Ovarian Cancer Management

Last updated: 01 August 2025
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Evaluation

Risk of Malignancy Index (RMI)  

The risk of malignancy index is used in women with suspected ovarian cancer to help guide the management of the patient. This index is the product of serum CA-125, menopausal status, and ultrasound score of the patient.  

It is simple to use but is negatively affected in the premenopausal age due to the high incidence of increased CA-125 levels in this age group which may be secondary to endometriomas, borderline ovarian tumors, or non-epithelial ovarian tumors.  

Staging  

Staging determines the extent of cancer upon diagnosis. It is an important factor in the choice of treatment and may also predict prognosis.  

International Federation of Gynecology and Obstetrics (FIGO) Ovarian Cancer Staging System  

The International Federation of Gynecology and Obstetrics (FIGO) developed the FIGO ovarian cancer staging system.  

Stage I (T1)  

Stage I (T1) is when the tumor is limited to the ovaries or fallopian tube(s), no regional lymph node (LN) metastasis or distant organ metastasis.  

Stage IA (T1a)  

Stage IA (T1a) is when the tumor is limited to one ovary with an intact capsule or fallopian tube, no tumor on the ovarian or fallopian tube surface, no malignant cells in ascites or peritoneal washings, no regional lymph node metastasis or distant organ metastasis.  

Stage IB (T1b)  

Stage IB (T1B) is when the tumor involves both ovaries with an intact capsule or fallopian tubes, no tumor on the ovarian or fallopian tube surface, no malignant cells in ascites or peritoneal washings, no regional lymph node metastasis or distant organ metastasis.  

Stage IC  

Stage IC is when the tumor is limited to one or both ovaries or fallopian tubes, with any of the following:

  • Stage IC1 (T1c1): Surgical spill
  • Stage IC2 (T1c2): Presence of tumor on ovarian or fallopian tube surface or capsule
  • Stage IC3 (T1c3): Presence of malignant cells in ascites or peritoneal washings 



Stage II (T2)  

Stage II (T2) is when the tumor is in one or both ovaries or fallopian tubes with pelvic extension (below the pelvic brim) or primary peritoneal cancer.  

Stage IIA (T2a)  

Stage IIA (T2a) is when there is tumor extension and/or implants on the uterus and/or ovaries and/or fallopian tubes.  

Stage IIB (T2b)  

Stage IIB (T2B) is when there is tumor extension to other pelvic intraperitoneal (IP) tissues.  

Stage III (T1/T2-N1; T3-N1)  

Stage III is when the tumor is in one or both ovaries or fallopian tubes, or primary peritoneal cancer, with histologically or cytologically confirmed peritoneal metastasis outside the pelvis, and/or retroperitoneal lymph node metastasis.  

Stage IIIA1 (T1/T2-N1)  

Stage IIIA1 is when there is positive retroperitoneal lymph nodes only: IIIA1(i) (N1a) Metastasis ≤10 mm; IIIA1(ii) (N1b) Metastasis >10 mm  

Stage IIIA2 (T3a2-N0/N1)  

Stage IIIA2 is when there is microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes.  

Stage IIIB (T3b-N0/N1)  

Stage IIIB is when there is macroscopic peritoneal metastasis outside the pelvis that is ≤2 cm with or without retroperitoneal lymph node metastasis.    

Stage IIIC (T3c-N0/N1)  

Stage IIIC is when there is macroscopic peritoneal metastasis outside the pelvis that is >2 cm with or without retroperitoneal lymph node metastasis; this includes an extension to the capsule of the liver and spleen.    

Stage IV (Any T, Any N, M1)  

Stage IV involves distant metastasis, not including peritoneal metastases.  

Stage IVA (M1a)  

Stage IVA is when there is pleural effusion with positive cytology.  

Stage IVB (M1b)  

Stabe IVB is when there is parenchymal metastases, metastases to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of the abdominal cavity); transmural involvement of the intestine. 


