Ovarian Cancer — Symptoms, Causes & Treatment | MyMedicPlus

Ovarian cancer is the most lethal gynaecological malignancy and the fifth most common cause of cancer death in women — responsible for approximately 207,000 deaths annually from 314,000 new diagnoses worldwide each year. It encompasses a heterogeneous group of malignancies arising from different cell types in the ovary: epithelial ovarian cancers account for 90-95% of cases, with high-grade serous carcinoma (HGSC) being the most prevalent and aggressive histological subtype (70-80% of epithelial ovarian cancers), followed by endometrioid, clear cell, and mucinous carcinomas; germ cell tumours (3-5%, predominantly in young women), sex cord stromal tumours (2-4%), and borderline (low malignant potential) tumours. The central clinical challenge with ovarian cancer is that approximately 70-80% of women are diagnosed at Stage III or IV (after spread beyond the pelvis or to distant organs) — when survival rates are substantially lower — because early-stage disease is typically asymptomatic or produces only vague, non-specific symptoms. Five-year survival: Stage I — 92%; Stage II — 70%; Stage III — 29%; Stage IV — 13% (SEER database). Despite its late presentation, significant therapeutic advances have occurred: PARP inhibitors (olaparib, niraparib, rucaparib) have dramatically improved progression-free survival in BRCA-mutated and homologous recombination-deficient (HRD) ovarian cancer, and bevacizumab (anti-VEGF) provides additional benefit in high-risk Stage III-IV disease. High-grade serous carcinoma is now understood to originate predominantly from the fallopian tube fimbriae rather than the ovarian surface — leading to risk-reducing salpingo-oophorectomy protocols for high-risk women.

Ovarian cancer aetiology varies by histological subtype, but several unifying risk factors and genetic contributions are established. Genetic factors: BRCA1 germline mutations confer a 39-46% lifetime ovarian cancer risk; BRCA2 mutations 10-27%; Lynch syndrome (MLH1, MSH2, MSH6, PMS2 mutations — associated with endometrioid and clear cell ovarian cancer, as well as colorectal, endometrial, and gastric cancers); RAD51C and RAD51D mutations (5-7% lifetime risk). Together, hereditary ovarian cancer syndromes account for approximately 15-20% of all ovarian cancers. The remaining 80-85% are sporadic, arising from somatic mutations; molecular signatures of HGSC include near-universal TP53 mutation (96%), CCNE1 amplification, CDK12 mutation, and homologous recombination deficiency (HRD — broader category including BRCA1/2 and other HR pathway defects — present in 50% of HGSC and predicting platinum and PARP inhibitor sensitivity). Reproductive and hormonal risk factors: nulliparity (3x increased risk vs 5 or more pregnancies); early menarche and late menopause (longer cumulative ovulatory years — supporting the 'incessant ovulation' hypothesis that repeated ovulatory surface epithelial trauma drives malignant transformation); postmenopausal oestrogen-only HRT; endometriosis (3-4x risk of clear cell and endometrioid ovarian cancer, both arising from endometriotic cysts). Protective factors: oral contraceptive pill use (each year of OCP use reduces ovarian cancer risk by 5%, with 10 years of use reducing risk by 50% — this benefit persists for decades and forms the basis of chemoprevention in high-risk BRCA1/2 carriers); each completed pregnancy reduces risk by 10-15%; breastfeeding; tubal ligation; salpingectomy — bilateral salpingectomy at the time of other gynaecological surgery increasingly offered as opportunistic risk reduction (removes the fallopian tube fimbriae as the dominant site of HGSC origin). Modifiable risk factors: obesity (particularly postmenopausal obesity); talcum powder use (IARC Group 2B carcinogen when used in the genital area).

