Catherine Uzan

Long-term follow-up of patients with an isolated ovarian recurrence after conservative treatment of epithelial ovarian cancer: review of the results of an international multicenter study comprising 545 patients

OBJECTIVE To determine the long-term outcomes of patients with an isolated ovarian recurrence after fertility sparing surgery (FSS) for epithelial ovarian cancer (EOC) and to evaluate the recurrence rates (and location) according to the new 2014 International Federation of Gynecology and Obstetrics (FIGO) staging system. DESIGN Retrospective multicenter study. SETTING Teams having reported recurrence after FSS for EOC. PATIENT(S) Four series comprising 545 patients undergoing FSS and 63 (12%) recurrences. INTERVENTION(S) FSS (salpingo-oophorectomy for a majority of cases) for EOC. MAIN OUTCOMES MEASURE(S) Recurrences rates and characteristics of recurrent disease. RESULT(S) Among 63 recurrent patients, 24 (38%) recurrences were isolated on the spared ovary, and 39 (62%) arose at an extraovarian site. Among the patients with an isolated ovarian recurrence, three patients died after a median follow-up period of 186 months (range: 28-294 months). Among the patients with recurrent extraovarian disease, 24 died and 7 were alive with persistent disease after a median follow-up period of 34 months (range: 3-231 months). The overall rate of isolated ovarian and extrapelvic recurrences was higher for grade 3 tumors (compared with grades 1/2). CONCLUSION(S) The long-term survival of patients with an isolated ovarian recurrence after FSS for EOC remains favorable. The prognosis of patients with an extraovarian recurrence is poor compared with those who have an isolated recurrent ovarian tumor. Grade 3 tumors (compared to grades 1/2) give rise to a higher rate of extraovarian recurrences.

Fertility sparing treatment of recurrent stage I serous borderline ovarian tumours

Here we report the outcomes of 26 patients who relapsed following conservative surgical treatment of stage I serous borderline ovarian tumours treated initially with fertility-sparing surgery. All recurrences were diagnosed by systematic ultrasonography during follow-up. Eleven patients relapsed at least twice after such management. Twenty-one pregnancies were observed in 13 patients. Eleven of these patients became pregnant after the treatment of their first recurrence. All patients had a borderline ovarian tumour and/or non-invasive peritoneal implants at the time of the first recurrence but two of them had invasive ovarian and peritoneal disease at the time of the second or third recurrence (one of them died of disease). Fertility-preserving surgery remains a valuable alternative (if technically feasible), in young patients with recurrent SBOT, in the form of a non-invasive ovarian lesion, who wish to start a pregnancy. However, it should be associated with meticulous follow-up because the risk of progression to carcinoma exists, albeit small.

Adjuvant Chemotherapy in Stage I Ovarian Germ Cell Tumors: Should Indications and Treatment Modalities Be Different in Young Girls and Adults?

