancer. The identification of persistent disease after completing primary therapy is important in several respects. First, it provides the patient with critical prognostic information ¡V that her disease is unlikely to be cured ¡V and allows for a more informed process of planning life events and self-determination. Secondly, proponents of second-look surgery argue, a positive result allows an opportunity for secondary tumor debulking and the early institution of salvage (second-line) therapy. While it has been difficult to correlate early institution of salvage therapy with prolonged survival, previous work by investigators at the Mayo Clinic (Podratz et al Am J Obstet Gynecol 1985; 152: 230) has shown that successful debulking at second-look surgery is associated with a survival advantage. The study by Rahaman et al is important in that it identifies a specific subgroup of patients (suboptimal primary surgery) that may indeed derive a survival benefit from second-look surgery. Unfortunately, in this study the authors did not analyze the amount of persistent disease identified at second-look and any effect of secondary debulking surgery. Presumably, this would have been associated with a positive survival outcome.

Conclusion
These data suggest that while second-look surgery should not be considered a therapeutic intervention for all patients with ovarian cancer, there is a specific subset of patients, those with suboptimal initial surgery, that may experience prolonged survival if successful debulking surgery can be undertaken at that time. While no survival advantage could be demonstrated for second-look surgery in the whole, it remains the most sensitive technique currently available for identifying persistent disease after primary therapy.

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