Early stage ovarian cancer: the Italian contribution to clinical research.An update

Early ovarian cancer (stages IA-IIA) accounts for 30% of all epithelial ova rian cancer. Even if relatively uncommon, when "high risk" patients are con sidered, it is lethal in 25-30% of the cases. Mainstay of treatment is surg ery followed by either adjuvant chemotherapy or radiotherapy when indicated on the basis of still debatable prognostic factors. Literature data show a great variability in survival rate due to the great heterogeneity of patie nts considered in different reports and few randomized trials affected by a consequent low power. Italian groups have contributed both in investigatin g the role of surgery and of chemo or radiotherapy in the treatment of this disease. An important contribution in surgery has been made by Italian institutions in reducing the extent of surgery in young patients wishing to retain their reproductive capability showing that a "conservative surgery" (unilateral oophorectomy) can be safely performed in initial stages without affecting t he probability of cure. Another important surgical topic investigated by It alian institutions concerns the role of lymphadenectomy. In early ovarian c ancer the node involvement ranges between 14-24% in stage I and 37-50% in s tage II. Although the node positivity rate detectable by sampling (SA) is l ower than the one shown by a systematic procedure (LY), no data at the mome nt show that patients undergoing a sampling evaluation have a poorer progno sis. From 1992 through 1994, 202 patients (SA: 99; LY: 103) were enrolled b y six Italian institutions in a randomized trial aimed to assess the diagno stic and therapeutic role of SA vs. LY in early stage ovarian cancer. Posit ive nodes were detected in 9.9% vs. 19.3% respectively as well as a differe nt proportion of intra/perioperative complications occurred. No difference in time to relapse nor in overall survival were detected in the two groups showing no evidence of efficacy in favor of extensive staging of the retrop eritoneum. From 1983 to 1990, 271 stage I ovarian cancer patients entered two prospect ive multicentric randomized trials conducted by Italian institutions. Trial I compared cisplatin (50 mg/m(2), six cycles repeated every 28 days) vs. n o further treatment in stage IA-B grade 2-3 patients; Trial II compared the same dose and schedule of cisplatin vs. intraperitoneal P-32 in stage IC p atients. Cisplatin significantly reduced the relapse rate by 65% in Trial I and by 61% in Trial II, but survival was not affected (Trial I: HR = 1.15, 95% CI = 0.44-2.98; Trial II: HR = 0.72, 95% CI = 0.37-1.43). The final co nclusion drawn by these two important Italian studies was that adjuvant cis platin treatment in early ovarian cancer prevents relapse although the impa ct of chemotherapy remains unclear. For this reason two international trial s have been performed (ICON1 and ACTION) aimed at assessing the role of pla tinum-based chemotherapy on survival. Italian collaboration in both trials has been important, including about half of the total number of the 900 ran domized patients. Results will probably be available during this year and a re expected with a great interest by the whole scientific international com munity.