Diagnosis of Metastatic Platinum-Resistant Ovarian Cancer

Robert L. Coleman, MD:This case is a little bit unusual. It’s a 38-year-old woman who presents with, unfortunately, what are very common symptoms for ovarian cancer: abdominal bloating, a distension, and abdominal pain. It’s not uncommon for women to have these kinds of symptoms for several months before medical evaluation takes place. Obviously, there was something abnormal that was found on her exam, and that prompted a series of next steps. The first next step was that blood was drawn to test for CA-125, which is not uncommon to test for when the suspicion is ovarian cancer. And the second step was that she had imaging done to evaluate the areas that this disease had spread to, which are most commonly in the abdominal cavity.

I think, going through the clinician’s mind at the time of presentation, that you have a young woman, and young women are not in the usual spectrum of patients who have advanced epithelial ovarian cancer, so other ovarian malignancies need to be under consideration. Frequently, what we would draw in addition to CA-125 would be other markers for germ cell tumors, to make sure that was completely ruled out.

Nevertheless, she does get an imaging study done, which shows that she has intra-abdominal disease. The disease is typically bulky, and that was the case in this particular patient. It was seen with ascites and in large volume in the upper abdomen, and that’s very common in the distribution of the intraperitoneal carcinomatosis that we see in women who have high-grade serous carcinoma or have an ovarian cancer malignancy that’s spread. Then, I think an important event happened: she was referred to a gynecologic oncologist. So, sometimes these patients are first introduced into the system through their gynecologist, or they may be introduced into the system through their internist.

We think one of the key pieces in the management of women who have ovarian cancer is that they’re referred to a gynecologic oncologist who can make the decision as to whether or not surgery should be done. And, if surgery is chosen, they understand what the goals of that surgery are. In this case, the patient was seen and was taken to surgery, and she had a complete resection of visible disease. In that process, there were several decisions that needed to be made. One, that this was a resectable process; two, that a diagnosis needed to be made; and three, that the patient was taken to surgery and had a complete resection of all tumors. That is really our ultimate goal in what we would now consider an optimal cytoreduction. So, from that standpoint, she received the best initial care that she could get.

Then, the diagnosis was confirmed: in this case, it was endometrioid ovarian cancer, and that is one of the histology subtypes that we see with ovarian cancer. The most common—what I call the vanilla—of the ovarian cancer epithelial tumors is usually of the serous variety. In this particular case, it was a slightly unusual type, endometrioid, and endometrioid is just like it sounds. The “oid” part of “endometrioid” means “like,” and like in endometrioid means like the uterus.

So, endometrioid tumors are cells that, under the microscope, will look very endometrial in their shape and their character. These types of lesions are seen in young women, particularly in young women who have epithelial ovarian cancers and are rising in endometriosis. You may hear this term sometimes as cancer rising endometriosis, and the cell types we see that typically accompany that pathology are endometrioid or clear-cell tumor. So, she presents an unusual cell type, but that would be consistent with her young age at presentation.

Then, I think the last important step that was done as part of this initial evaluation and treatment was that she was tested forBRCAgenes. We have now learned that family history and personal history can only provide so much of the information that’s necessary to identify all patients that potentially carry theBRCAaberrations in the BRCA genes in the germline.

In younger-aged women, we certainly expect that this fits the profile for germline mutations, but 38 is actually a young age even among the cohort of patients that are identified withBRCA1orBRCA2germline mutations. However, it’s not that unusual to see aberrations of this type in some of the cell types other than serous carcinomas in the ovary.

So, I do think that this is a reasonable thing to do. It was done, and she was found to beBRCA1andBRCA2negative. While people may say, “Wow, that’s unusual because she’s so young,” in the endometriosis associated cancers, if that’s what this case is, it wouldn’t necessarily be that unusual. It would be associated with young age, but not necessarily associated with theBRCA1orBRCA2mutations.

Transcript edited for clarity.

July 2016

• A 38-year old female presented to her gynecologist with abdominal distension, abdominal pain, fullness after eating, and increased urination frequency for 2 months
  • Pelvic examination revealed a suspicious mass on the left ovary
• Laboratory findings:
  • CA-125: 785 U/ml
  • Genetic testing forBRCA1/2, negative
• CT with contrast of the pelvis, abdomen, and chest indicated widespread peritoneal lesions
• She was referred to gynecologic oncology and underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking; She had diffuse studding in the omentum and diaphragmatic surfaces
• Stage 3C ovarian cancer
• She achieved complete removal of gross residual disease (R0)
• Pathology, high-grade endometrioid adenocarcinoma, ovarian primary
• The patient was started on therapy with carboplatin and every-3-weekly paclitaxel

October 2016

• Post-treatment assessment revealed no evidence of disease

March 2017

• Patient complained of fatigue and chest pain
• Physical examination:
  • Lungs, moist rales bilaterally
  • Abdomen, shifting dullness
• Laboratory findings: CA-125: 1,052 U/ml
• CT imaging: left-sided pleural effusion and sclerotic lesions in the lung apical region, ascites, new hypodense lesions in the right lobe of the liver and enlarged retroperitoneal nodes were considered metastatic
• She was started on therapy with weekly paclitaxel and bevacizumab