A 68-Year-Old Woman With Stage IV Ovarian Cancer

Ramez Eskander, MD: The case we’re discussing today is a case of a 68-year-old postmenopausal female, who initially presented with symptoms of abdominal bloating, early satiety, as well as fatigue and urinary frequency. These symptoms are vague in nature, but are relatively quite common in women who may be suffering from an underlying gynecologic malignancy. Her past medical history was notable for hypertension that was well controlled with single-agent lisinopril. With respect to her social history, she was retired, she had 3 grandchildren, she had no history of smoking, and also only used alcohol on social occasions.

Her physical examination was significant for abdominal distention, bloating, and a fluid wave, but really otherwise an unremarkable examination. Part of the examination, however, the pelvic examination, was significant for what appeared to be a mass that could be palpated in the pelvic cul-de-sac. And this prompted a pelvic ultrasound, which confirmed the presence of a right adnexal lesion. Given her postmenopausal status, her clinical symptoms, as well as a physical exam and ultrasound findings, a CT scan of the chest, abdomen, and pelvis was requested. The CT scan was notable for a complex right-sided pelvic mass, what appeared to be a pleural effusion, a potential intraparenchymal liver metastasis as well.

Based on the constellation of the above findings, both the physical exam as well as the CT imaging, an interventional radiology-guided biopsy was performed of a lymph node as well as the adnexal mass. The results of that biopsy were suggestive of a high-grade epithelial ovarian cancer. Her CA-125 [cancer antigen 125] was elevated at slightly over 400 U/mL, although she did have a preserved performance status, being able to carry out essentially all independent activities without limitation.

Based on the radiographic findings and in discussion with the patient, she was counseled about surgical intervention, and in this particular case, she was taken to the operating room for primary cytoreduction, with exploratory laparotomy, total abdominal hysterectomy, bilateral salpingo-oophorectomy, resection of pelvic lymph nodes, omentectomy, and surgical cytoreduction. However, and importantly, not all of the tumor could be removed at the time of the surgical procedure, and she did have residual disease greater than a centimeter in size that remained at completion of the surgical intervention. It’s important to bring this up because more and more we are using neoadjuvant chemotherapy approaches based on the CHORUS and the Vergote EORTC 55971 clinical trials, which showed similar outcomes with improved quality of life parameters. In such a situation, one could have also considered neoadjuvant chemotherapy rather than primary surgical resection, with the goal being a complete resection of all visible disease.

Following surgery, the patient was counseled regarding management options, and based on her disease, which was stage IVB in the context of the suspected intraparenchymal liver metastasis, she was started on chemotherapy with carboplatin/paclitaxel in combination with the antiangiogenic agent bevacizumab. She received 3 cycles of therapy, and then subsequently went on to have a secondary surgical exploration, where any residual or remaining tumor was successfully removed, and she had no visible residual disease at the end of the operative intervention. She then continued on her combination regimen, followed by maintenance single-agent bevacizumab.

At completion of the primary cytotoxic combination regimen with bevacizumab, the patient did have what appeared to be a radiographic response, and her CA-125, which again started at greater than 400 U/mL, had gone down to 40 U/mL. At her 3-month follow-up visit, she appeared to be in clinical and radiographic remission. Her physical examination was unremarkable, CT scan of the chest, abdomen, and pelvis were without evidence of disease recurrence, and her CA-125 had normalized at 18 U/mL.

This case is typical for a patient with advanced-stage ovarian cancer. Importantly, she presented with vague symptoms, abdominal bloating, potentially early satiety, fatigue. Sometimes it’s very difficult to pinpoint the etiology of these symptoms in the context of patient’s age and potential comorbidities. Nonetheless, the symptoms that she presented with are likely reflective of the intraperitoneal disease distribution that was seen on radiographic imaging in the form of CT scan, which was appropriately ordered.

This patient, based on radiographic imaging, appeared to have stage IVB disease. There was an intraparenchymal liver lesion, the patient also appeared to have a malignant pleural effusion, meaning that she had advanced-stage disease that’s going to require aggressive intervention, multimodal therapy. We know that patients with stage IVB disease can be put into remission with a combination of chemotherapy and surgical resection. Again, most commonly for patients such as this, the approach is neoadjuvant chemotherapy followed by interval surgical cytoreduction, and then additional postoperative adjuvant chemotherapy. Importantly, despite the fact that we can put the majority of these patients into remission, we understand that the recurrence rate is quite high, likely on the order of 75% to 80%, and some would argue even higher. So our initial therapies may be successful at achieving remission, but we will be challenged with disease recurrence, and that really drives our desire to develop novel treatment strategies for such patients.

More recently, tumor mutational burden status has emerged as an area of interest. In early April of 2020, the FDA granted priority review for pembrolizumab in tumor mutational burden-high malignances, and there may be an opportunity here, even in the ovarian cancer space, to capitalize on this disease site–agnostic approval.

Transcript edited for clarity.

Case Overview:

Initial Presentation

• A 68-year-old postmenopausal woman presented with fatigue, urinary frequency, early satiety, abdominal bloating and distention
• PMH: HTN, medically treated with lisinopril
• SH: retired; grandmother of 3; never-smoker; social alcohol use
• PE: abdominal distention, bloating, and a positive fluid wave test; otherwise unremarkable

Clinical work-up

• Pelvic exam with transvaginal ultrasound showed a right ovarian mass
• Chest/abdomen/pelvis CT with contrast revealed a right adnexal 5.3-cm complex mass, a suspicious intraparenchymal liver lesion, retroperitoneal lymph node enlargement and concurrent pleural effusion
• Lymph node and adnexal mass biopsy confirmed high-grade, epithelial ovarian cancer; positive cytology of pleural effusion
  • T1N1M1
• Germline molecular testing showed BRCA1/2 wild-type, HRD+
• CA-125, 438 U/mL
• ECOG: 1

Treatment

• Patient underwent TAH/BSO, lymph node dissection, with suboptimal debulking; residual disease 1.3 cm
• Paclitaxel/carboplatin/bevacizumab + maintenance bevacizumab
  • After 3 cycles, patient underwent second debulking surgery, R0
• Continued on bevacizumab for 6 more cycles
  • Achieved partial response, post treatment CA-125, 40 U/mL
     

Follow-up

• At 3 months
  • CA-125, 18 U/mL
  • Chest/abdomen/pelvis CT showed no gross pelvic masses or nodes
  • Pelvic exam was unremarkable