The Lack of Progress in Ovarian Cancer

Although the 5-year survival rate has notably improved for tumors that are not extremely aggressive, such as breast cancer, which improved from 75% in 1980 to 90% in 2010, and also for very aggressive neoplasms like pancreatic cancer, which improved from 5% in 1980 to 24% in 2010, it is really disheartening to see that the 5-year survival rate for ovarian cancer has not changed in 30 years; it has been steady between 39% and 45%. How is this possible when several groups of gynecologic researchers have been working on ovarian cancer all this time? I think there is a very simple explanation. All the research work so far has been concentrated in areas that do not have an impact on patient survival.

Most of the research has been done on serous carcinoma, which is the most common high grade ovarian cancer. This research has been concentrated in two areas: the origin of ovarian cancer from the fallopian tube and simplification of terminology.

Around the year 2000, Drs. Crum and Kurman proposed the theory that serous carcinoma of the ovary originated in reality from the fallopian tube. We were not aware of this possibility because we had not been submitting fallopian tube samples using a special protocol. After 16 years of using this special protocol, Dr. Crum realized that only 21% to 31% of high grade serous carcinomas had a lesion designated as STIC in the fallopian tube. In 2015, he wrote a paper saying that STIC is seen in 40% of the cases of high grade serous carcinoma. After 15 years of research, we went back to the ovary as the origin for most extrauterine serous carcinomas.

The second area where research was concentrated was the terminology for serous carcinoma. Well known gynecologic pathologists, occupying important positions in the Gynecologic Pathology Society made the simplification of the diagnosis of serous carcinoma a high priority . The idea was to bring uniformity to the diagnosis. Since some entities that they wanted to include under the term “papillary serous carcinoma” were not papillary, the suggestion was made to drop “papillary” from the classical name of papillary serous carcinoma. Since there were questions about the site of origin of serous carcinoma (the fallopian tube, the ovaries or the peritoneum), they suggested referring to all extrauterine serous carcinomas as pelvic. Regarding histology, they suggested that ovarian cancer that was not endometrioid, clear cell, mucinous, or pure undifferentiated should be designated as serous carcinoma and that therefore, focal undifferentiated, microcystic or transitional cell carcinomas should also be classified as serous carcinoma.

I disagree with the above approach. Gynecologic Pathologists should have learned from other subspecialties. In the 70’s, there were 4 types of lymphomas; today there are 74. In the 70’s, there was only 1 type of renal cell carcinoma; today there are 18. The subclassification of these tumors into many types has been a giant step forward in identifying differences in diagnosis, immunostains, molecular changes, prognosis and treatment.

In ovarian cancer, we have spent 15 years arguing about the fallopian tube as the origin and trying to achieve a uniform diagnosis. Neither one of these approaches has a direct impact on the survival rate of high grade ovarian cancer. A change in the direction of the research is needed. The first step is to separate high grade ovarian cancer based on H&E features. Then immuno and molecular techniques should be used. In this way, we will most probably be able to identify differences that will eventually help separate out cases with different markers, different prognoses and different treatments. Then, at this point, I hope we will see an improvement in the survival rate of high grade ovarian cancer.