Introduction Significant disparities in the diagnosis and treatment of ovarian cancer persist across different regions in China. County-level hospitals, which serve a large portion of the rural population, often face challenges such as limited medical equipment, a shortage of specialized professionals, and restricted access to novel drugs, leading to nonstandardized care and suboptimal patient outcomes. To address these challenges within the national policy context of tiered healthcare delivery, and based on the multiple national-level clinical practice guidelines,1–5 the National Cancer Center, the National Gynecological Quality Control Center and the National Cancer Quality Control Center of China commissioned the Ovarian Cancer Quality Control Expert Committee to draft the guideline. This guideline aims to standardize clinical practices and improve the prognosis and quality of life for patients in county-level healthcare settings. It adopts a practical, pathway-based approach covering the entire patient’s journey to provide clear and concise guidance for county-level clinicians. The core of the guideline is to establish a structured referral system while providing tailored protocols for diagnosis, treatment, and follow-up, thereby optimizing resource utilization and ensuring that patients receive care at the appropriate level. The classification of recommendations used in this guideline is shown in Supplementary Table 1, https://links.lww.com/CM9/C820. Tiered Diagnosis and Treatment Pathway for Ovarian Cancer in County-Level Regions In China, a significant portion of ovarian cancer cases occur in rural areas,6 where adherence to standard treatment protocols is often low. To address this disparity, a tiered diagnosis and treatment model is proposed to optimize medical resources, enable bidirectional referrals, and promote standardized care in county-level regions. Although the overall service level of many county hospitals has improved, challenges remain in managing complex, multidisciplinary diseases such as ovarian cancer,7–9 necessitating a clear framework for patient management and referral Supplementary Figure 1, https://links.lww.com/CM9/C820. Recommendation 1 County-level hospitals are primarily responsible for conducting initial diagnosis and treatment of ovarian cancer, antitumor drug therapy and maintenance treatment, as well as adverse event management, recurrence monitoring, rehabilitation guidance, two-way referrals, and patient follow-up. When they do not have the corresponding diagnostic and treatment capabilities and medical technology conditions, patients should be promptly referred to tertiary hospitals with the necessary conditions. County-level hospitals with the appropriate conditions and capabilities can carry out surgical treatment for early-stage ovarian cancer. If there is a strong suspicion of intermediate or advanced-stage ovarian cancer, they should be promptly referred to a tertiary hospital. All the following diagnostic and treatment pathways are based on this principle of upward and downward referrals. (Recommendation strength: 2A) Diagnostic Pathway for Ovarian Cancer in County-Level Regions The diagnosis of ovarian cancer is based on a comprehensive assessment including clinical evaluation, imaging, and histopathology. For patients with advanced disease or significant comorbidities, pretreatment evaluation by a multidisciplinary team (MDT) is strongly recommended to optimize the therapeutic strategy. Molecular testing is pivotal for guiding modern treatment. It is recommended that all patients with ovarian cancer, especially those with high-grade serous carcinoma, undergo testing for BRCA1/2 mutations and homologous recombination deficiency (HRD) status. Identification of BRCA mutations or HRD positivity is crucial, as it predicts sensitivity to platinum-based chemotherapy and poly-ADP ribose polymerase (PARP) inhibitors (PARPi). However, HRD testing has limitations, including uncertainties regarding the optimal cut-off values, variable assay reproducibility, and the potential for HRD-negative tumors to respond to targeted therapies. Furthermore, HRD assays primarily reflect genomic instability at a single timepoint, neglecting potential dynamic changes during disease progression or treatment. Thus, clinicians should interpret HRD test results in conjunction with clinical context, histological findings, and patient-specific factors. The diagnostic pathway for ovarian cancer is illustrated in Supplementary Figure 2, https://links.lww.com/CM9/C820. Recommendation 2 In instances where county-level hospitals lack the requisite imaging equipment or expertise in image interpretation, or when faced with complex cases, it is advisable to refer patients to the higher-level medical institutions or to utilize teleconsultation services. (Recommendation strength: 2A) Recommendation 3 To ensure precise histopathological results and essential molecular profiling (e.g., BRCA1/2 and HRD status), tumor samples should be sent to pathology departments of higher-level hospitals or accredited third-party laboratories, with telepathology consultation also recommended. (Recommendation strength: 2A) Recommendation 4 County-level hospitals should proactively establish and implement multidisciplinary integrated care for ovarian cancer, encompassing gynecology/gynecologic oncology, surgery, medical oncology, radiation oncology, pathology, and radiology