Epithelial Ovarian Cancer/Fallopian Tube Cancer/Primary Peritoneal Cancer

Clinical presentation:
Suspicious/ palpable pelvic mass on abdominal/pelvic exam and/or ascites, abdominal
distension
And/or
Symptoms without source of malignancy( (i.e bloating, pelvic/abdominal pain, difficulty eating
or feeling full quickly, urinary symptoms [urgency or frequency]) 
Workup:

 Abdominal/pelvic exam
 Ultrasound and/or abdominal/pelvic CT/MRI as clinically indicated
 Chest CT or chest xray as clinically indicated
 CBC, chemistry profile with liver function test (LFT)
 CA-125 or other tumor markers as clinically indicated
 Evaluate nutritional status
 GI evaluation as clinically indicated
 Obtain family history
 Refer to gynecologic oncologist for clinically suspicious lesions
Clinical Stage and Primary Treatment
1A (fertility desired) Unilateral salpingo-oophorectomy (USO)+ comprehensive surgical
staging
1B (fertility desired) Bilateral salpingo-oophorectomy(BSO) + comprehensive surgical staging
1A-IV, surgical candidate, optimal cytoreduction likely (fertility not desired) Total abdominal
hysterectomy (TAH/BSO)+ comprehensive staging and debulking as needed
Poor surgical candidate or low likelihood of optimal cytoreduction
Patients with ovarian cancer, fallopian tube cancer, or primary peritoneal cancer should have
genetic risk evaluation and BRCA1/2 testing (if not previously done)
Diagnosis by previous surgery or tissue biopsy (cytopathology) see workup, findings and
primary treatment

Poor Surgical Candidate or Low Likelihood of Optimal Cytoreduction Neoadjuvant Therapy

Primary Treatment
Evaluation by gynecologic oncologist and histologic confirmation (biopsy preferred) and/or
laparoscopic evaluation to determine feasibility of resection
 confirmed poor surgical candidate or low likelihood of optimal cytoreduction  neoadjuvant
therapy (category 1) and genetic risk evaluation and BRCA1/2 testing (if not previously done)
Response interval debunking surgery (IDS) with completion (TAH/BSO)and comprehensive
surgeryadjuvant therapy see maintenance therapy
Stable disease IDS with completion TAH/BSO and comprehensive staging or continue current
therapy (for a total of at least 6 cycles) or see therapy for persistent disease or recurrence IDS
with completion TAH/BSO and comprehensive staging or see therapy for persistent disease or
recurrence adjuvant therapy see maintenance therapy
Progressive disease see therapy for persistent disease or recurrence

Diagnosis by Previous Surgery

 Obtain family history

 Genetic risk evaluation (if not previously done)
 Evaluation by gynecologic oncologist (if not previously done)
 Chest xray or chest CT as clinically indicated
 CBC, chemistry profile with LFTs
 Institutional pathology review
 Ultrasound and/or abdominal/pelvic CT/MRI as clinically indicated
 Ca-125 or other tumor markers as clinically indicated
 Consider tissue diagnosis of metastatic sites

Adequate previous surgery and staging See pathologic staging

Incomplete previous surgery and/or staging:
1. Uterus intact
2. Adnexa intact
3. Omentum not removed
4. Documentation of staging incomplete
5. Residual disease, potentially resectable
6. Occult invasive carcinoma found at time of risk reduction surgery
7. Incomplete lymph node dissection
Findings:
Suspected stage IA or IB/ grade 1 or low grade surgical staging
Suspected stage IA or IB/grade 2 (non serous)
observation considered surgical staging
suspect residual disease completion surgery/surgical staging
suspect no residual disease completion surgery/surgical staging or chemotherapy

Suspected stage IA/IB high grade serous or grade 3 clear cell or stage IC
suspect no residual disease completion surgery/surgical staging or chemotherapy
suspect residual disease  completion surgery/surgical staging

