| disease | Ovarian Cancer |
| alias | Malignant Tumor of Ovary |
Ovarian cancer is one of the common tumors of the female reproductive system, ranking third in incidence after cervical and uterine corpus cancers. However, it accounts for the highest mortality rate among all gynecological tumors, posing a serious threat to women's lives. Due to the complex embryonic development, tissue anatomy, and endocrine functions of the ovaries, the tumors they develop can be either benign or malignant. Because ovarian cancer often presents no symptoms in its early clinical stages, distinguishing its tissue type and determining whether it is benign or malignant is quite challenging. During exploratory laparotomy for ovarian cancer, tumors confined to the ovaries are found in only 30% of cases, while most have already spread to the uterus, bilateral adnexa, the greater omentum, and pelvic organs. Thus, ovarian cancer remains a significant challenge in both diagnosis and treatment. Over the years, experts have extensively studied the pathological morphology, clinical progression, and treatment protocols for malignant ovarian tumors, accumulating substantial experience. To date, according to clinical statistics both domestically and internationally, the five-year survival rate remains only 25–30%.
bubble_chart Pathological Changes
The complexity of ovarian tumor histomorphology surpasses that of any other organ, which is due to: ① The ovarian tissue structure has a potential for highly versatile development; ② During embryogenesis, the ovary is very close to the urinary system, and part of the mesonephric tissue can become misplaced into the ovary; ③ The ovary originates from the embryonic genital ridge, which is homologous in both sexes and only differentiates later. There are many classification methods for ovarian tumors, and this chapter adopts a clinically practical classification based on histogenesis.
(1) Malignant tumors of the ovary derived from the germinal epithelium (paramesonephric coelomic epithelium), such as serous adenocarcinoma, mucinous adenocarcinoma, endometrioid adenocarcinoma, mixed serous-mucinous cystadenocarcinoma, fibroadenocarcinoma, malignant Brenner tumor, paramesonephric clear cell carcinoma, undifferentiated (anaplastic) carcinoma, etc. These tumors sometimes exhibit luteinization.(2) Malignant tumors of the ovary derived from germ cells, such as teratocarcinoma, primary choriocarcinoma, dysgerminoma, etc., which can sometimes secrete hormones.
(3) Malignant tumors of the ovary derived from sexually undifferentiated mesenchyme, such as benign tumors 1-6 with the same name as fleshy tumors, malignant mixed mesodermal tumors, and carcinosarcoma.
(4) Malignant tumors of the ovary derived from sexually differentiated mesenchyme, which have the function of producing autologous hormones and are also called functional tumors, all of which are potentially malignant.
1. Feminizing mesenchymal tumors: including ① granulosa cell tumor; ② theca cell tumor; ③ granulosa-theca cell tumor.
2. Masculinizing mesenchymal tumors: including ① Sertoli-Leydig cell tumor; ② hilus cell tumor.
3. Biphasic differentiation: gynandroblastoma.
(5) Malignant tumors of the ovary arising from mesonephric remnants, such as malignant mesonephroma.
(6) Malignant tumors of the ovary arising from ectopic tissues within the ovary, such as malignant adrenal cell rest tumor.
bubble_chart Clinical Manifestations
Malignant ovarian tumors often have no early symptoms, and by the time symptoms appear, the disease is usually at an advanced stage. Due to rapid tumor growth, abdominal distension and fullness, abdominal masses, and ascites may develop within a short period. When the tumor infiltrates surrounding tissues or compresses nerves, it can cause abdominal pain, lumbago, or sciatica. If pelvic veins are compressed, lower limb edema may occur. Menstrual disorders are generally uncommon, but if both ovaries are destroyed by cancerous tissue, it can lead to menstrual irregularities and amenorrhea. Additionally, if the tumor is functional, it may produce symptoms of excessive estrogen or androgen, such as precocious puberty, dysfunctional uterine bleeding, postmenopausal vaginal bleeding, or masculinization. Patients in the advanced stage often exhibit significant weight loss, severe anemia, and other cachexia symptoms. During a gynecological examination, scattered hard nodules may be palpated in the vaginal posterior fornix. The masses are usually bilateral, solid, irregular in surface, immobile, and often accompanied by bloody ascites. Sometimes, enlarged lymph nodes may be felt in the groin, armpit, or above the clavicle.
