By Yukio Sonoda, MD
Fall 2012 — Using optimal primary cytoreductive surgery followed by platinum- and paclitaxel-based chemotherapy to treat epithelial ovarian cancer can achieve a complete clinical response in approximately 80 to 90 percent of patients with early-stage disease and 50 percent of patients with advanced-stage disease. Despite these excellent response rates, only 10 to 15 percent of patients will obtain a sustained remission and the majority of patients will ultimately fall victim to their disease.
Although primary cytoreductive surgery is well accepted as the cornerstone of initial management, the use of cytoreductive surgery in the setting of recurrent disease is less clearly defined. Most of the available literature consists of nonrandomized studies that have shown conflicting results. Undoubtedly, patient selection played a significant role in the findings and conclusions of these studies. Currently, the Gynecologic Oncology Group is conducting a randomized study to define the benefit of secondary cytoreduction;(1) however, inherent selection biases may cloud the final conclusion. Since most patients with ovarian cancer will recur, the practicing clinician will undoubtedly be faced with a difficult task of determining which patients may benefit from a secondary cytoreductive surgery.
Researchers at Memorial Sloan-Kettering Cancer Center undertook the task of defining selection criteria for candidates for secondary cytoreduction.(2) The study population was composed of patients with recurrent epithelial ovarian carcinoma who had undergone primary surgery and platinum-based chemotherapy followed by a complete clinical remission of at least six months followed by a planned secondary cytoreductive surgery. The secondary cytoreduction was defined as a surgical exploration with the intent to resect all visible disease, and this surgery had to be performed at Memorial Hospital for patients to be included in the study. All patients who underwent secondary cytoreduction had a preoperative CT scan and were deemed by the surgeon to have recurrent disease amenable to resection.
For purposes of this study, carcinomatosis was defined as the presence of 20 or more tumor nodules noted at the time of surgery. Residual disease was documented as the largest diameter (cm) of the largest residual tumor nodule as determined by the operating physician at the end of the operation. Survival time was calculated as months from the secondary cytoreduction to death or date of last follow-up visit for those patients still alive.
One hundred and fifty-three patients were evaluated. On univariate analysis, patients with no gross and 0.1 to 0.5 cm residual disease were found to have significantly improved survival over those with larger residual disease. Using the cutoff point of 0.5 cm to differentiate “optimal” and “suboptimal” secondary cytoreduction, the median survival of patients optimally cytoreduced was 56 months compared with 27 months for those left with suboptimal disease.
Analyzing disease-free interval, it was noted that there was little change in survival for patients with a disease-free interval of six to 12 months. There was a significant change in survival for patients as the disease-free interval increased from 13 to 30 months. Then, after 30 months the survival benefit of prolonged disease-free interval plateaued. On multivariate analysis of analyzed prognostic factors, we found that disease-free interval, number of sites of recurrence, and residual disease after secondary cytoreduction had prognostic significance.
Median survivals were 30 months for a disease-free interval of six to 12 months, 39 months for a disease-free interval of 13 to 30 months, and 51 months for a disease-free interval longer than 30 months (P = 0.005). Median survivals were 60 months for single site of recurrence; 42 months for multiple sites but not carcinomatosis; and 28 months for carcinomatosis. Median survivals were 56 months for residual disease equal to or less than 0.5 cm after secondary debulking and 27 months for residual disease greater than 0.5 cm. In general, median survivals were significantly improved with longer disease-free intervals, fewer sites of recurrence, and secondary cytoreduction to 0.5 cm or less residual disease.
Although the management of recurrent ovarian cancer remains a dilemma, the data from this large series of patients seems to identify groups that may derive a survival benefit from secondary cytoreductive surgery [Table 1]. These data imply that the goal of secondary cytoreduction should be to achieve residual disease of < 0.5 cm, and in some instances, radical surgical techniques may be required to obtain this goal. We hope that physicians can use these selection criteria to offer patients with recurrent epithelial ovarian cancer a “second chance” at life.