Stage II, III, IV

Suspect potentially resectable residual disease  tumor reductive surgery
Suspect unresectable residual disease chemotherapy (6 cycles), evaluate for IDS prior to 4th
cycle
Suspect no residual disease see pathologic staging

Pathologic Staging
Stage IA or IB
Grade 2 endometrioid or Grade 3 endometrioid/high grade serous carcinoma observe/IV
platinum based therapy x 3-6 cycles [see primary regimens for stage I disease] consider
symptom management and best supportive care. Refer for palliative assessment, if appropriate,
see NCCN guidelines for palliative care and survivorship
Stage IC (grade 1, 2 or 3) IV platinum based therapy [see primary regimens for stage I
disease] consider symptom management and best supportive care. Refer for palliative
assessment, if appropriate. see NCCN guidelines for palliative care and survivorship see
monitoring/follow up
Stage II,III,IV platinum based chemotherapy [see primary regimens for stage II-IV disease],
completion surgery as indicated by tumor response and potential resectability in selected
patients consider symptom management and best supportive care. Refer for palliative
assessment if appropriate.
See NCCN guidelines for palliative care and survivorship see monitoring/follow up See
maintenance therapy
Stage II, III, IV Post Primary Treatment
Stage II,III,IV post primary treatment imaging as clinically indicated: chest/abdominal/pelvic
CT, MRI, PET/CT, or PET (skull base to mid thigh)
No bevacizumab used during primary therapy:
Complete clinical remission clinical trial or observe or Olaparib for BRCA1/2 mutations
(category 1 for germline mutations; category 2A for somatic mutations) see
monitoring/follow up
Partial remission Olaparib for BRCA1/2 mutations (category 1 for germline mutations;
category 2A for somatic mutations) or See therapy for persistent disease or recurrence see
monitoring/follow up
Progression see therapy for persistent disease or recurrence
Bevacizumab used as part of primary therapy:
Progression see therapy for persistent disease or recurrence
Partial or complete resection postremission bevacizumab or Olaparib for BRCA1/2 mutations
(category 1 for germline mutations; category 2A for somatic mutations) see
monitoring/follow up
Stable disease postremission bevacizumab see monitoring/follow up
Monitoring and Follow up
Stage I,II,III and IV after primary treatment

 Visits every 2-4 months for 2 years then 3-6 months for 3 years, then annually after 5
years
 Physical exam including pelvic exam
 Chest/abdominal/pelvic CT, MRI, PET/CT or PET(skull base to midthigh) as clinically
indicated
 Chest xray as indicated
 CBC and chemistry profile as indicated
 CA-125 or other tumor markers if initially elevated
 Refer for genetic risk evaluation if not previously done
 Long term wellness care
Rising CA-125, no previous chemotherapy or clinical relapse, no previous chemotherapy 

 Imaging studies as clinically indicated. Chest/abdominal/pelvic CT, MRI, PET/CT , or PET

 Tumor molecular testing if not previously done
Clinical Relapse, previous chemotherapy
  Imaging studies as clinically indicated. Chest/abdominal/pelvic CT, MRI, PET/CT , or PET
 Tumor molecular testing if not previously done
Serially rising CA-125, previous chemotherapy

 Imaging studies as clinically indicated. Chest/abdominal/pelvic CT, MRI, PET/CT , or

PET
 Tumor molecular testing if not previously done

Delay treatment until clinical relapse or immediate treatment for recurrent disease (category
2B) or clinical trial
Therapy for Persistent Disease or Recurrence
Progression on primary, maintenance or recurrence therapy or stable or persistent disease (if
not on maintenance therapy) or complete remission and relapse<6 months after completing
chemotherapy clinical trial and/or best supportive care and/or recurrence therapy
Complete remission and relapse >6months after completing prior chemotherapy
Radiographic and/or clinical relapse consider secondary cytoreductive surgery clinical trial
and/or combination platinum based chemotherapy preferred for first recurrence (category 1) or
recurrence therapy and/or best supportive care
Biochemical relapse (rising CA-125 and no radiographic evidence of disease) clinical trial or
delay treatment until clinical relapse or immediate platinum based recurrent therapy (category
2B) and/or best supportive care
Clinical trial or maintenance therapy (if partial or complete response)
Useful in certain circumstances:
Continue bevacizumab if previously treated with chemotherapy+ bevacizumab; or
Consider niraparib or olaparib or rucaparib
Or observe
Surgery and histologic diagnosis
Diagnosis