Ovarian Cancer_ManagementOvarian Cancer_Management

Pharmacological therapy

Systemic Therapy

Neoadjuvant Chemotherapy for Epithelial Ovarian Carcinoma  

Neoadjuvant chemotherapy should be considered in patients with advanced-stage ovarian cancer who are not good candidates for upfront primary debulking surgery due to advanced age, frailty, poor performance status, comorbidities, or who have diseases unlikely to be optimally cytoreduced. The recommended neoadjuvant chemotherapy regimens include Paclitaxel/Carboplatin, dose-dense Paclitaxel/Carboplatin, Docetaxel/Carboplatin, Carboplatin/pegylated liposomal Doxorubicin and Paclitaxel/Carboplatin/ Bevacizumab. Regimens that include Bevacizumab should be used with caution before interval debulking surgery (IDS) due to its effect on postoperative healing. Bevacizumab if used as part of neoadjuvant therapy should be withheld for at least 6 weeks before interval debulking surgery.  

Hyperthermic IP chemotherapy (HIPEC) may be considered in patients with stage III disease being given neoadjuvant therapy at the time of interval debulking surgery, in patients with stage IV disease with favorable response to IP and extraperitoneal neoadjuvant therapy, or in whom stage IV disease sites have completely resolved (eg resolution of malignant pleural effusion) or are now deemed resectable. A procedure wherein chemotherapy is administered in a heated solution perfused throughout the peritoneal space resulting in increased penetration of chemotherapy at the peritoneal surface & enhanced sensitivity of cancer cells to chemotherapy. It is an option for stage III patients with a response or stable disease after three cycles of neoadjuvant therapy. The recommended agent for HIPEC is Cisplatin. 

Systemic Therapy for Epithelial Ovarian Carcinoma  

Most patients should receive postoperative systemic chemotherapy. After surgical cytoreduction, platinum-based chemotherapy is the treatment of choice for patients with advanced epithelial ovarian cancer which is initiated within 6 weeks after surgery. Monotherapy with Carboplatin every 3 weeks for six cycles as adjuvant therapy can be given in early-stage epithelial ovarian cancer; Cisplatin may be an alternative to Carboplatin. Recommendations for the number of cycles of treatment vary with the stage of the disease; earlier stage disease (stage I) is given 3 to 6 cycles while advanced stages (II-IV) are given in 6 cycles.  

Recommended Primary Therapy Regimens for Stage I Disease

For stage 1 disease, the preferred regimens include the following:

  • Paclitaxel/Carboplatin
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma, stage IA, IB, and IC, grades 1-3 and low-grade serous (stage IC) or grade 1 endometroid stage (stage IC)
    • With maintenance Letrozole or other hormonal therapy (eg Anastrozole, Exemestane, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous (stage IC) or grade 1 endometroid (stage IC)
  • Fluorouracil (5-FU)/Leucovorin/Oxaliplatin: Mucinous carcinoma stage IA, IB, and IC, grades 1-3 
  • Capecitabine/Oxaliplatin: Mucinous carcinoma stage IA, IB, and IC, grades 1-3
  • Hormone therapy (eg Anastrozole, Letrozole, Exemestane): Low-grade serous (stage IC) or grade I endometrioid (stage IC)

Other recommended regimens include the following:

  • Carboplatin/liposomal Doxorubicin
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma, stage IA, IB, and IC, grades 1-3 and low-grade serous (stage IC) or grade 1 endometroid stage (stage IC)
    • With maintenance Letrozole or other hormonal therapy (eg Anastrozole, Exemestane, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous (stage IC) or grade 1 endometroid (stage IC)
  • Docetaxel/Carboplatin
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma, stage IA, IB, and IC, grades 1-3 and low-grade serous (stage IC) or grade 1 endometroid stage (stage IC)
    • With maintenance Letrozole or other hormonal therapy (eg Anastrozole, Exemestane, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous (stage IC) or grade 1 endometroid (stage IC)
  • Hormone therapy (eg Fulvestrant, Goserelin Leuprolide acetate, Tamoxifen): Low-grade serous (stage IC) or grade I endometrioid (stage IC)

Conditional regimens include the following:

  • Carboplatin or Cisplatin or Paclitaxel plus Ifosfamide: For carcinosarcoma
  • Paclitaxel/Cisplatin: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma, stage IA, IB, and IC, grades 1-3 and low-grade serous (stage IC) or grade 1 endometroid stage (stage IC)



Recommended Primary Therapy Regimens for Stage II-IV Disease

For stage II-IV disease, the preferred regimens include the following:

