Predicting Treatment Effectiveness for High-Recurrence Ovarian Cancer with a Simple Blood Test

Providing Evidence for Selecting Candidates for Hyperthermic Intraperitoneal Chemotherapy (HIPEC)

The team led by Professor Hyunwoong Cho from the Department of Obstetrics and Gynecology at Asan Medical Center in Seoul announced on December 19 that, after analyzing blood test data from 213 patients with stage 3 or higher ovarian cancer, they found that patients with a low response to chemotherapy who received HIPEC treatment had a 58% lower risk of ovarian cancer recurrence and a 71% lower risk of death compared to those who did not receive the treatment.

Hyunwoong Cho, Professor of Obstetrics and Gynecology at Asan Medical Center, Seoul. Asan Medical Center, Seoul

The research team confirmed that hyperthermic intraperitoneal chemotherapy (HIPEC) was particularly effective in patients whose tumors shrank relatively slowly during preoperative chemotherapy.

This study is expected to contribute to improving treatment efficiency and overall survival rates by providing evidence that a simple blood test can help predict which ovarian cancer patients would benefit from HIPEC treatment.

Ovarian cancer has the highest mortality rate among gynecologic cancers. It is a refractory cancer with a high recurrence rate and a five-year survival rate of less than 50%. Because it rarely presents specific early symptoms, about 80% of patients are diagnosed only at advanced stages (stage 3 or 4), when the cancer has already spread throughout the abdominal cavity.

HIPEC treatment involves opening the abdomen to remove visible tumors, then infusing heated chemotherapy drugs (at approximately 42 degrees Celsius) into the abdominal cavity to destroy even microscopic cancer cells. While this method, which administers high-temperature chemotherapy during surgery, carries a risk of complications, it is effective at eliminating heat-sensitive cancer cells. However, there has been no biomarker to predict which ovarian cancer patients would benefit most from HIPEC treatment.

During chemotherapy for ovarian cancer, blood tests are regularly used to measure the level of the tumor marker CA125. CA125 is a substance that abnormally increases in the blood when ovarian cancer occurs and decreases as tumors shrink with chemotherapy, making it a useful indicator for assessing chemotherapy effectiveness.

The research team analyzed blood test data from 213 patients with stage 3 or 4 ovarian cancer who underwent at least three CA125 tests within the first 100 days of chemotherapy. To track changes in CA125, they used the KELIM predictive marker developed by researchers at the University of Lyon in France. This predictive marker mathematically quantifies the rate of CA125 decline during chemotherapy, with lower values indicating a poorer tumor response to chemotherapy.

Of the 213 patients, 159 received HIPEC treatment after tumor removal surgery, while 54 underwent only tumor removal surgery. The team classified patients using a predictive marker index of 1.0 as the threshold: those below 1.0 were categorized as the 'low chemotherapy response group,' and those at or above 1.0 as the 'high chemotherapy response group.' They then compared the effects of HIPEC treatment between these groups.

As a result, in the low chemotherapy response group, the risk of ovarian cancer recurrence was reduced by 58% and the risk of death by 71% compared to the non-HIPEC group. The median progression-free survival was about 10 months in the non-HIPEC group, but approximately 20 months-twice as long-in the HIPEC group. In terms of overall survival, the non-HIPEC group had a median survival of about 45 months, while more than half of the patients in the HIPEC group survived beyond the observation period, making it difficult to determine the median survival time.

Notably, among the low chemotherapy response group, the benefits of HIPEC treatment were especially pronounced in elderly patients aged 60 or older, those with high-grade serous ovarian cancer, and those with stage 4 disease.

In contrast, among the high chemotherapy response group, there was no statistically significant difference in survival based on whether or not HIPEC treatment was administered. In other words, patients who respond well to chemotherapy can achieve sufficient outcomes with standard chemotherapy alone, while those who do not respond to chemotherapy can improve their survival rates through HIPEC treatment.

Professor Hyunwoong Cho stated, "Chemotherapy plays a central role in treating ovarian cancer, but the prognosis for the low chemotherapy response group is often poor even after surgery and chemotherapy. This study is significant in demonstrating that combining surgery with HIPEC treatment can effectively reduce the risks of recurrence and death in these patients."

This study was recently published in the International Journal of Gynecological Cancer (impact factor 4.7), a prestigious international journal in the field of gynecologic oncology.