Editor’s Note:
Protecting the health of Chinese women and providing a robust defense against gynecological cancer requires the integration of more resources and efforts in the field of gynecological cancer prevention and treatment. On the eve of the “2023 Chinese Congress on Holistic Integrative Oncology (2023 CCHIO),” Oncology Frontier interviewed Prof. Zhong-Qiu Lin, Chairman of the Cervical Cancer Professional Committee of the China Anti-Cancer Association and Sun Yat-sen Memorial Hospital, to discuss the current status of gynecological cancer prevention and treatment in China, recent advances in maintenance therapy for advanced-stage cases, and the developmental vision of the Cervical Cancer Professional Committee of the China Anti-Cancer Association.
Oncology Frontier: Cervical cancer, ovarian cancer, and endometrial cancer are the three most common gynecological cancers. Could you please introduce the current situation of cancer prevention and treatment for women in China?
Prof. Zhong-Qiu Lin: Among the three major gynecological cancers, cervical cancer has the highest incidence, followed by endometrial cancer and ovarian cancer. Overall, the task of preventing and treating gynecological cancers in China remains substantial. Taking cervical cancer as an example, in 2020, there were 109,741 new cases of cervical cancer in China, with a standardized incidence rate of 10.7 per 100,000 people. There were over 59,000 new cases of cervical cancer-related deaths, with a standardized mortality rate of 5.3 per 100,000 people. The high incidence and mortality of cervical cancer are mainly related to several factors. First, more efforts are required for prevention improvement, as we have lower HPV vaccination rates compared to developed countries. Second, early screening outcomes vary across different regions. In some remote and underdeveloped areas, gynecological cancer screenings are inadequate, which hinders regular screening for the target population to interrupt the progression of cervical cancer. Third, there are regional disparities in the treatment of cervical cancer, with insufficient radiotherapy equipment and surgical expertise in remote and underdeveloped areas, posing a serious challenge to improving the survival rates of cervical cancer patients.
Among the three major gynecological cancers, endometrial cancer has a relatively higher early diagnosis rate because it features evident early symptoms such as abnormal vaginal bleeding, thus leading to better treatment outcomes. Ovarian cancer, on the other hand, is more insidious and represents a weak point in our gynecological cancer prevention and treatment. In 2020, there were over 55,000 new cases of ovarian cancer in China, resulting in over 37,000 deaths. China has the highest number of new cases of ovarian cancer and ranks high in terms of ovarian cancer mortality worldwide. Therefore, the prevention and treatment of gynecological cancers in China requires collaborative efforts from various sectors to improve prevention, screening, diagnosis, and treatment and provide better health protection for women.
Oncology Frontier: ” Cancer Control, Winning in Integration ” is the cancer prevention and treatment concept upheld by the China Anti-Cancer Association. How do you think this integrative medical approach can be applied in the diagnosis and treatment of gynecological cancers?
Prof. Zhong-Qiu Lin: The application of holistic medicine in cancer prevention and treatment can be summarized as “prevention, screening, diagnosis, treatment, and recovery”. We should approach patients holistically, not only diagnosing and treating the disease but also assisting in their physiological and psychological recovery, enabling them to return to a normal or near-normal state of life and continue fulfilling their roles in their families, society, and work. This process involves not only clinical doctors but also nursing, rehabilitation, and psychological experts, as well as the involvement of public welfare and community organizations.
Prevention is a key focus of cancer prevention. Cervical cancer prevention serves as a paradigm for solid tumor prevention. In clinical practice, over 90% of cervical cancer cases are associated with high-risk HPV infections. HPV vaccines effectively prevent cervical cancer and provide a well-established method for etiological prevention. In fact, the progression from HPV infection to the development of cervical cancer occurs over an extended period, providing a substantial window for screening. Cervical cancer prevention and screening need to be implemented at the national level, including immunization planning and free screenings for eligible women, which also require the integration of more resources and efforts.
Therefore, integrative medicine is practical and effective in the prevention and treatment of gynecological cancers, especially in the prevention of cervical cancer, where it can fully encompass the entire process of “prevention, screening, diagnosis, treatment, and recovery.” It is hoped that the introduction of these new concepts can reduce the incidence of gynecological cancers, providing more comprehensive treatment and recovery for gynecological cancer patients, and enabling them to return to society and integrate into life more effectively.
Oncology Frontier: PARP inhibitors (PARPi) have become the standard for first-line maintenance therapy for ovarian cancer. How do you view the impact of PARPi on the diagnosis and treatment of ovarian cancer, and can the “maintenance therapy” model be applied to other gynecological cancers, such as cervical cancer?
Prof. Zhong-Qiu Lin: PARPi is a new type of targeted therapy that kills tumor cells by using the “synthetic lethality” concept, which can prevent tumor cells from repairing themselves. It has now become the standard for first-line maintenance therapy in ovarian cancer, mainly used in patients with BRCA mutations and homologous recombination repair defects (HRD). We know that the majority of ovarian cancer cases are diagnosed at an advanced stage. Even after surgery and chemotherapy, approximately 75% of patients experience recurrence within three years. Our treatment strategy aims to delay tumor recurrence and progression, but surgery and chemotherapy are limited and not suitable for long-term maintenance therapy. PARPi, administered orally, is convenient, and its efficacy and safety have been clinically validated, making it an ideal drug for maintaining ovarian cancer. The SOLO-1 study showed that in newly diagnosed ovarian cancer patients with BRCA mutations who received maintenance therapy with the PARPi olaparib after surgery and chemotherapy, the progression-free survival (PFS) was significantly extended by 42.2 months (56.0 vs. 13.8 months, HR 0.33, 95% CI: 0.25~0.43). In other words, olaparib can delay the recurrence and progression of disease by more than three and a half years. Particularly encouraging is the 7-year follow-up in the study, where patients in the olaparib group had a 7-year overall survival rate of up to 67%, with a significant 45% reduction in the risk of death (NR vs. 75.2 months, HR 0.55, 95% CI: 0.40~0.76; P=0.0004). This means that nearly 70% of patients can achieve long-term survival of over seven years.
The occurrence of BRCA mutations in cervical cancer patients is relatively low, so PARPi is not routinely used. However, the maintenance therapy model is also applicable to cervical cancer. In late-stage cervical cancer patients who have completed chemotherapy with the anti-angiogenic drug bevacizumab, bevacizumab can be continued as maintenance therapy. However, it only delays disease recurrence and progression by a few months, which is not as pronounced as that of PARPi in ovarian cancer maintenance therapy. In recent years, the addition of PD-1/L1 immune checkpoint inhibitors to maintenance therapy has achieved good results. Additionally, some small molecule TKIs are also used for maintenance therapy in cervical cancer, but overall, none of these options have shown the outstanding effects of PARPi in ovarian cancer maintenance therapy.
Endometrial cancer is similar to cervical cancer, primarily utilizing immunotherapy or anti-angiogenic drugs for maintenance therapy. There are also preliminary studies exploring the use of PARPi for maintenance therapy. For example, the UTOLA trial in stage IIb endometrial cancer patients reported at the 2023 ESMO Congress (Abstract LBA42) showed that olaparib maintenance therapy could extend the PFS of HRD-positive advanced-stage endometrial cancer patients (5.4 vs. 3.6 months, HR 0.59, P=0.02), warranting further research and validation.