Ovarian cancer has long been characterised as a 'silent killer' — this is partially a myth, as symptoms are usually present but non-specific and easily attributed to other common conditions (IBS, menopausal symptoms, urinary urgency, bloating). The key is recognition that new persistent symptoms in a postmenopausal woman or a woman over 50 require investigation. Core symptom complex: persistent abdominal bloating or distension (present in 72% of ovarian cancer patients — particularly when persistent, recurring frequently, and not related to eating); pelvic or abdominal pain (69%); difficulty eating or early satiety (67%); and urinary urgency or frequency (frequent need to urinate — from bladder compression); these four symptoms, if occurring more than 12 times per month and new within the past year, have a sensitivity of 56.7% and specificity of 90% for ovarian cancer (Goff's symptom index). Additional symptoms: unexplained weight change (either gain from ascites or loss from reduced intake and cancer-associated cachexia); change in bowel habit; post-menopausal bleeding (more suggestive of endometrial cancer but may indicate ovarian endometrioid carcinoma); menstrual irregularity in premenopausal women; a palpable pelvic or abdominal mass. Presentation of advanced disease: ascites (abdominal distension, shifting dullness — from peritoneal carcinomatosis causing fluid accumulation); pleural effusion (dyspnoea, reduced breath sounds — particularly left-sided); bowel obstruction (constipation, vomiting, distension — from omental and bowel peritoneal deposits). Paraneoplastic syndromes: hypercalcaemia, Trousseau's sign (migratory thrombophlebitis), cerebellar degeneration (subacute cerebellar degeneration from anti-Yo antibodies — associated with Purkinje cell loss). Germ cell tumours (predominantly in young women aged 10-30 years) present with rapidly growing pelvic masses causing acute pain from torsion or rupture.

Ovarian cancer investigation begins with clinical assessment and imaging. Transvaginal ultrasound (TVS): the first-line investigation for suspected ovarian cancer — the IOTA ADNEX model integrates 6 ultrasound features (solid component size, number of papillary projections, presence of acoustic shadow, largest solid component diameter, irregular internal cyst wall, posterior acoustic enhancement) to calculate malignancy probability; IOTA simple rules and ADNEX model outperform clinical risk indices in international validation studies. Risk of Malignancy Index (RMI): combines serum CA-125 (U/mL) × menopausal status (1 if premenopausal, 3 if postmenopausal) × ultrasound score (1 point each for: multilocular cyst, solid areas, bilateral, ascites, intra-abdominal metastases); RMI above 200 has sensitivity 85% and specificity 97% for ovarian cancer — triggers urgent referral to a gynaecological oncology centre. Serum CA-125 (Cancer Antigen 125): elevated (above 35 U/mL) in 80% of advanced ovarian cancers but less reliable in early-stage disease; low specificity (elevated in endometriosis, fibroids, pelvic inflammatory disease, and other cancers); used in combination with TVS and IOTA/RMI. Additional biomarkers: HE4 (Human Epididymis Protein 4) — combined with CA-125 in the ROMA algorithm (Risk of Ovarian Malignancy Algorithm) improves sensitivity for HGSC; AFP and hCG for germ cell tumours (dysgerminoma, yolk sac tumour); inhibin A and B for granulosa cell tumours; LDH for dysgerminoma. CT of chest, abdomen, and pelvis: staging assessment of peritoneal disease extent, lymph node involvement, liver and lung metastases, and pleural effusion — mandatory before surgery. PET-CT for equivocal CT findings. Definitive tissue diagnosis: surgical staging (total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node sampling, peritoneal biopsies) — the gold standard; image-guided CT biopsy (peritoneal deposits or omental biopsy) when upfront surgery is not feasible (for neoadjuvant chemotherapy planning). Germline BRCA1/2 testing: offered to all women with newly diagnosed high-grade serous, endometrioid, clear cell, or undifferentiated ovarian cancer (NICE guideline — positive result guides PARP inhibitor maintenance therapy and enables family cascade testing). Somatic tumour testing for HRD status (Foundation Medicine, Myriad myChoice CDx).

