Systemic Therapy for Non-Serous Ovarian Carcinoma

Yanin Chávarri-Guerra; Eduardo González-Ochoa; Héctor De-la-Mora-Molina; Enrique Soto-Perez-de-Celis

Disclosures

Chin Clin Oncol. 2020;9(4):52 

In This Article

Malignant Ovarian Germ Cell Tumors (MOGCT)

MOGCT originate from primordial germ cells and sex cord-stromal derivatives, and include dysgerminomas, immature teratomas, embryonal tumors, non-gestational choriocarcinomas, and endodermal sinus (yolk sac) tumors.[2] MOGCT account for 3–5% of all ovarian malignant neoplasms, and are more often seen in young women and adolescent girls.[71]

Unlike EOC, MOGCTs usually present with abdominal symptoms including pain, a palpable pelvic mass, and/or ascites due to capsular distension, hemorrhage, and necrosis.[72] Although symptoms contribute to an earlier diagnosis, the majority of them are unilateral and diagnosed in stage I or II. The recommended initial workup includes serum tumor markers [alpha-fetoprotein (AFP), beta-human chorionic gonadotrophin (B-HGC)], chest X-ray, abdominal computed tomography and pelvic ultrasound.[72] B-HGC is elevated in patients with choriocarcinoma; AFP is found with tumors containing yolk sac tumor elements; embryonal carcinoma may produce both serum markers; and dysgerminomas produce low levels of B-HGC and lactic dehydrogenase (LDH). Serum markers play an important role in the diagnosis of MOGCTs and are considered of prognostic value and useful in the management and follow-up of patients, indicating remission or relapse. Other poor prognostic factors include advanced stage, histologic subtype (non-dysgerminoma/immature teratoma), and residual disease.[73] The most frequent histology is dysgerminoma, while non-gestational choriocarcinoma and embryonal carcinoma are less common.

MOGCTs have an excellent prognosis after multimodal therapy with surgery and adjuvant systemic treatment which is considered standard of care for these tumors (Table 3). The type of surgery depends on the tumor extension and traditionally fertility sparing surgery is considered acceptable.[74,75] It includes unilateral salpingo-oophorectomy, peritoneal washing, careful and systematic abdominal exploration with multiple biopsies of the pelvic and abdominal peritoneum, omentectomy, and retroperitoneal lymphadenectomy, including the bilateral pelvic and para-aortic lymph node areas. Total hysterectomy and bilateral salpingo-oophorectomy is reserved for those with more advanced disease.[76]

Combination chemotherapy has dramatically changed the prognosis of patients with MOGCTs. Vincristine, dactinomycin and cyclophosphamide was the standard of care in the early 1970's. Vinblastine, bleomycin and cisplatin (PVB) was also considered another effective regimen before bleomycin, etoposide and cisplatin (BEP) became the new standard in 1990.[77] BEP was compared with the PVB regimen in patients with germ cell testicular cancer, showing similar efficacy with significantly less toxicity, which led to its adoption for the treatment of women with MOGCTs.

Adjuvant chemotherapy is recommended for all patients with stage II to IV malignant dysgerminomas or immature teratomas; stage I, grade 2 to 3 immature teratomas; and any stage embryonal tumors or endodermal sinus tumors.[29] Only selected patients with stage IA or IB are candidates for observation. Four cycles of BEP is considered as the standard regimen, although some patients with low-risk or stage I disease may be treated with three cycles of BEP or three cycles of etoposide/carboplatin, particularly when avoidance of toxicity is critical.[77]

Another active regimen is POMB-ACE (cisplatin, oncovin-vincristine, methotrexate, bleomycin, actinomycin-D, cyclophosphamide, etoposide), which was initially used for patients with testicular cancer. It has shown similar RR compared to other regimens and is generally well tolerated.[78] Although MOGCTs have a favorable prognosis, recurrences can occur in a small percentage of cases. Due to the rarity of these tumors, treatment for recurrent disease is usually extrapolated from protocols developed for testicular cancer.[72]

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