 Carcinosarcoma (malignant mixed Mullerian tumor)

 Clear cell carcinoma of the ovary
 Mucinous carcinoma of the ovary
 Grade 1 endometrioid carcinoma
 Low grade serous carcinoma
 Ovarian borderline epithelial tumors (low malignant potential)
 Malignant sex cord stromal tumors
  Malignant germ cell tumors

Carcinomas (MMMTs) of the ovary complete surgical staging stage I-IV chemotherapy as
per epithelial ovarian cancer or cisplatin/ifosfamide or carboplatin/ifosfamide or
paclitaxel/ifosfamide see monitoring/follow up

Clear cell carcinoma of the ovary

Stage IA IV platinum based therapy [see primary regimen for stage I disease] or observe
monitoring and follow up
Stage IB-C IV platinum based therapy [see primary regimen for stage I disease] monitoring
and follow up
Stage II-IV chemotherapy as per epithelial ovarian cancer
Mucinous carcinoma of the ovary
If not previously done: GI evaluation, CEA consider surgical staging if not previously done
Stage IA-IB observe or fertility sparing surgery for select patients (if not previously done)
monitoring/follow up
Stage IC observe or IV platinum based therapy x 3-6 cycles [see primary regimens for stage I
disease] or 5-FU + leucovorin+ oxaliplatin or capecitabine+ oxaliplatin or fertility sparing surgery
for select patients (if not previously done)
Stage II-IV chemotherapy [see primary regimens for stage II-IV disease] or 5FU+ leucovorin+
oxaliplatin +/- bevacizumab (category 2B for bevacizumab) or capecitabine+ oxaliplatin+/-
bevacizumab (category 2B for bevacizumab)
Borderline

Grade 1 endometrioid carcinoma

Stage 1A-1B observe monitor/follow up
Stage IC Observe (category 2B) or IV platinum based therapy x 3-6 cycles [see primary
regimen for stage I disease] or hormone therapy (category 2B) (i.e aromatase inhibitors
[anastrazole, letrozole, exemestane], leuprolide acetate, tamoxifen) see monitoring/follow up
Stage II-IV chemotherapy (see primary regimens) observe or maintenance hormonal
therapy (category 2B) (i.e aromatase inhibitors [anastrazole, letrozole, exemestane], leuprolide
acetate, tamoxifen)  see monitoring/follow up
Or
Primary hormonal therapy (category 2B) (i.e aromatase inhibitors [anastrazole, letrozole,
exemestane], leuprolide acetate, tamoxifen)  see monitoring/follow up
Borderline

Low grade serous carcinoma

Stage IA-IB observe see monitoring/follow up
Stage IC observe (category 2B) or IV platinum based therapy x3-6 cycles [see primary regimen
for stage I disease] or hormone therapy (category 2B) (i.e aromatase inhibitors [anastrazole,
letrozole, exemestane], leuprolide acetate, tamoxifen) see monitoring/follow up
Stage II-IV chemotherapy (see primary regimens) or primary hormonal therapy (category 2B)
(i.e aromatase inhibitors [anastrazole, letrozole, exemestane], leuprolide acetate, tamoxifen) 
observe or maintenance hormonal therapy (category 2B) (i.e aromatase inhibitors [anastrazole,
letrozole, exemestane], leuprolide acetate, tamoxifen) see monitoring/follow up
Ovarian Borderline Epithelial Tumors (Low Malignant potential)
Treatment

