Second primary malignancies following the treatment of early stage ovariancancer: Update of a study by the National Cancer Institute of Canada-Clinical Trials Group (NCIC-CTG)

Background: Ovarian cancer is the leading cause of death from gynecological malignancies and the fourth most frequent fatal malignancy in women. Despi te improved surgical techniques as many as 20% of women with early stage di sease will eventually relapse and die from their disease. The post-operativ e management of these women remains controversial. Here we present the long term follow-up data of our previously published study, as well as the inci dence of second primary malignancies in these women. Patients and methods: Two hundred fifty-seven eligible patients with stage I, IIA `high risk' ovarian carcinoma and IIB, IIIO (disease confined to pel vis) were randomized to either whole abdominal radiotherapy 2,250 rads in t en fractions (107 patients), melphalan 8 mg/m(2)/d x 4 weeks x 18 courses ( 106 patients) or intraperitoneal chromic phosphate 10-20 mCi (44 patients). All patients were initially treated with pelvic radiotherapy. Results: Overall survival estimates at 10 years were: 45% in the whole abdo minal radiotherapy arm; 49% in the melphalan arm and 50% in the intraperito neal chromic phosphate arm (P = 0.30). Relapse-free survival estimates at 1 0 years were: 50% in the whole abdominal radiotherapy arm, 62% in the melph alan arm and 51% in the chromic phosphate arm (P = 0.147). Long term follow -up has not demonstrated a significant difference between treatment arms. S econd primary malignancies developed in 29 women (11%) after 2,229 person y ears of follow-up. This compares to 18.7 second primary malignancies which would have been expected in this group of age-matched controls and was stat istically significant (P = 0.018). There was no significant difference in t he total number of second primary malignancies between treatment arms. Melp halan appeared to be associated with an increased risk of developing leukem ia/myelodysplastic syndrome compared to the whole abdominal radiotherapy ar m (P = 0.06). Conclusions: Long-term follow-up has not demonstrated a significant differe nce in overall or disease free survival between treatment arms. An excess o f second primary malignancies (35%) was observed suggesting that lifelong s urveillance is required in this population. Further research with newer tre atment programs are needed to improve the cure rates in this population.