departments. It is recommended that a multidisciplinary discussion be conducted before the initiation of treatment for patients with ovarian cancer, whether within the county hospital, at a higher-level institution, or through teleconsultation with a higher-level institution, to ensure both standardized and individualized oncologic care. (Recommendation strength: 2A) County-Level Ovarian Cancer Treatment Pathway of Newly Diagnosed Ovarian Cancer Surgery The initial treatment of ovarian cancer is centered on surgery, with the primary goals of achieving accurate staging for early-stage disease and maximal cytoreduction for advanced-stage disease. The main surgical strategies include primary cytoreductive surgery (PDS) for resectable tumors and neoadjuvant chemotherapy (NACT) followed by interval debulking surgery for patients with initially unresectable advanced disease. While open laparotomy is typically recommended when malignancy is suspected, a laparoscopic approach may be considered for diagnosis or staging in select early-stage cases. Regardless of the surgical approach, strict adherence to oncologic principles—such as avoiding intraoperative tumor rupture and using a specimen bag for removal—is crucial. For patients considered for NACT, a definitive pathological diagnosis must be obtained before commencing chemotherapy. A detailed surgical treatment pathway is illustrated in Supplementary Figure 3, https://links.lww.com/CM9/C820. Recommendation 5 Before any procedure, county-level hospitals must confirm their surgical and pathological staging capabilities. They may perform surgery for select early-stage cases (e.g., fertility-sparing) if institutional capacity allows, but should refer patients with advanced-stage disease to a higher-level hospital for surgical management. (Recommendation strength: 2A) Recommendation 6 Laparoscopic staging for early-stage cancer may be performed by experienced surgeons but requires strict adherence to oncologic principles, including tumor containment in a specimen bag and conversion to open laparotomy if surgical goals cannot be met. (Recommendation strength: 2A) Recommendation 7 Patients requesting prophylactic bilateral salpingo-oophorectomy should be referred to a center with appropriate expertise due to the procedure’s complexity, which involves comprehensive preoperative assessment and specialized pathological handling. (Recommendation strength: 2A) Chemotherapy Chemotherapy is a cornerstone of treatment for ovarian cancer, used in both neoadjuvant and adjuvant settings. The standard of care is platinum-based combination chemotherapy, typically paclitaxel and carboplatin. In certain scenarios, treatment may include the antiangiogenic agent bevacizumab, which must be discontinued at least 6 weeks before surgery, or an intraperitoneal/intravenous regimen for select patients with optimally debulked stage II–III disease. The specific regimen and number of treatment cycles are determined by disease stage and histology, with response monitored through tumor markers and imaging. A detailed chemotherapy pathway is available in Supplementary Figure 4, https://links.lww.com/CM9/C820. Recommendation 8 To standardize chemotherapy regimens and promptly identify and manage chemotherapy-induced hypersensitivity reactions (which have a higher incidence with paclitaxel and can be delayed with platinum agents), it is recommended that the first cycle of chemotherapy for newly diagnosed patients with ovarian cancer can be administered at a higher-level hospital or a same-level hospital with the appropriate capabilities. (Recommendation strength: 2A) Maintenance therapy First-line maintenance therapy is administered to patients with stage II–IV ovarian cancer who have achieved a complete or partial response after initial chemotherapy, with the goal of delaying recurrence and improving long-term survival. The selection of an appropriate maintenance strategy is highly individualized and depends on factors such as surgical–pathological stage and, crucially, molecular biomarker status. Testing for BRCA1/2 mutations and HRD is essential to guide the use of the primary therapeutic agents, which include PARP inhibitors and the antiangiogenic agent bevacizumab. A detailed pathway for maintenance therapy is provided in Supplementary Figure 5, https://links.lww.com/CM9/C820. Recommendation 9 Maintenance therapy should be selected based on the tumor molecular testing results to maximize patient’s benefit. Consideration must be given to drug accessibility and coverage under the national health insurance system. Additionally, for patients with germline BRCA mutations, it is essential to verify high-risk family members and provide comprehensive genetic counseling. This counseling should guide subsequent clinical management and potentially inform decisions regarding pregnancy. (Recommendation strength: 1) County-Level Ovarian Cancer Treatment Pathway of Recurrent Ovarian Cancer The management of recurrent ovarian cancer is challenging, and treatment is guided by classifying the types of recurrence. Based on the platinum-free interval (PFI)—the time from completion of the last platinum-based chemotherapy to disease progression—recurrence is primarily categorized as: (1) Platinum-sensitive recurrence (PSR): PFI of 6 months or more. (2) Platinum-resistant recurrence (PRR): PFI of less than 6 months. (3)Platinum-refractory disease: No response to initial therapy, with