 Prior complete surgical resection:

o No Invasive implants  Observe
o Invasive implants  Treat as Low grade serous carcinoma (as mentioned above)
 Prior incomplete surgical resection  Chest/Abd/Pelvic CT with contrast:
o Residual disease remaining after 1st procedure:
 Fertility desired
 No invasive implants/Unknown  Observe (category 2B) OR
Fertility-sparing surgery and resection of residual disease
 Implants known  Fertility-sparing resection/Observe (category
3)/Treat as low grade serous carcinoma (LGSC)
 Fertility not desired
 No Implants/Unknown  Observe (category 2B) OR Completion
surgery and resection.
 Implants +ve  Completion surgery and resection/Observe
(category 3)/Treat as LGSC
o No Residual disease  Observe
Follow-up:

 Visits every 3-6 mo up to 5 years, then annually

 Physical (pelvic) exam
 Tumor markers including CA-125, if initially elevated
 If childbearing completed, consider completion surgery (category 2B)
 Lab analysis
 Imaging as indicated
 U/S for pt. with fertility sparing surgery.
Clinical Relapse:
Surgical evaluation + debulking (if appropriate)

 Non-invasive  Observe
 Implants of borderline (LMP)/ Low-grade invasive carcinoma  Treat as LGSC
 Invasive carcinoma (high grade)  Treat as epithelial ovarian cancer

Malignant Sex Cord-Stromal Tumors:

Presentation and Diagnosis
Stage IA/IC, Fertility desired  Fertility preserving surgery with staging
All other  Complete Staging
Treatment

 Stage I, Low risk  Observe and Surveil

 Stage I, High/Intermediate risk  Observe (2B) or Platinum-based chemotherapy
(category 2B)
 Stage II-IV  Platinum-based chemotherapy (2B) or RT for limited disease (2B)  If
Relapse  Clinical trial/ Secondary cytoreductive surgery or recurrence therapy

Malignant Germ Cell Tumors:

Initial Surgery

 Fertility desired  Fertility sparing surgery and comprehensive staging

 Not desired  Complete staging surgery
Prior Surgery

 Completely staged
 Incompletely staged
o Dysgerminoma or Grade 1 immature teratoma
 Positive imaging and tumor marker  Fertility sparing surgery with

staging OR Completion staging (according to preference
 Negative imaging but positive tumor markers  Observation (2B)
 Negative imaging and tumor markers  Observation (2B)
o Embryonal, Yolk sac tumor, grade 2-3 immature teratoma, choriocarcinoma or
Mixed histology tumor
 Positive imaging and tumor markers  Fertility sparing surgery OR with
possible tumor reductive surgery or Chemotherapy
 Negative Imaging and positive/negative tumor markers  See below for
treatment
Treatment, Follow up and Relapse
Stage I dysgerminoma or Stage I grade 1 immature teratoma  Observe (see surveillance
below)
Any stage embryonal tumor or yolk sac tumor or Stage II-IV dysgerminoma or Stage I, Grade
2/3 or Stage II-IV immature teratoma or Choriocarcinoma  Perform Chemotherapy and
monitor with Imaging as indicated.
Imaging results:

 If Recurrence  Additional chemotherapy (2B) or high-dose Chemo (2B). Observe, if

incomplete response consider Systemic therapy
 Residual tumor on imaging; markers normal  Consider surgical resection or Observe
o Necrotic tissue  Observe
o Benign teratoma  Chest/Abd/Pelvic CT or MRI
o Residual malignancy  Additional platinum-based chemo x2 cycles
 Persistently elevated markers with definitive residual disease  TIP
(paclitaxcel/ifosfamide/cisplatin) or High-dose chemo

