The National Comprehensive Cancer Network (NCCN) is a non-profit academic organization composed of 21 top oncology centers in the United States, and its annually updated clinical practice guidelines for various malignancies have been recognized and followed by oncologists in various countries. These two guidelines have brought together a lot of efforts and wisdom of the Chinese expert group, and they are also respected and valued by their American counterparts, and some views of the Chinese expert group have been adopted by the original guidelines.
Like the English version, the NCCN Clinical Practice Guidelines for Ovarian Cancer (Chinese version) (hereafter referred to as the Guidelines) include three parts, namely, clinical management of epithelial ovarian cancer (including fallopian tube cancer and primary peritoneal cancer), junctional epithelial ovarian tumors (low malignant potential), and rare pathologic histologic types of ovarian tumors. The guidelines follow a clinical approach with clear “decision tree” guidelines on clinical presentation, examination and diagnosis, initial treatment, postoperative treatment, management after completion of standard treatment, follow-up and management after recurrence.
Since ovarian cancer has atypical clinical symptoms, the Guidelines recommend assessing patients’ family history and performing the necessary imaging and tumor marker tests.
Initial treatment Initial treatment is based on surgery, including full staging surgery and tumor cytoreductive surgery. Preservation of the uterus and contralateral adnexa may be considered for patients with clinical stage IA or IC (various degrees of differentiation) who require preservation of reproductive function. Both full staging surgery and cytoreductive surgery for extra-pelvic abdominal metastatic nodes ≤2 cm require resection of retroperitoneal lymph nodes (bilateral pelvic and para-aortic lymph nodes) for accurate staging, and that the para-aortic lymph nodes are resected at least to the level of the inferior mesenteric artery and preferably to the level of the renal vessels. The 2010 edition of the guidelines continues to emphasize the importance of initial tumor cytoreduction, suggesting specific quantitative documentation of the size and extent of primary and residual tumor lesions, and clearly defining “satisfactory cytoreduction for residual tumor foci <1 cm in maximum diameter. The definition of "residual tumor foci <1 cm is considered satisfactory cytoreduction". In order to achieve satisfactory cytoreduction (at all stages), expanded tumor cytoreduction procedures including pelvic and abdominal organ resection can be considered, and the recommendation of "partial liver resection, cholecystectomy, partial gastrectomy, partial cystectomy, and ureterocystectomy" was added in the 2010 edition.
The 2010 edition of the Guidelines specifically suggests that minimally invasive surgery can be used for prophylactic oophorectomy.
Postoperative chemotherapy The decision of postoperative chemotherapy or not is based on the pathological stage of the tumor and the degree of pathological differentiation. Stage I high-risk cases (poorly differentiated and stage IC) are given 3-6 courses of chemotherapy, while low-risk cases do not require chemotherapy; stage II-III patients should be given 6-8 courses of chemotherapy. The recommended first-line chemotherapy regimens are all paclitaxel combined with platinum, including intraperitoneal chemotherapy.
Based on the results of a Japanese randomized controlled study (RCT) published in The Lancet in 2009, a dose-dense weekly paclitaxel regimen [paclitaxel 80 mg/m2 , repeated on days 1, 8, and 15; carboplatin AUC (area under the drug-time curve) = 6, day 1] was added to the 2010 Guideline. This study showed that weekly paclitaxel therapy prolonged the progression-free survival (PFS) period by 10.8 months and improved 3-year survival by 7% compared with the conventional 3-week regimen.
Although some NCCN member institutions select chemotherapy regimens by chemosensitivity or resistance testing, with the current level of evidence, chemotherapy regimens selected by drug sensitivity testing are not yet sufficient to replace standard regimens.
Preoperative chemotherapy The Guidelines only recommend preoperative neoadjuvant chemotherapy for patients with stage III/IV ovarian cancer whose tumors are too large for immediate surgery and require that confirmatory pathologic histologic evidence (which can be obtained by fine needle aspiration, biopsy, or ascites puncture) be obtained before chemotherapy is administered to the patient.
Patients with stage II to IV who achieve complete clinical remission after initial treatment
For these patients, the recommended management plan of the Guidelines is to observe follow-up or participate in clinical trials, and it is controversial whether to give consolidation therapy, which can be considered as paclitaxel monotherapy (paclitaxel 135 mg/m2 , repeated every 4 weeks). Secondlook surgery was not recommended in the Chinese version of the guidelines and was removed from the original 2010 edition.