Treatment for advanced ovarian cancer is complex and requires a specialised gynaecological oncology multidisciplinary team. Surgery: optimal cytoreductive surgery (debulking) is the cornerstone of ovarian cancer treatment — removing all visible tumour (complete resection, R0 — no macroscopic residual disease) is the single most important determinant of survival (complete cytoreduction improves median overall survival by 12-17 months compared to suboptimal debulking). Primary debulking surgery (PDS) — upfront surgery — is performed when the patient is medically fit and CT assessment suggests complete cytoreduction is achievable; procedure includes total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissection, and resection of all peritoneal deposits including diaphragmatic stripping, bowel resection, and splenectomy where necessary. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS): preferred for patients unsuitable for upfront complete cytoreduction (high disease burden, medical comorbidity) — 3-4 cycles of carboplatin + paclitaxel before surgery, followed by IDS, then 3 further cycles; outcomes equivalent to PDS in patients where complete cytoreduction is not achievable upfront (CHORUS and EORTC 55971 trials). Chemotherapy: platinum-based combination chemotherapy is the standard systemic treatment — carboplatin (AUC5-6) plus paclitaxel (175mg/m² q21 days for 6 cycles) achieves response rates of 70-80% but relapse is near-universal in Stage III-IV; the addition of bevacizumab (anti-VEGF antibody — 15mg/kg q21 days concurrently with and then 12 months maintenance) extends PFS by 4 months in high-risk patients (ICON7, GOG218 trials). PARP inhibitor maintenance therapy — the most significant therapeutic advance in ovarian cancer treatment: olaparib (Lynparza — 300mg BD), niraparib (Zejula — 200-300mg daily), or rucaparib (Rubraca) given as maintenance after complete or partial response to platinum chemotherapy; PARP inhibitors are most effective in BRCA1/2 mutated and HRD-positive tumours — SOLO-1 trial: olaparib maintenance in BRCA-mutated Stage III-IV achieved 5-year PFS rate of 48% vs 21% for placebo; PRIMA trial: niraparib maintenance in HRD-positive patients achieved 2-year PFS of 62% vs 19% for placebo; PAOLA-1 trial: olaparib plus bevacizumab maintenance in HRD-positive patients. Recurrent ovarian cancer: platinum-sensitive relapse (above 6 months after last platinum) — rechallenge with platinum doublet plus PARP inhibitor maintenance if not previously used; platinum-resistant relapse (below 6 months) — single-agent chemotherapy (gemcitabine, pegylated liposomal doxorubicin, topotecan) or clinical trial. Fertility-sparing surgery for Stage IA Grade 1 epithelial tumours and all germ cell and borderline tumours in young women.

Bowel obstruction from peritoneal carcinomatosis is one of the most distressing and common complications of advanced ovarian cancer — causing abdominal distension, vomiting, obstipation, and severe pain; management ranges from conservative (nasogastric decompression, TPN) to palliative surgery (defunctioning stoma, bypass) or self-expanding metal stent; requires expert palliative care involvement when surgical options are exhausted. Malignant ascites from peritoneal carcinomatosis accumulates rapidly (litres per week), causing severe abdominal distension, dyspnoea (diaphragm elevation), and discomfort; managed with regular therapeutic paracentesis (draining 2-4 litres at a time), long-term peritoneal drainage catheters (PleurX), or bevacizumab which significantly reduces ascites accumulation. Pleural effusion (particularly left-sided) causes progressive dyspnoea and requires thoracentesis or indwelling pleural catheter (IPC) for palliation. Venous thromboembolism (VTE — DVT and PE) is a major cause of morbidity and mortality in ovarian cancer: cancer itself and surgical treatment create a hypercoagulable state; all ovarian cancer patients on chemotherapy should receive LMWH (dalteparin, tinzaparin) thromboprophylaxis for 4 weeks post-surgery and consider LMWH for 6+ months in high-risk metastatic disease. Chemotherapy toxicities: peripheral neuropathy (cumulative carboplatin and paclitaxel toxicity — sensory neuropathy, impairing fine motor tasks and causing falls risk); myelosuppression (anaemia, thrombocytopenia, neutropenia — risk of febrile neutropenia requiring G-CSF prophylaxis and inpatient treatment); alopecia; nausea; fatigue. PARP inhibitor toxicities: nausea (managed with antiemetics), anaemia, thrombocytopenia, secondary myelodysplastic syndrome/AML (rare — below 2%). Ovarian insufficiency from bilateral oophorectomy in premenopausal women causes immediate surgical menopause — hot flushes, dyspareunia, reduced libido, osteoporosis risk — managed with HRT (use of HRT after ovarian cancer surgery does not worsen outcomes in non-hormone-sensitive tumours).