Surveillance:
1. Dysgerminoma: Physical exam + tumor markers and Imaging
a. Year 1  Every 2-3 months. Abdomen/Pelvic CT (every 3-4 months)
b. Year 2  Every 3-4 months. Abdomen/Pelvic CT (every 4 months)
c. Year 3  Every 6 months. Abdomen/Pelvic CT (annually)
d. Year 4-5  Every 6 months. Abdomen/Pelvic CT (annually)
e. After 5 years  Annually. Imaging as clinically indicated.
2. Non-Dysgerminoma: Physical exam + tumor markers and Imaging
a. Year 1  Every 2 months. PA and lateral CXR & Abdomen/pelvic CT (every 3-4
months)
b. Year 2  Every 2 months. PA and lateral CXR & Abdomen/Pelvic CT (every 4-6
months)
 c. Year 3  Every 4-6 months. Abdomen/Pelvic CT (every 6-12 months)
d. Year 4-5  Every 6 months. Abdomen/Pelvic CT (every 6-12 months)
e. After 5 years  Annually. Imaging as clinically indicated.
3. Malignant Sex Cord-Stromal tumors:
a. Physical exam: Clinically indicated based on stage (6-12 months if low risk, 4-6
months if high risk).
b. Serum tumor markers: Clinically indicated if applicable it’s done based on stage.
c. Imaging: Reserved for patients with symptoms and elevated markers or
concerning findings on exam.

Principles of Surgery for Epithelial ovarian/Fallopian Tube/Primary peritoneal Cancer and less
common Histopathologies
General:

 Recommended that a gynecologic oncologist perform the surgery

 Open laparotomy is preferable in patients whom surgical staging, debulking or
secondary cytoreduction is planned
 Minimally invasive procedures can be used for select patients for interval debulking
procedure, but if that fails shift to open procedure
 Laparoscopy can be used to evaluate whether optimal cytoreduction can be achieved in
newly diagnosed patients
 Prior to surgery counsel patients about port placement if intra-peritoneal chemo is being
considered
Newly diagnosed invasive epithelial ovarian cancer confined to ovary or pelvis:

 Perform maximum cytoreduction and evaluate occult disease in abdomen and

retroperitoneum.
 In abdomen, peritoneal lavage or aspirate ascites for cytological abnormalities
 Biopsy suspicious surfaces, if none, perform random peritoneal biopsy.
 BSO and Hysterectomy with care to keep any encapsulated mass intact
 For preserving fertility perform USO or BSO sparing uterus
 Omentectomy should be performed
 Para-aortic lymph node dissection bilaterally at least till the level of Inferior mesenteric
artery and preferably to the level of renal vessels
 Pelvic Lymph node dissection
Newly diagnosed invasive epithelial ovarian cancer involving the pelvis and upper abdomen:

 Optimal cytoreduction (Residual disease <1 cm), however maximal effort should be
made to remove all gross disease.
  Aspiration of ascites and omentectomy should be performed.
 Suspicious and/or enlarged nodes should be resected, Negative nodes resection is not
required.
 Bilateral Pelvic and Para-aortic lymph node dissection in patients with tumor outside
pelvis <2 cm.
 Patients with low volume residual disease are potential candidates for IP therapy after
cytoreduction, port should be placed with initial surgery.
Interval Debulking Surgery (IDS) after neoadjuvant chemotherapy:

 IDS, including TAH and BSO with staging, should be performed after ≤4 cycles of chemo
or stable disease.
 Hyperthermic IP chemotherapy (HIPEC) with cisplatin can be considered for stage II
disease
 Biopsy/excise peritoneal surfaces found suspicious. Omentectomy should be performed
 Suspicious or Enlarged lymph nodes should be resected. Lymph node having potential
for metastasis may be removed.
Risk reducing Salpingo-Oophorectomy (RRSO) Protocol