TO THE EDITOR: We were interested to see the excellent, recently published article by Billmire et al about the oncologic outcome of surveillance after initial surgery in 25 young girls who were treated for presumed low-risk ovarian germ cell tumors (OGCTs). This is a landmark article because it reports the results of a pediatric trial, and specific trials devoted to this topic are rare. The first key message of this article is that it confirms the feasibility of compressed bleomycin/etoposide/cisplatin (BEP) in pediatric OGCT. Adjuvant BEP is clearly the standard of care in adult OGCT. Despite reports regarding BEP in a pediatric population, many pediatricians remain reluctant to use this regimen in young patients because of the risk of secondary leukemias. Thus, there is no consensus about the modalities of adjuvant chemotherapy for OGCT in young girls. If we can agree that in stage I disease (stage IA according to the International Federation of Gynecology and Obstetrics staging system), chemotherapy can be deferred until relapse, the question is whether the efficacy of compressed BEP is compromised by the reduced dose of bleomycin (15 mg/m every 3 weeks v 30 mg once per week) and the delivery of etoposide and cisplatin over 3 versus 5 days. In the series of 25 patients treated by Billmire et al with low-risk OGCT, deferred compressed BEP was associated with one cancerrelated mortality. In our series of 52 adults with yolk sac tumors (YSTs) treated with adult BEP, none of the patients with stage IA disease died. If surgery alone is proposed for low-risk pediatric YSTs, the authors rightfully emphasize the critical importance of adherence to surgical guidelines (similar to our recommendations in adult OGCT) and careful monitoring. We have to add that there is an absolute necessity of systematic expert anatomopathologic review. Although patients presented in this series were enrolled onto a clinical trial, at least eight of 25 patients did not meet inclusion criteria for low-risk OGCT because of tumor rupture (n 3), no peritoneal cytology (n 1), immature teratoma with no focus of YST (n 1), or capsular invasion (n 3). We are concerned that in the real-life setting, there will be an even greater risk of stage underestimation that could compromise outcomes for patients who should really receive chemotherapy. This study provides useful information regarding the indications of adjuvant treatment, namely, the absolute necessity of chemotherapy in disease with a true stage of greater than I (Children’s Oncology Group classification). Among the seven patients in this series who, on careful review, had greater than stage I disease (capsule rupture in three patients, no peritoneal cytology in one patient, and capsular invasion in three patients), five patients experienced relapse. As stated by the authors, deferring chemotherapy for relapse was proposed to avoid the “potential morbidity of chemotherapy” in “50% to 60%” of patients. This approach has been previously reported. With this in mind, one key piece of information not reported in the article by Billmire et al is the toxicity of the BEP regimen in this pediatric population. In our experience with 52 adult patients with YSTs treated using BEP, there were no secondary malignancies with a median follow-up of 68 months. Therefore, if treatment-associated morbidity is low (as observed in adults), should we consider that adjuvant treatment may be appropriate in pediatric YSTs to avoid a rare but potentially lethal recurrence or a recurrence that is curable but has associated sequelae? Several groups consider that, given their higher rate of recurrence compared with other germ cell tumors (GCTs), all adult YSTs, whatever their stage I classification, require adjuvant treatment. The National Guidelines from the French Rare Ovarian Tumors Group recommend consideration of adjuvant BEP in stage IA YST. The last argument in favor of adjuvant chemotherapy concerns the potential impact on fertility in the case of recurrent disease. In the present series, five of 12 patients with recurrences had a recurrence that was localized to the pelvis. Surgical treatment of this recurrent disease could impair the potential postrecurrence fertility. Furthermore, one patient required second-line ifosfamide, paclitaxel, and carboplatin, with potential impact on final gonadal function. Our two questions about this major article are, first, what was the morbidity of the BEP regimen in this series, and second, did any patients require pelvic surgery for recurrence, and what was postrecurrence fertility among potentially fertile patients? Surgery alone and salvage chemotherapy are accepted as standard in stage I testicular GCTs. However, testicular studies have also demonstrated that bleomycin dose-intensity is critical. Therefore, we would argue that future studies investigating deferred chemotherapy in pediatric GCTs propose the most effective regimen, for example, adult BEP. Although the results reported by Billmire et al are interesting, this nonrandomized study with a small number of patients may not allow us to confidently alter the standard of care for stage I pediatric OGCTs (YSTs). However, this study has clearly opened the door for discussion.

Oncofertility Applied to Epithelial Ovarian Cancer

Conservative treatment, consisting in uterine preservation with unilateral salpingo-oophorectomy, can be proposed to selected patients with early epithelial ovarian cancer, with a desire for pregnancy after a histological review and surgical staging.

Tumeurs ovariennes associées à la grossesse : conduite diagnostique et thérapeutique

Avec la generalisation de l’echographie durant la grossesse, la decouverte d’une masse annexielle associee a une grossesse est une situation frequente. Le risque de malignite est tres faible. Il convient d’adopter une demarche diagnostique rigoureuse pour eviter les gestes inutiles ou a risque. Cependant, il ne faut pas meconnaitre une lesion suspecte et systematiquement reporter les explorations invasives au post partum. L’exploration chirurgicale peut etre necessaire et elle doit respecter un certain nombre de regles. Nous disposons de recommandations nationales pour la prise en charge de ces patientes, ce qui permet d’homogeneiser les pratiques pour leur offrir la meilleure prise en charge possible, dans une situation qui est le plus souvent stressante pour le couple et son medecin. La plupart du temps, la grossesse peut etre preservee. Il convient de limiter la prematurite induite. Les cas de ces patientes doivent etre declares dans le cadre du reseau nation (www.cancer-et-grossesse.fr).

Préservation de la fertilité dans les tumeurs borderline de l’ovaire et épithéliales malignes : place, modalités, résultats et limites

Ces dix dernieres annees ont vu beaucoup de travaux evaluant les resultats des traitements conservateurs dans les tumeurs ovariennes. Ce traitement conservateur est la chirurgie de reference chez les patientes ayant une tumeur borderline de l’ovaire (limitee et/ou avec implant[s] peritoneal non invasif). Chez les patientes presentant une tumeur epitheliale maligne de l’ovaire, cette chirurgie conservatrice d’un ovaire et de l’uterus ne peut etre envisagee que chez celles ayant une tumeur d’excellent pronostic (stade IA grade 1, voire grade 2, stade IC grade 1), ayant beneficie d’une chirurgie de stadification adequate et parfaitement suivies.