  • Paclitaxel/Carboplatin: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma and low-grade serous or grade 1 endometroid
  • Paclitaxel/Carboplatin/Bevacizumab plus maintenance Bevacizumab
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma and low-grade serous or grade 1 endometroid 
    • Maintenance with Bevacizumab monotherapy is recommended only for patients who have not progressed during the 6 cycles of upfront Paclitaxel/Carboplatin/Bevacizumab therapy
  • 5-FU/Leucovorin/Oxaliplatin with or without Bevacizumab: Mucinous carcinoma
  • Capecitabine/Oxaliplatin with or without Bevacizumab: Mucinous carcinoma
  • Paclitaxel/Carboplatin with maintenance Letrozole or other hormone therapy (aromatase inhibitors, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous or grade I endometrioid 
  • Hormone therapy (eg Anastrozole, Letrozole, Exemestane): Low-grade serous or grade I endometrioid

Other recommended regimens include the following:

  • Weekly Paclitaxel/weekly Carboplatin: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma and low-grade serous or grade 1 endometroid
  • Docetaxel/Carboplatin
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, and mucinous carcinoma
    • With maintenance Letrozole or other hormonal therapy (eg aromatase inhibitors, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous or grade I endometroid
  • Carboplatin/liposomal Doxorubicin
    • High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, and mucinous carcinoma
    • With maintenance Letrozole or other hormonal therapy (eg aromatase inhibitors, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous or grade I endometroid
  • Weekly Paclitaxel/3-weekly Carboplatin: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma and low-grade serous or grade 1 endometroid
  • Docetaxel/Carboplatin/Bevacizumab plus maintenance Bevacizumab: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma, mucinous carcinoma and low-grade serous or grade 1 endometroid
  • Hormone therapy (eg Fulvestrant, Goserelin acetate, Leuprolide acetate, Tamoxifen): Low-grade serous or grade I endometrioid 

Conditional regimens include the following:

  • Paclitaxel/Cisplatin
  • Docetaxel/Oxaliplatin/Bevacizumab plus maintenance Bevacizumab
  • IP or IV Paclitaxel/Cisplatin: For optimally-debulked high-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma stage II to III
  • IP or IV Paclitaxel/Carboplatin: High-grade serous, endometroid (grade 2/3), clear cell carcinoma, carcinosarcoma
  • Carboplatin or Cisplatin or Paclitaxel plus Ifosfamide: For carcinosarcoma



Recommended Intravenous (IV) Regimens

The recommended IV regimens have different toxicity profiles and they are the following:

  • Paclitaxel followed by Carboplatin given every 3 weeks for 3-6 cycles (preferred regimen)
  • Paclitaxel followed by Carboplatin weekly for 18 weeks 
  • Paclitaxel followed by Cisplatin given every 3 weeks for 3-9 cycles 
  • Dose-dense Paclitaxel on days 1, 8, and 15 plus Carboplatin on day 1 every 3 weeks for 6 cycles
  • Paclitaxel plus Carboplatin given every 3 weeks for 3-6 cycles for patients >70 years old and/or those with comorbidities
  • Paclitaxel followed by Carboplatin on days 1, 8, and 15 given every 3 weeks for 6 cycles for patients >70 years old and/or those with comorbidities
  • Docetaxel followed by Carboplatin given every 3 weeks for 3-6 cycles 
  • Carboplatin plus pegylated liposomal Doxorubicin every 4 weeks for 3-6 cycles
  • Paclitaxel followed by Carboplatin and Bevacizumab every 3 weeks for 5-6 cycles
    • Continue Bevacizumab for up to 12 additional cycles
  • Paclitaxel followed by Carboplatin every 3 weeks for 6 cycles; add Bevacizumab starting cycle 2
    • Continue Bevacizumab up to 22 cycles
  • Docetaxel followed by Oxaliplatin and Bevacizumab every 3 weeks for 6 cycles
    • Continue Bevacizumab every 3 weeks to complete 1 year of therapy
  • Docetaxel followed by Carboplatin every 3 weeks for 6 cycles; add Bevacizumab starting cycle 2
    • Continue Bevacizumab up to 22 cycles



IP Systemic Therapy  

IP systemic therapy allows the possibility of targeting therapy to the site of the disease while minimizing systemic toxicities. It is recommended for all stage III patients with optimally debulked (<1 cm residual) disease. Optimally debulked stage II patients may also receive IP chemotherapy.  

