A new research study suggests that recurrence rates in low-grade serous ovarian cancer may be reducing with the introduction of better surgical management and the use of aromotase inhibitors as maintenance therapy in low-grade serous ovarian cancer.
“Our study, although retrospective and somewhat early, really serves as a beacon of hope for women with metastatic low-grade serous carcinoma.
If the findings hold, women who live 5 years without relapse will have a very low risk of relapse later. It also could mean that the oft-quoted relapse rates of 70-80% may be reduced to around 50%, signaling progress in our fight against this rare ovarian cancer subtype.
Ultimately, the ongoing phase 3 randomized trial—NRG-GY-019–will provide the best evidence.”
– Dr David Gershenson, MD Anderson Cancer Center
Trigger warning – this article discusses recurrence rates and survival statistics for low-grade serous carcinoma.
Who was included in the study?
The study included patients who had:
- Stage II to IV low-grade serous carcinoma confirmed by a gynaecological pathologist at MD Anderson Cancer Center
- Primary cytoreductive surgery (i.e. surgery to remove visible cancer before receiving any medical treatment), in most cases this included removal of the uterus, both ovaries/fallopian tubes and an omentectomy.
- Either platinium/taxane chemotherapy followed by aromotase inhibitor* (AI) maintenance therapy OR aromotase inhibitor mono therapy (i.e. without chemotherapy)
- At least 2 years of follow up
*Aromotase inhibitors are a class of medication that reduce estrogen production in post-menopause. Examples include letrozole, anastrozole and exemestane.
The study excluded patients with low-grade serous carcinoma who received chemotherapy prior to surgery (neo-adjuvant), and patients whose tumours had a P-53 mutation, or co-existent high-grade serous carcinoma.
In total there were 99 patients included in the study.
The study was retrospective. This means patient data was collected to look at things that had happened in the past, compared to a prospective study where patients are recruited and followed to see what happens to them in the future.
i.e. who were the people in the study
- Age: 20 were 35 years or younger, 79 were older than 35 when diagnosed
- Type: 49 had ovarian, 40 had primary peritoneal
- Stage: 9 had stage II, 80 had stage III, 10 stage IV
- CA125: 22 had a CA125 of 35 units/mL or less at diagnosis, 76 had a CA125 greater than 35units/mL
- Treatment: 84 had chemotherapy followed by AI, 15 were treated with an AI without chemotherapy
- Residual disease: 50 had no visible disease following surgery, 49 had some small visible disease following surgery
What did the study find?
- The median progression free survival (the point at which half of people in the study recurred and half had not) was 56.8 months
- The median overall survival was 130.7 months
- 49 patients (50%) had experienced a recurrence at the time of the study
- 50 patients had not recurred at the time of publication, including 14 with residual disease. Their median follow up time (i.e. time since diagnosis) was 86.2 months (confidence interval 67 to 105.2 months). 17 were diagnosed 2-5 years ago and 33 were diagnosed between 5 and 14 years.
- The recurrence rate in low-grade serous ovarian and peritoneal cancer was the same in people who received chemotherapy with AI, and people who only received AI but the AI only group had a greater proportion of recurrence free people diagnosed less than 5 years ago. The sample size is too small to draw any conclusions as to whether outcomes on both treatments are the same or not and we will need to wait for the results of the NRG-GY-019 clinical trial which is testing this question.
- None of the patients with stage II had experienced a recurrence at the time of publication (follow up range: 39.9 months to 169 months). Of the 10 patients with stage IV, 8 had recurred but one was still recurrence free at 117.1 months despite residual disease following surgery.
- Just one patient in the group has experienced a recurrence beyond 5 years (at 69.1 months, dying at 120.5 months)
What is the significance of this study?
Previously the recurrence rate of low-grade serous carcinoma has been estimated to be as high as 80% or more. This study suggests that the introduction of better surgery and aromotase inhibitors has reduced this high recurrence rate. The study found a recurrence rate of 50% but because 17% of patients had been followed for less than 5 years, the true rate is likely higher.
Of particular note, women diagnosed with stage II ovarian cancer in this study have done particularly well with none experiencing a recurrence to date. In addition one stage IV patient is an exceptional survivor remaining recurrence free nearly ten years after diagnosis.
Another interesting aspect of this study was that only one person had experienced a recurrence beyond 5 years. However, due to Aromotase Inhibitor use being relatively recent in low-grade serous cancer, most people included in this study were diagnosed less than ten years ago and the maximum follow up was 14 years.
Longer follow up and more research is needed to determine whether women receiving cytoreductive surgery and aromotase inhibitors who have not recurred by five years, and those with stage II, are unlikely to recur in the future, or if the risk of recurrence persists for a significantly long time. This is an important question because many women with low-grade serous cancer are diagnosed at a younger age and want 40-60+ years cancer free, to live a normal life expectancy.
This study also raises questions about the optimal length of time for someone to remain on an aromotase inhibitor in low-grade serous carcinoma. Should it be continued indefinitely if someone is experiencing a significant recurrence free period or stopped after a period of time as in breast cancer?
A particular strength was the gynaecological pathology review. Borderline tumours can be misdiagnosed as low-grade serous and skew results but the specialist gynaecology pathology review from MD Anderson Cancer Center means we can be confident that all of the patients in this study had “true” low-grade serous carcinoma.
This was a well designed retrospective study and in the context of the challenges of researching a rare cancer the participant numbers were reasonable. That said, it is worth keeping in mind from a statistical stand point the numbers in this study were small (particularly stage II, stage IV, AI only treatment) and it is possible that different and larger studies in the future might find different results.
“This is one of the most hopeful research papers I have read on low-grade serous ovarian. If the findings are confirmed in future studies it would be a huge step forward for women with our ovarian cancer.”
– Jane Ludemann, Founder Cure Our Ovarian Cancer
Original research paper: Contemporary primary treatment of women with stage II-IV low-grade serous ovarian/peritoneal cancer (LGSOC): Determinants of relapse and disease-free survival by David Gersnson, Lauren Cobb, Shannon Westin, Yingao Zhang, Amir Jazaeri, Anais Malpica and Charlotte Sun. Published in Gynaecologic Oncology 2022. Issue 167, page 139-145
This article was published in December 2022 and its content has been reviewed and approved by a co-author of the original research paper.