stable disease or disease progression, including progression within 4 weeks of completing chemotherapy. Management of patients with recurrent ovarian cancer is provided in the pathway depicted in Supplementary Figure 6, https://links.lww.com/CM9/C820. It is recommended that patients with advanced ovarian cancer undergo MDT evaluation not only before initial treatment, but at multiple key nodes throughout the treatment course, such as before surgery and upon suspicion of disease recurrence, as multidisciplinary collaboration can help develop a comprehensive, standardized, precise, multimodular, and individualized treatment plan. Treatment strategies diverge based on platinum sensitivity. For patients with PSR, management includes evaluating for secondary cytoreductive surgery, a decision best made at a higher-level hospital. The mainstay of medical therapy is retreatment with platinum-based combination chemotherapy, which may be combined with bevacizumab. Following a response, maintenance therapy with a PARP inhibitor or bevacizumab can be considered. In contrast, for PRR, where chemotherapy efficacy is limited, the primary goals of treatment are to extend survival and improve quality of life. The preferred options typically involve nonplatinum-based single-agent therapy, potentially combined with bevacizumab. Detailed treatment regimens for both PSR and PRR are available in the Supplementary Tables 2 and 3, https://links.lww.com/CM9/C820. Additionally, patients with PRR should be encouraged to participate in the clinical trials. Supplementary Table 4, https://links.lww.com/CM9/C820 summarizes the selected ongoing trials, highlighting key exploratory directions in this field, such as antibody-drug conjugates, targeted small molecules, and innovative immunotherapy combinations. Recommendation 10 For recurrent ovarian cancer, a comprehensive reevaluation is necessary to determine platinum sensitivity and formulate a treatment plan. It is recommended that county-level hospitals conduct a multidisciplinary consultation with a higher-level institution to guide this process. (Recommendation strength: 2A) Recommendation 11 For patients who have not previously undergone molecular testing, testing should be pursued to identify potential benefits from targeted therapies and to guide genetic counseling for at-risk family members. (Recommendation strength: 2A) County-Level Ovarian Cancer Follow-Up Pathway Lifelong follow-up is warranted for all patients with ovarian cancer due to the risk of recurrence. Surveillance includes regular clinical examinations, monitoring of serum tumor markers (e.g., CA-125 and HE4), and periodic imaging. The frequency of visits is highest in the first 2 years posttreatment and decreases over time. Throughout this process, the proactive management of treatment-related adverse events is crucial for ensuring patient’s safety and quality of life. A detailed follow-up pathway is outlined in Supplementary Figure 7, https://links.lww.com/CM9/C820. Recommendation 12 Routine surveillance for stable patients can be conducted at the county-level hospital, preferably the same institution that provided initial treatment. For ovarian cancer patients with stable disease, the county-level hospital should provide regular monitoring, rehabilitation guidance, and reminders for scheduled follow-up visits. If there is suspicion of local recurrence or distant metastasis, the patient should be referred to a higher-level hospital for comprehensive evaluation. To ensure consistency, it is advisable to perform consecutive imaging assessments at the same facility. (Recommendation strength: 2A) Recommendation 13 Given the potential transportation challenges faced by county-level patients, it is recommended to incorporate remote follow-up methods, such as telephone consultations and internet-based outpatient visits, in between in-person follow-up appointments. This hybrid approach will enable close monitoring of the patient’s clinical status and timely detection of any changes in their condition. (Recommendation strength: 2A) Steering committee Ding Ma (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Qinglei Gao (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Rutie Yin (West China Second University Hospital), Chunyan Wang (Liaoning Cancer Hospital), Ying Zhou (The First Affiliated Hospital of University of Science and Technology of China). Authors Qinglei Gao (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Rutie Yin (West China Second University Hospital), Chunyan Wang (Liaoning Cancer Hospital), Ying Zhou (The First Affiliated Hospital of University of Science and Technology of China), Dan Liu (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Zikun Peng (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Huayi Li (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology), Wenjing Yang (Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College), Juan Yang (Office for Cancer Diagnosis and Treatment Quality Control, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College), Ding Ma (Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology). Funding This work was supported by grants from the National Key Technology Research and Development Program of China (Nos. 2022YFC2704200 and 2022YFC2704205) and CAMS Innovation Fund for Medical Sciences (CIFMS) (No. 2021-I2M-1-001). Conflicts of interest None.
Gao et al. (Thu,) studied this question.