The recommended regimens include Cisplatin on day 2 after IV Paclitaxel on day 1, then IP Paclitaxel on day 8, every 3 weeks for 6 cycles, and IP Carboplatin given with IV Paclitaxel on day 1, then IV Paclitaxel on days 8 and 15, every 3 weeks for 6-8 cycles. IP Carboplatin given with IV Paclitaxel on day 1, followed by IP Paclitaxel on day 8 is a treatment option for patients who received neoadjuvant chemotherapy and interval debulking agent.  

Women unable to complete IP therapy should receive IV therapy. Catheter complications, nausea, vomiting, dehydration, or abdominal pain are common reasons for discontinuing IP treatment.  

Borderline Epithelial Ovarian Carcinoma  

The additional chemotherapeutic option is hormone therapy including aromatase inhibitors (Anastrozole, Letrozole), Leuprolide, and Tamoxifen.    

Maintenance Therapy for Stage II-IV Post-primary Treatment  

The recommended treatment options depend on the disease stage, primary systemic therapy agents used, primary treatment response, and BRCA1/2 mutation status. 

Patients without Bevacizumab during primary treatment: 

  • With BRCA1/2 wild-type or unknown mutation with complete or partial response: Niraparib or Rucaparib 
  • With germline or somatic BRCA1/2 mutation with complete or partial response: Olaparib or Niraparib or Rucaparib

Patients with Bevacizumab as part of primary treatment:

  • With BRCA1/2 wild-type or unknown mutation with complete or partial response
    • HR proficient or unknown status: Bevacizumab 
    • HR deficient: with or without Olaparib or Niraparib
  • With germline or somatic BRCA1/2 mutation with complete or partial response: Bevacizumab with Olaparib or Niraparib or monotherapy with Olaparib or Niraparib or Rucaparib



Systemic Therapy for Germ Cell Ovarian Carcinoma  

Patients with embryonal or endodermal sinus tumors, stage II-IV dysgerminoma or stage I, grade 2-3, or stage II-IV immature teratoma should receive postoperative chemotherapy with Bleomycin/Etoposide/Cisplatin for 3-4 cycles.  

In some patients with stage II-III dysgerminoma for whom minimizing toxicity is critical, three courses of Etoposide/Carboplatin combination can be used: Carboplatin on day 1 plus Etoposide on days 1-3 every 4 weeks for 3 cycles.  

Systemic Therapy for Sex Cord-Stromal Ovarian Carcinoma  

For patients with stage II-IV tumors, Paclitaxel/Carboplatin regimen is preferred. Etoposide/Cisplatin is another recommended regimen and Bleomycin/Etoposide/Cisplatin regimen may be useful in certain circumstances.  

Platinum-based chemotherapy should be considered for patients with high-risk stage 1 tumors (stage IC, poorly differentiated tumor, tumor size >10 to 15 cm, tumor rupture). Patients with limited stage II-IV tumors should undergo radiotherapy.  

Recurrence Therapy for Epithelial Ovarian Carcinoma

Cytotoxic Therapy

Combination platinum-based chemotherapy may be given and are as follows: 

  • Preferred for first recurrence in platinum-sensitive patients (ie patients who relapse ≥6 months after initial chemotherapy)
  • The decision regarding which combination to use should be based on the toxicity experienced with primary therapy, patient preference, and other factors
  • Preferred agents for platinum-sensitive disease include the following:
    • Carboplatin/Paclitaxel with or without Bevacizumab
    • Carboplatin/Gemcitabine with or without Bevacizumab
    • Carboplatin/liposomal Doxorubicin with or without Bevacizumab
    • Cisplatin/Gemcitabine
  • Other recommended regimens for platinum-sensitive disease include Capecitabine, Carboplatin, Carboplatin/Docetaxel, Carboplatin/Paclitaxel weekly combination, Cisplatin, Cyclophosphamide, Doxorubicin, Ifosfamide, Irinotecan, Melphalan, Oxaliplatin, Paclitaxel, albumin-bound Paclitaxel, Pemetrexed and Vinorelbine


The preferred non-platinum-based agents for platinum-resistant disease include:

  • Docetaxel
  • Oral Etoposide 
  • Gemcitabine
  • Liposomal Doxorubicin
  • Weekly Paclitaxel
  • Topotecan
  • Topotecan/Bevacizumab
  • Trabectedin/pegylated liposomal Doxorubicin: Approved in Europe for patients relapsing >6 months after last platinum therapy
  • Weekly Paclitaxel/Bevacizumab
  • Liposomal Doxorubicin/Bevacizumab
  • Oral Cyclophosphamide/Bevacizumab 