(1) Early Diagnosis Due to the absence of typical symptoms and signs in the early stages of malignant tumor of the ovary, detailed medical history inquiries, thorough physical examinations, and gynecological evaluations remain critically important. Clinically, if suspicious conditions arise, modern imaging techniques and broad-spectrum tumor marker tests should be utilized to achieve an early diagnosis. Suspicious conditions may include prolonged ovarian dysfunction, unexplained long-term gastrointestinal or urinary symptoms, ovarian enlargement in young girls or postmenopausal women, or rapid growth, fixation, or hardening of a previously suspected ovarian tumor.
(2) Localization Diagnosis For cases where an adnexal mass can be palpated early, localization diagnosis is not difficult when combined with imaging examinations. However, in some cases, small primary tumors may already have extra-ovarian metastases, forming scattered small nodules in the pelvic cavity. In such instances, specialized diagnostic methods should be selected to aid in qualitative diagnosis, rather than relying solely on follow-up observations and delaying treatment.
(3) Qualitative Diagnosis Despite the continuous advancement of diagnostic technologies, basic examinations such as vaginal posterior fornix fluid smear tests, cul-de-sac puncture fluid analysis, and ascites cytology remain simple, practical, and rapid diagnostic tools. For suspicious cases, laparoscopy and histological examinations can provide immediate clarification. Imaging studies, particularly vaginal ultrasound scans, can assist in qualitative diagnosis by delineating the boundaries (extent of involvement) and internal structure (nature) of early-stage malignant tumors of the ovary. Endocrine testing is useful for diagnosing ovarian gonadal stromal tumors and some ovarian cancers associated with ectopic endocrine syndromes. Serum tumor marker tests such as CA125, CEA, SONA, and SGA exhibit high sensitivity but low specificity for malignant tumors of the ovary. Therefore, a single immunological test cannot determine the tumor type. However, combined testing of multiple tumor markers—such as simultaneous measurement of CA125, CEA, ferritin, and tissue polypeptide antigen (TPA)—can improve the reliability of qualitative diagnosis.
(1) Treatment Principles: The primary treatment for malignant ovarian tumors is surgery, supplemented by comprehensive therapies such as radiotherapy and chemotherapy.
(2) Surgical Treatment: During surgery, a detailed exploration should first be conducted, including peritoneal lavage, palpation of pelvic and abdominal organs, retroperitoneal lymph nodes, and multiple biopsies of the diaphragm, peritoneum, and omentum to accurately stage the tumor. Surgical approaches are divided into radical surgery and fertility-sparing conservative surgery. Radical surgery involves bilateral adnexectomy, hysterectomy, omentectomy, appendectomy, and pelvic and retroperitoneal lymphadenectomy. For patients with extensive pelvic tumor metastasis, cytoreductive surgery is recommended whenever possible. Williams et al. reported that the complete remission rate for postoperative chemotherapy was 83% in patients with complete tumor resection, 59% in those with near-complete resection (residual tumor diameter <2 cm), and 42% in those with partial resection (residual tumor diameter >2 cm). Therefore, although malignant germ cell tumors are sensitive to combination chemotherapy, complete tumor resection during surgery remains a key factor for successful treatment.
(3) Chemotherapy: Due to the early spread of ovarian tumors, most cases cannot achieve complete tumor removal during surgery, and the efficacy and application of radiotherapy are limited. Thus, systemic chemotherapy is an important adjuvant treatment. In some advanced-stage patients, chemotherapy can shrink tumors, creating favorable conditions for subsequent surgery.
There is no standardized chemotherapy regimen for malignant ovarian tumors to date. The principles are: ① High-dose intermittent therapy is superior to low-dose continuous therapy. The former involves about one week of medication per cycle with a 3–4 week interval, achieving effective antitumor effects while allowing the body to eliminate toxicity and restore immune function. ② Combination chemotherapy is more effective than single-agent chemotherapy. Modern trends favor combination therapy, but attention must be paid to its heavier toxic reactions. ③ Selecting sensitive chemotherapy drugs based on drug sensitivity tests can prolong patient survival. ④ Different chemotherapy regimens should be tailored to histological types. In recent years, common chemotherapy regimens for ovarian cancer are as follows:
1. Epithelial carcinoma and sex cord-stromal tumors often use:
(1) PAC regimen: CTX 400mg IV, Day 1
ADM 40mg IV, Day 2
DDP 80mg intraperitoneal, Day 3
(2) CFP regimen: CTX 400mg IV, Day 1
5FU 150mg intraperitoneal, Day 2
DDP 80mg intraperitoneal, Day 3
(3) CP regimen: CTX 200mg IV, Days 1–5
DDP 40mg IV drip, Days 1–5
(4) CHFP regimen: 5FU 1000mg IV drip, Day 1 or 8
DDP 40mg IV drip, Days 1 and 8
CTX 100mg PO twice daily, Days 2–7 and 9–16
2. Germ cell tumors and fleshy tumors often use:
(1) VAC regimen: VCR 2mg IV, Day 1
ACD 300μg IV drip, Days 2–6
CTX 300mg IV, Days 2–6
(2) FAC regimen: 5FU 1000mg IV drip, Days 1–5
ACD 300μg IV drip, Days 1–5
CTX 300mg IV, Days 1–5
(3) PVB regimen: VLB 20mg (or VCR 2mg) IV, Day 1
BLM 30mg IM or intraperitoneal, Day 2
DDP 20–30mg IV drip or intraperitoneal, Days 1–5
The above treatment regimens are generally administered at intervals of 3 to 4 weeks per course, with specific adjustments based on the patient's constitution, response level, blood profile, and liver and kidney functions. Medication should be administered for at least 4 to 6 courses. For advanced-stage or chemotherapy-resistant tumors, more courses are typically required—generally 8 to 10 courses in the first year, reducing to 3 to 4 courses in the second year.
