Abstract: We identified seven RCTs that enrolled 372 women. We could not pool results of trials as the treatment comparisons differed. Six RCTs (n = 340) conducted over 15 years ago, evaluated adjuvant therapy (chemotherapy, pelvic external irradiation or intra-peritoneal radioactive isotope therapy) after radical surgery; over 87% of participants had Stage I tumours. Most participants were followed up for over 10 years. Overall and recurrence-free survival were similar between both arms of these trials, except that one trial (n = 66) showed a significantly lower survival (P = 0.03) in women who received chemotherapy (thio-TEPA). Adverse effects of treatment were incompletely reported and all six trials were at high risk of bias. One further trial (n = 32) that recruited participants with bilateral serous tumours who were wishing fertility preservation, revealed a significantly increased chance of pregnancy (hazard ratio (HR) = 3.3, 95% CI 1.4 to 8.0) but non-significantly earlier disease recurrence (HR = 1.5, 95% CI 0.6 to 3.8) in the women who had ultra-conservative surgery (bilateral cystectomy) than in those who had conservative surgery (cystectomy and contralateral oophorectomy). This trial was at low risk of bias. Quality of life (QoL) was not documented in any included trial. We did not find any trials that compared radical with conservative surgery or laparoscopy with laparotomy. We did not find evidence to support the use of any specific type of adjuvant therapy for borderline ovarian tumours. RCTs evaluating the benefit of adjuvant therapy with optimally dosed chemotherapy and newer targeted drugs are necessary, particularly for advanced borderline ovarian tumours. The low mortality from borderline ovarian tumours should make recurrence-free survival, time to recurrence and morbidity important end points in such trials. Bilateral cystectomy may be offered to women with bilateral borderline ovarian tumours diagnosed intra-operatively who are wishing to preserve their fertility. Similarly, women who had RCTs comparing radical with conservative surgery and comparing laparoscopy with laparotomy are needed.

Plain-language summary: In this review, we found six trials which enrolled 340 patients who had undergone surgery for borderline ovarian tumours. These trials compared the number of deaths among women who had various forms of treatment or no additional treatment after surgery. In five of the trials, the women had tumours confined to the ovaries and most were followed up for over 10 years. Only one trial enrolled women with tumours that had spread beyond the ovary, and this trial followed patients up for less than three years, which is not long enough to detect any difference between groups receiving different treatments. None of the trials found any demonstrable benefit from any of the additional forms of treatment. However, all six trials were conducted over 15 years ago and since then platinum-based chemotherapy has become widely used to treat advanced ovarian cancer. However, only one of the trials in our review assessed this more modern type of chemotherapy. Further trials of platinum-based chemotherapy and of less toxic treatments are needed, looking at the benefit of reducing the anxiety and distress of further surgery and treatment for relapse. One further trial, which recruited 32 women who had borderline ovarian tumours in both ovaries, compared conservative surgery (taking away the most diseased ovary and removing the tumour from the other ovary) with ultra-conservative surgery (removing the tumours without taking away either ovary). Nearly all the women who had ultra-conservative surgery became pregnant compared with half of those who had conservative surgery. Although about two thirds of the women in the trial developed similar tumours again, most women got pregnant before the disease recurred, all had their recurrences treated by further surgery, none developed invasive ovarian cancer nor died of their tumour. This small study suggests that ultra-conservative surgery by an experienced surgeon with careful follow up for recurrence may be recommended for women with bilateral borderline ovarian tumours who still intend to have children but, ideally, this approach should be evaluated in other independent trials. Despite rigorous searches, we did not find any trial directly comparing conservative surgery with radical surgery (surgery to remove all of the female reproductive organs) or comparing keyhole surgery (laparoscopy) with open surgery (laparotomy) for women with borderline ovarian tumours. None of these trials looked at how the various treatments affected the quality of life (QoL) of the women.