Other recommended regimens for platinum-resistant disease include Capecitabine, Carboplatin/Docetaxel, Carboplatin/Paclitaxel weekly combination, Carboplatin/Gemcitabine with or without Bevacizumab, Carboplatin/liposomal Doxorubicin with or without Bevacizumab, Carboplatin/Paclitaxel with or without Bevacizumab, Cyclophosphamide, Doxorubicin, Gemcitabine/Bevacizumab, Gemcitabine/Cisplatin, Ifosfamide, Irinotecan, Ixabepilone/Bevacizumab, Melphalan, oral Cyclophosphamide/Pembrolizumab/Bevacizumab, Oxaliplatin, Paclitaxel, albumin-bound Paclitaxel, Pemetrexed, Sorafenib/Topotecan and Vinorelbine.

Targeted Therapy  

Bevacizumab is the preferred agent for platinum-sensitive recurrent disease. Preferred agents for platinum-resistant disease include Bevacizumab and Mirvetuximab. In the case of Bevacizumab, it is also the preferred agent which was shown to slow down the growth of advanced ovarian cancer. It is recommended for patients with platinum-resistant recurrent disease with a history of ≤2 prior chemotherapy regimens, to be given in combination with Paclitaxel, pegylated liposomal Doxorubicin or Topotecan. It may be used as maintenance therapy in patients with stage II-IV disease with wild-type or unknown BRCA1/2 mutation who were responsive to initial recurrence chemotherapy until disease progression or unacceptable toxicity. Mirvetuximab soravtansine-gynx is preferred for patients with folate receptor-alpha (FRα)-expressing tumors (≥75% positive tumors).  

Other recommended regimens for recurrent ovarian cancer include Niraparib with or without Bevacizumab, Olaparib, Pazopanib, and Rucaparib. Olaparib may be given to patients with advanced ovarian cancer with deleterious germline BRCA mutation with complete or partial response after ≥2 lines of chemotherapy. Niraparib may be given to patients with homologous recombination (HR) status-positive advanced ovarian cancer for those who have undergone treatment with ≥3 lines of chemotherapy. Rucaparib may be given to patients with advanced ovarian cancer with deleterious germline and/or somatic BRCA mutation who have undergone treatment with ≥2 lines of chemotherapy. Niraparib with Bevacizumab may be given to patients with platinum-sensitive recurrent disease.  

PARP inhibitors Olaparib, Niraparib, and Rucaparib are maintenance therapy options for patients with recurrent disease with complete or partial response to platinum-based chemotherapy. Niraparib or Rucaparib maintenance therapy is an option for patients with wild-type or unknown BRCA1/2 mutation.

Hormone Therapy  

Hormonal therapy that may be considered for platinum-sensitive and platinum-resistant disease includes aromatase inhibitors (eg Anastrozole, Exemestane, Letrozole), Goserelin acetate, Leuprolide acetate, Megestrol acetate, and Tamoxifen. In the case of Tamoxifen, it is not recommended for low-grade serous carcinoma. Fulvestrant may be considered for platinum-sensitive and platinum-resistant low-grade serous carcinoma.

Other Agents to be Considered in Certain Circumstances  
 
For platinum-sensitive and platinum-resistant disease, therapeutic options include:

  • BRAF V600E-positive tumors: Dabrafenib plus Tramatenib
  • NTRK gene fusion-positive carcinoma: Entrectinib, Larotrectinib or Repotrectinib
  • Confirmed taxane hypersensitivity: Carboplatin/albumin-bound Paclitaxel
  • Low-grade serous carcinoma: Avutometinib/Defactinib (for KRAS-mutated tumors), Binimetinib, Trametinib
  • Microsatellite instability-high (MSI-H) or mismatch, repair-deficient (dMMR) solid tumors or patients with tumor mutational burden-high (TMB-H) tumors ≥10 mutations/megabase: Pembrolizumab
  • MSI-H/dMMR recurrent or advanced tumors: Dostarlimab-gxly
  • RET gene fusion-positive tumors: Selpercatinib
  • For patients >70 years of age: Carboplatin/Paclitaxel 



For platinum-sensitive disease only, therapeutic options include:

  • Mucinous carcinoma: 5-FU/Leucovorin/Oxaliplatin with or without Bevacizumab and Capecitabine/Oxaliplatin with or without Bevacizumab
  • Clear cell carcinoma: Irinotecan/Cisplatin
  • FRα-expressing tumors (≥75% positive tumor cells): Mirvetuximab soravtansine-gynx
  • FRα-expressing tumors (≥50% positive tumor cells): Mirvetuximab soravtansine-gynx/Bevacizumab
  • HER2-positive tumors (IHC3+ or 2+): Fam-trastuzumab deruxetecan-nxki


For platinum-resistant disease only, therapeutic options include:

  • FRα-expressing tumors (≥25% positive tumor cells): Mirvetuximab soravtansine-gynx/Bevacizumab
  • Mucinous carcinoma: Folinic acid (Leucovorin, Calcium folinate), 5-FU, and Irinotecan (FOLFIRI) with or without Bevacizumab



Recurrence Therapy for Germ Cell Ovarian Carcinoma  

Recurrence therapy is recommended in patients with recurrent or residual disease after multiple chemotherapeutic regimens for whom no curative options are considered possible. The preferred options which are potentially curative regimens are high-dose chemotherapy plus hematopoietic cell transplant (HCT) or Paclitaxel/Ifosfamide/ Cisplatin (TIP).  

Other recommended options which are for palliation only may include Vincristine/Dactinomycin/ Cyclophosphamide (VAC), Vinblastine/Ifosfamide/Cisplatin (VeIP), Etoposide/Ifosfamide/Cisplatin (VIP), Cisplatin/Etoposide (if not previously used), Docetaxel/Carboplatin, Gemcitabine/Paclitaxel/Oxaliplatin, Gemcitabine/Oxaliplatin, Paclitaxel/Carboplatin, Paclitaxel/Gemcitabine, Paclitaxel/Ifosfamide, Pembrolizumab (if with MSI-H/dMMR or TMB-H), oral Etoposide, Docetaxel, Paclitaxel, radiation therapy, or supportive care. Combination chemotherapy is not recommended in patients with recurrent or residual disease who have no curative options. Ifosfamide/platinum-based chemotherapy with or without Paclitaxel should be considered as a second-line option for patients with platinum-sensitive relapsed disease whose progression occurred >4-6 weeks after completion of primary therapy.  

Recurrence Therapy for Sex Cord-Stromal Ovarian Carcinoma  

For recurrence therapy for sex cord-stromal ovarian carcinoma, the preferred regimen is Paclitaxel/Carboplatin. Other recommended regimens include Bevacizumab, Docetaxel, Etoposide/Cisplatin (if not previously used), Paclitaxel, Paclitaxel/Ifosfamide or supportive care. 

Other regimens which may be useful in certain circumstances include: 

  • Bleomycin/Etoposide/Cisplatin (if not previously used)
  • Aromatase inhibitors (eg Anastrozole, Exemestane, Letrozole)
  • Goserelin acetate or Leuprolide acetate may be used for granulosa cell tumors 
  • Tamoxifen
  • VAC 

Nonpharmacological

Observation

Postoperative observation is an option for patients with confirmed stage IA/B disease. Studies have shown that select patients with stage I ovarian cancer have >90% survival with surgical treatment alone and there are no proven clinical benefits from adjuvant chemotherapy for those who have had complete surgical staging for low-risk disease in certain cancer types. It should only be considered in patients who have had resection of all diseases and complete surgical staging to rule out the possibility of clinically occult disease that would result in upstaging.  

Observation may be an option for those with less common epithelial cancer types (eg mucinous, clear cell, grade 1 endometrioid, low-grade serous) wherein adjuvant systemic therapy has shown no benefit. It may be a maintenance option for patients with stage II disease without Bevacizumab during primary treatment and with germline or somatic BRCA1/2 mutation or wild-type or unknown mutation with complete response. 

Surgery

Surgery for Epithelial Ovarian Carcinoma  

The primary treatment for presumed ovarian cancer consists of appropriate surgical staging and cytoreduction followed by systemic chemotherapy in most patients.  

Initial surgery should be a comprehensive staging laparotomy, including a total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). It is recommended for patients with stage IA-IV ovarian cancer if optimal cytoreduction is feasible, fertility is not a concern, and the patient is a surgical candidate. Laparotomy is the standard surgical option in treating and staging patients with apparent early-stage ovarian carcinoma. Minimally invasive techniques may be an option in early-stage disease to achieve surgical goals in selected patients if performed by an experienced gynecologic surgeon.  