Preliminary data are available from a European multicenter study exploring the use of cancer antigen 125 (CA125) for monitoring patients completing initial treatment for ovarian cancer, but the Society of Gynecologic Oncologists (SGO) notes that the study has limitations and that patients should be made aware of the pros and cons of CA125 when used to monitor for recurrence. For cases where CA125 alone is elevated during follow-up and imaging and clinical tests are negative, three management options are recommended in the Guidelines: the first choice is to enroll the patient in a clinical trial, or to delay treatment until clinical relapse, or to administer chemotherapy immediately. the results of a European RCT reported at the American Society of Clinical Oncology (ASCO) Congress in 2009 showed that, compared with delayed treatment Immediate chemotherapy after CA125 elevation did not improve survival, and this result can be used as a reference when making clinical decisions.
Persistent and recurrent ovarian cancer For this type of ovarian cancer, the Guidelines emphasize the importance of individualized staging and state that the best option for patients with recurrence is to participate in a clinical trial.
The 2009 edition of the Guidelines classifies recurrent ovarian cancer into four types, namely, recalcitrant (tumor progresses or stabilizes during the first chemotherapy), drug-resistant (tumor is in complete remission but recurs within 6 months after stopping chemotherapy or is in partial remission), partially sensitive (tumor is in complete remission and recurs 6 to 12 months after stopping chemotherapy), and sensitive (tumor is in complete remission and recurs >12 months after stopping chemotherapy). For recalcitrant and resistant patients, non-platinum-based single-agent chemotherapy can be applied to prolong the interval of platinum-free chemotherapy, reduce toxicity and improve patients’ quality of life. For sensitive and partially sensitive patients, platinum-based combination chemotherapy can be chosen.
The 2010 edition of the Guidelines added two new combination regimens, paclitaxel peri-therapy + carboplatin and doxorubicin liposome + carboplatin, and emphasized the role of re-tumor cytoreductive surgery. For patients in complete remission for >6 months, re-tumor cytoreduction should be considered in all patients with resectable recurrent lesions.
Intersecting epithelial ovarian cancer This is a type of ovarian tumor with low-grade malignant potential. The principles of surgical treatment are similar to those of epithelial ovarian cancer, but the conditions for preservation of reproductive function have been relaxed, and patients with fertility requirements in stages I-IV are eligible for full-stage surgery to preserve reproductive function.
In addition, the Chinese version adds the statement that “for patients with junctional tumors in clinical stage I and without exophytic ovarian tumors, retroperitoneal lymph node dissection can be considered after careful exploration.
The most important basis for postoperative management is the presence or absence of infiltrative implantation on pathological examination, and in general, chemotherapy is not required after surgery, but only follow-up observation. If the pathology shows infiltrative implants, either observation or treatment of epithelial ovarian cancer is an option, but there is insufficient evidence to support the benefit of such treatment.
Rare pathologic histologic types of ovarian tumors This group includes ovarian germ cell tumors, ovarian gonadal interstitial tumors, and mixed mullerian tumors of the ovary (carcinosarcomas).
For ovarian germ cell tumors, full staging surgery with preservation of reproductive function can be applied to patients of any stage. For patients with stage I asexual cell tumors and stage I well-differentiated immature teratomas, postoperative chemotherapy is not available; whereas for patients with embryonal tumors, endodermal sinus tumors, stage II-IV asexual cell tumors, and stage I G2-3 or stage II-IV immature teratomas, postoperative chemotherapy should be administered. The regimen can be BEP (bleomycin + pedialyte glycoside + cisplatin, 5 days) for 3~4 courses of treatment. For some patients with stage IB-III anaplastic cell tumors, it is crucial to reduce the toxicity of chemotherapy and the EP regimen (pegylated glycosides + cisplatin, 3 days) can be applied for 3 courses of treatment.
The principles of surgical treatment of interstitial tumors of the ovarian sex cord are basically the same as those of epithelial ovarian cancer. Based on a study published in 2009 on the metastatic pattern of this type of tumor, the 2010 edition of the Guidelines recommends that lymph node dissection may be considered in fully staged surgery.