 Laparoscopically survey the abdomen and pelvis and biopsy any abnormal peritoneal
findings.
 Obtain pelvic washings for cytology
 Perform total BSO, removing 2 cm of proximal ovarian vasculature/IP ligament, the tube
up to cornua, the peritoneum surrounding the ovaries, tubes and especially the
underlying areas of adhesion between tube and/or ovary with the pelvic sidewall.
 Both Ovaries and tubes should be placed in endobag for retrieval and processed
according to SEE-FIM protocol.
 If occult malignancy or serous tubal intraepithelial carcinoma is identified, refer to
gynecologist oncologist
 Salpingectomy alone is not yet proven, since the patient is still at risk for ovarian cancer.
Special circumstances

 Fertility-sparing surgery, includes USO or BSO (preserving uterus), can be considered for
early stage disease and/or low risk tumors. Clinical staging must be still be performed
but it may be omitted in pediatric patients with early stage malignant germ cell tumors.
 Primary Mucinous tumors of the ovary are uncommon. Thus, GI tract must be assessed
for occult malignancy and an appendectomy should be performed at initial surgery.
 Ovarian borderline epithelial (LMP) tumors: lymphadenectomy on improving survival
and upstaging is still debatable. Omentectomy and peritoneal biopsies may upstage
patients in 30% and may affect prognosis.
 Secondary cytoreduction can be considered in patients with recurrent ovarian cancer,
have isolated/limited focus of disease amenable to complete resection without ascites.
Ancillary Palliative Surgical procedures:

 Paracentesis/indwelling peritoneal catheter

 Thoracentesis/pleurodesis/video-assisted thoracoscopy/ indwelling pleural catheter
 Ureteral stents/nephrostomy
 Gastrotomy tube/intestinal stents/surgical relief of intestinal obstruction

Principles of Pathology:

 Most ovarian cancers including LCOH are diagnosed with the help of biopsies and
surgical specimens. Fine needle Aspirate (FNA) should be avoided as risk of rupture and
seeding is present. However, FNA can be used in patients who are not candidates for
debulking surgery.
 Primary peritoneal and fallopian tube cancers are diagnosed post-op if there is no
involvement of ovary. But some can be diagnosed pre-op if patient has already had
Bilateral oophorectomy. They’re treated in the same manner as epithelial ovarian cancer.
 CAP protocol for pathologic assessment:
o Tumor size and site
o Ovarian/Fallopian tumors: Surface involvement, Specimen integrity
o Histologic type and grade
o Extension and/or Implants
o Cytology
o Lymph node evaluation
o Serous tubal intraepithelial carcinoma (STIC, endometriosis [particularly if in
continuity with endometroid or clear cell carcinoma]), endosalpingiosis
o Next-gen sequencing for BRCA1/2 somatic mutations
o IHC for DNA MMR proteins or MSI testing via PCR
o Evaluation of homologous recombination deficiency

Less Common Ovarian Histopathologies:

 A borderline tumor is a primary epithelial lesion with cytologic features suggesting

malignancy but without clear invasion. Other terms used have been LMP and atypical
proliferative tumors.
 Borderline tumors are typically Serous or mucinous.
 Borderline may grossly resemble an invasive cancer but with absence of frank invasion
and invasive implants (implants rarely may occur).
 Clear Cell carcinoma are high grade tumors that may arise with endometriosis. Most
express Napsin A and are negative for WT1 and estrogen receptors.
 Primary mucinous ovarian tumors (PMOT) are difficult to distinguish with Metastasis
from GI origin. So, immunostaining is used, PAX8 positive for PMOT and SATB2 for
colonic origin.
  Endometroid Carcinoma, may be associated with Endometriosis, are usually positive for
CK-7, PAX8, CA-125 and estrogen receptors
 Now MMMTs are now considered a variant of poorly differentiated epithelial ovarian
cancer.
Special Circumstances:

 Other cancers involving adnexa: Uterine, Cervical, GI, Lymphoma

 For risk-reducing surgery, Fallopian tubes should be sectioned and examined extensively
along with the Ovaries.