Omentectomy, peritoneal washing, peritoneal biopsies, evaluation of the entire abdominal cavity, and retroperitoneal assessment that involves both the pelvic and para-aortic areas should be performed. For patients who wish to maintain their fertility, unilateral salpingo-oophorectomy (USO) or bilateral salphingo-oophorectomy may be adequate for young patients with stage IA and IB tumors, respectively and/or low-risk tumors (ie early stage, low-grade invasive tumors, low malignant-potential lesions, malignant germ cell or sex cord-stromal tumors).  

Cytoreductive or Debulking Surgery  

Cytoreductive or debulking surgery is the initial treatment recommendation for patients with clinical stage II, III, or IV disease. It is recommended for all patients with stage II to IV diseases with potentially resectable residual disease. It is an optimal treatment if the residual tumor nodules are <1 cm in maximum diameter or thickness.  

Extensive resection of upper abdominal ovarian metastases is recommended for patients who can tolerate this surgery. Procedures that may be considered for optimal surgical cytoreduction (in all stages) include bowel resection, diaphragm or other peritoneal surface stripping, splenectomy, partial hepatectomy, cholecystectomy, partial gastrectomy, or cystectomy, ureteroneocystostomy, distal pancreatectomy, or appendectomy.  

Secondary Cytoreduction  

Secondary cytoreduction is considered in patients with recurrent ovarian cancer who recur >6 months since completion of primary chemotherapy, with good performance status, do not have ascites, and have limited foci of disease amenable to complete resection.  

Interval Debulking Surgery (IDS)   

Interval debulking surgery should include completion hysterectomy and salpingo-oophorectomy with comprehensive staging. It should be performed in patients responsive to three to four cycles of neoadjuvant chemotherapy or in patients with stable disease. Evaluation for potential interval debulking surgery should be done after three to four cycles of neoadjuvant chemotherapy. Interval debulking surgery with completion hysterectomy with bilateral salphingo-oophorectomy and cytoreduction should be performed in patients responsive to neoadjuvant therapy.  

Patients with stable disease after 3-4 cycles of neoadjuvant therapy may consider interval debulking surgery with completion hysterectomy with bilateral salpingo-oophorectomy and cytoreduction or switching to persistent or recurrent disease treatment or treatment with additional cycles of neoadjuvant chemotherapy to a total of ≥6 cycles followed by reassessment to determine if interval debulking surgery can be performed or to switch to recurrent or persistent disease treatment.  

Interval debulking surgery should be followed with at least 3 additional cycles of the same chemotherapy regimen. It may be done through minimally invasive procedures in select patients provided that optimal debulking can be achieved. 


Ancillary Palliative Surgery  

Ancillary palliative surgery may be suitable in select patients and include thoracentesis, pleurodesis, video-assisted thoracoscopy or insertion of a pleural catheter, paracentesis or insertion of indwelling peritoneal catheter, nephrostomy or use of ureteral stents, gastrostomy tube, intestinal stents or surgical relief of intestinal obstruction.  

Surgery for Malignant Germ Cell Tumors  

Completion surgery with comprehensive staging is recommended as initial surgery for patients who do not desire fertility preservation. Fertility-sparing surgery should be considered for those desiring fertility preservation regardless of stage. It should be monitored with ultrasound examinations, if necessary. Completion surgery should be considered after finishing childbearing.   

Surgery for Sex Cord-Stromal Ovarian Carcinoma   

Patients with stage IA or IC sex cord-stromal tumors desiring to preserve their fertility should be treated with fertility-sparing surgery with complete staging. It should be monitored with ultrasound examinations, if necessary. Completion surgery should be considered after finishing childbearing.  

Complete staging is also recommended for all other patients, but lymphadenectomy may be omitted for tumors grossly confined to the ovary. For metastatic or recurrent granulosa cell tumors, interval debulking surgery is recommended if feasible. 

Radiation Therapy

Examples: External beam radiation therapy (EBRT), brachytherapy  

Radiation therapy has a limited role in the treatment of ovarian carcinoma. It may be used as adjunctive therapy for stage II-IV malignant sex cord-stromal tumors with limited disease. It may be useful in the palliative phase to reduce complaints due to primary tumors or metastases. It is used for patients with symptomatic metastases to the bones, supraclavicular or inguinal node, or brain. It is also helpful in patients with pelvic localizations (eg complaints of nerve plexus compression, bleeding, pain or stasis). Palliative localized radiation therapy is also an option for recurrence treatment.