Risk reduction for high-risk women (BRCA1/2 mutation carriers): risk-reducing salpingo-oophorectomy (RRSO) is the most effective intervention — reduces ovarian cancer risk by 80% and overall cancer mortality in BRCA1/2 carriers; recommended at age 35-40 for BRCA1 carriers (after completion of childbearing) and 40-45 for BRCA2 carriers; removes the fallopian tubes (primary site of HGSC precursors — STIC lesions, or serous tubal intraepithelial carcinoma) and ovaries; causes immediate surgical menopause — HRT is safe and recommended until natural menopausal age to manage menopausal symptoms and prevent osteoporosis. Combined oral contraceptive pill (OCP): 10 years of OCP use reduces ovarian cancer risk by 50% — even in BRCA1/2 carriers (risk reduction approximately 50% in BRCA2 carriers; data in BRCA1 carriers more complex due to breast cancer risk concerns); OCP use is a key component of chemoprevention strategy for women delaying or declining RRSO. Opportunistic risk-reducing bilateral salpingectomy: bilateral salpingectomy at the time of other gynaecological surgery (hysterectomy, caesarean section) is offered to all women as an opportunity to reduce future ovarian cancer risk by removing the precursor site; salpingectomy alone (without oophorectomy) avoids surgical menopause and is an increasingly accepted option for intermediate-risk women. Population screening: the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS — involving 202,000 women) did not demonstrate a reduction in ovarian cancer mortality from annual multimodal screening (CA-125 Risk of Ovarian Cancer Algorithm [ROCA] plus TVS), despite detecting cancers at earlier stages; routine population screening is not currently recommended. Genetic testing and cascade testing: all women diagnosed with ovarian cancer should receive germline BRCA1/2 and broader panel genetic testing — positive results trigger cascade testing of all first-degree relatives (50% chance of sharing the mutation) and access to risk-reducing interventions. Surveillance for high-risk women declining RRSO: 6-monthly TVS plus CA-125 is offered as surveillance, with the caveat that its mortality benefit is unproven.

See your GP promptly (ideally within 1-2 weeks) for: persistent or frequently recurring bloating, abdominal distension, pelvic or lower abdominal pain, difficulty eating or early satiety, or urinary urgency — particularly if these symptoms are new, occurring more than 12 times per month, and not explained by another condition; any palpable abdominal or pelvic mass; unexplained weight loss with abdominal symptoms; post-menopausal vaginal bleeding (may also indicate ovarian or endometrial cancer). Do not dismiss persistent abdominal symptoms as irritable bowel syndrome, menopausal bloating, or 'just ageing' without gynaecological assessment and measurement of CA-125 and pelvic ultrasound — early referral to gynaecology or gynaecological oncology is essential. Seek urgent emergency assessment for: sudden severe abdominal or pelvic pain (possible ovarian cyst torsion, rupture, or acute presentation of a rapidly growing ovarian mass — germ cell tumours can grow very rapidly in young women); acute bowel obstruction symptoms (complete constipation, vomiting, gross distension). If you have a known BRCA1/2 mutation or a strong family history of ovarian and breast cancer (3 or more relatives): see your GP or a hereditary cancer clinic for referral to genetic counselling and discussion of risk-reducing salpingo-oophorectomy timing — the most effective ovarian cancer prevention available for high-risk women.