(4) Radioimmunotherapy The radiosensitivity of malignant ovarian tumors varies greatly. Ovarian endodermal sinus tumors, immature teratomas, and embryonal carcinomas are the least sensitive, while grade II ovarian epithelial carcinomas and granulosa cell carcinomas are moderately sensitive. Dysgerminomas are the most sensitive and can often be controlled with postoperative radiotherapy. Since ovarian cancer tends to metastasize early to the abdominal cavity, the irradiation field should include both the abdominal and pelvic cavities. The liver and kidney areas should be shielded to avoid radiation injury. The total abdominal radiation dose ranges from 3000 cGY to 5000 cGY over 6 to 8 weeks.
Internal irradiation involves the intraperitoneal injection of colloidal gold (198Au) or phosphorus (32P), which can deliver a dose to the peritoneal surface that is difficult to achieve with external irradiation. Due to its limited penetration, it is used to treat superficial intraperitoneal metastases, microscopic residual tumors, or cases where stage I tumors rupture during surgery, thereby improving the five-year survival rate. A drawback is that the abdominal cavity must be free of adhesions to ensure uniform distribution of the radioactive isotopes; otherwise, intestinal injury may occur, leading to serious consequences. Typically, the dose for 198Au is 120–150 millicuries, and for 32P, it is 10–20 millicuries.
The prognosis of malignant ovarian tumors is related to clinical stage, pathological grade, tumor type, and treatment methods. The later the stage, the worse the outcome. According to follow-up statistics from 4,892 cases treated in 45 hospitals worldwide, the 5-year survival rate for stage Ia is 72%, stage IIa is 52%, stage III is 11%, and stage IV is 5%. For stage I cancers where the tumor is confined within the capsule, the 5-year survival rate can reach 90%. The poorer the differentiation of tumor cells, the worse the treatment outcome. Tumors with low malignant potential have significantly better treatment outcomes than epithelial carcinomas. Among ovarian cancers, embryonal carcinoma has the worst prognosis, while dysgerminoma has a favorable prognosis due to its sensitivity to radiation. Additionally, inadequate or inappropriate treatment can also adversely affect the outcome.
The focus is on early detection of tumors. Whether benign or malignant, early-stage patients often show no obvious symptoms, and benign tumors also have the potential for malignant transformation. Therefore, regular screenings should be conducted. To detect malignant tumor of the ovary early, the following points should be noted:
(1) All solid ovarian masses or cysts larger than 6cm should be surgically removed immediately.
(2) For women before menarche or after menopause, any ovarian mass should be considered a tumor. For women of childbearing age with small adnexal cystic masses, if no reduction is observed after 2 months, it should be considered a tumor. If the mass enlarges during observation, surgery should be performed promptly.
(3) For pelvic inflammatory masses, especially those suspected to be pelvic subcutaneous nodes or endometrial ectopic masses, if treatment is ineffective and a tumor cannot be ruled out, surgical exploration should be performed.
(4) If endometrial adenomatous hyperplasia or endometrial adenocarcinoma is detected after menopause, attention should be paid to whether there is an ovarian mass, and surgical treatment should be performed promptly.
(5) During pelvic surgery, both ovaries should be carefully examined for any abnormalities. Apart from the indications for ovarian disease Bingben itself, for patients aged 45 or older who require a hysterectomy due to uterine disease, bilateral adnexectomy is recommended.
