Epithelial ovarian cancer (EOC) always remains the most lethal gynecologic malignancy, guideline-recommended treatments for advanced ovarian cancer is primary debulking surgery followed by platinum-based chemotherapy. However, relapse would almost unavoidable. Conventional treatment for recurrent EOC is chemotherapy and/or cytoreduction. Other researches in ovarian cancer in progress include multiline or dose-dense chemotherapy and targeted agents such as PARP inhibitors, Anti-angiogenic agents, immunotherapies.
Dose-dense weekly paclitaxel scheme in epithelial ovarian cancer has obtained remarkable attention in the past decade. However, the efficacy of chemotherapy alone is limited. Chen, Wei-Chun et al.  analyze the response to dose-dense chemotherapy of weekly paclitaxel and 3-weekly carboplatin in sixteen patients with recurrent ovarian cancer, the median PFS of all patients were 10.9 months (range 4.3-40.5). The median disease-free survival (DFS) was 5.6 months (range 1.2-34.2).
Target therapy mainly including PARP inhibitors and anti-angiogenic agents which demonstrating efficacy with improved PFS and OS are mainly used as maintenance therapy for patients with recurrent ovarian cancer[3-6]. Meanwhile, Tumor burden is a potential marker of PARP inhibitor effects in ovarian cancer.
Immune therapy which targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) mechanism of tumor immune evasion is a promising field of ovarian cancer therapy. In recent years, these inhibitors are being investigated in clinical trials. Inconsistent results have been obtained between studies. Some reports demonstrate a survival benefit with increased PD-L1 tumor expression, while others have shown a negative result[8, 9].
For EOC, radiotherapy is not a routinely therapy. In recent years, studies have reported some favorable outcomes in patients with recurrent epithelial ovarian cancer treated with radiotherapy. Chang, JS et al. included patients with recurrent epithelial ovarian cancer eligible for involved-field radiation therapy (IFRT) either during diagnosis of the recurrence or after salvage therapies. The overall and complete response rates were 85.7% and 50%, respectively. After a median follow-up of 28 (range, 17-42) months, the median PFS was 7 months. The 2-year PFS rate was 39.3%. In the study of a multicenter, retrospective study (MITO RT-01), Macchia G et al. included 261 patients with metastatic, persistent, recurrent ovarian cancer (MPR-OC), carrying a total of 449 lesions treated by stereotactic body radiotherapy (SBRT). complete response (CR), partial response (PR) and stable disease (SD) to SBRT were observed in 291 (65.2%), 106 (23.8%), and 33 (7.4%) lesions.
The role of secondary cytoreductive surgery (SCS) in recurrent epithelial ovarian cancer is yet controversial. For platinum-sensitive recurrent ovarian cancer, SCS increases survival rate. In a case-control study，Marchetti, C et al.  included 46 platinum-sensitive recurrent EOC patients. 23 women undergone SCS and followed by platinum-based chemotherapy and olaparib maintenance. The other 23 women only received medical treatment. Median time to first subsequent therapy (TFST) was significantly longer in the SCS + medical group than in the medical group. Also, SCS + medical patients had better post-recurrence survival (PRS), with a 3-year PRS of 79% in SCS + medical group versus 42% in medical group. However, Coleman RL et al.  randomly assigned patients with recurrent ovarian cancer with platinum-sensitive in the Gynecologic Oncology Group (GOG)-213 trial, a phase 3 randomized prospective trial. The median OS was 50.6 months in patients with surgery and 64.7 months in patients without surgery (HR=1.29; 95% CI=0.97–1.72; p=0.08) while median PFS was 18.9 months in patients with surgery and 16.2 months in patients without surgery (HR=0.82; 95% CI=0.66–1.01). They concluded that secondary cytoreductive surgery followed by chemotherapy did not result in longer overall survival than chemotherapy alone.
The postoperative residual tumor mass is the most important prognostic factor. Indication to Secondary cytoreductive surgery should be individualized. Early diagnosis of recurrence is the key of the possibility of surgery and complete cytoreduction would improve the prognosis.
One advantage of our case is early diagnosis of recurrence. Regular follow-up and early diagnosis of recurrence is of great importance for EOC after primary therapy. If the recurrence is isolated, there maybe the chance of secondary cytoreductive surgery and relatively good prognosis. Unfortunately, cases with isolated recurrences are not common. Many cases have disseminated lesions at the time of diagnosis. The rigorous surveillance of patients after primary treatment is a challeng in clinical practice. We think the suspicion of recurrence should be considered once the serum CA125 levels elevated to more than 15U/ml or two times of its lowest level. In this case report, PET-CT discovered metastatic foci in early-stage even if the serum tumor marker remains in normal range. Highly alertness of recurrence in the follow-up of EOC patients is important. With the help of high-quality image, clinicians could correctly monitor patients, distinguish relapse patterns and preform correct management management.
Most of the recurrent lesions were near or adhered by even infiltrated surrounded important organs such as ureter, vagina, cyst, intestine or rectum. Sometimes tumors could not be removed because their removal would cause severe functional disability or life-threatening bleeding. Since reported by Brunschwig in 1948, the pelvic exenteration (PE) has become an important method to treat pelvic malignancies. However, such management has remained controversial because of its severe functional disability or heavy hemorrhage especially when the tumor fixed to the pelvic sidewall. New treatment strategies for unremovable lesion in secondary cytoreductive surgery for recurrent ovarian cancer are needed.
Another particularity and highlight of our case are partially tumor resection with salvage 125I seeds implantation which did not interfere with the function of the patient and received good effects.
Compared to the other kinds of radiotherapy, 125I brachytherapy has several advantages. Its benefit is boosted by natural increases in local dose. 125I seed local treatment can reduce the tumor burden, relieve local symptoms and improve quality of life of patients. Early in 1991, Iodine-125 interstitial implants as salvage therapy for recurrent gynecologic malignancies including one ovarian carcinoma has been reported. Now 125I brachytherapy has increasingly been used for other sites of disease, such as central nervous system, head and neck tumors, lung, hepatic and pancreatic cancer and so on. Efficacy and safety of iodine-125 radioactive seeds brachytherapy has been approved[17, 18].
In 1999, there has been American Brachytherapy Society (ABS) recommendations for the clinical quality assurance and guidelines of permanent prostate brachytherapy with 125I . In 2018, Chinses expert consensus statement on computed tomography-guided 125I radioactive seeds permanent interstitial brachytherapy has been developed .
In radiotherapy-naive patients with unresectable isolated recurrent gynecologic malignancies, 125I implants are feasible and may possibly contribute to survival. Unlikely as cervical carcinoma or endometrial carcinoma, radiotherapy is not usually been used primarily in patients with ovarian epithelium cancer. As a result, 125I brachytherapy is a hopeful therapy for recurrent ovarian cancer.
The success of 125I brachytherapy is dependent on and the size of tumors and the accurate placement of radioactive seeds. Usually, all the 125I seeds implantation was performed with CT or ultrasound guidance. In our case, 125I seed implanted directly under the vision of operation. On the one hand, tumor burden is reduced by surgery; on the other hand, 125I implantation is more accurate and safer. Combination of surgery and 125I seeds implantation improved the prognosis for recurrent epithelial ovarian cancer.