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3. Diagnosis and Staging

Diagnosis requires thorough clinical, surgical and pathologic assessment.

3.1 Pre-Operative Assessments

  • Complete history and physical, including pelvic and pelvi-rectal examinations
  • CBC, BUN, Cr
  • Tumor markers: CA125 and CEA in all patients. CA19-9 and CA15-3 are associated with breast and gastrointestinal tract cancers; however they may also be elevated in clear cell carcinomas, endometrioid carcinomas and dermoid cysts (CA19-9). 
  • AFP, HCG (quantitative), LDH in patients under 40 (associated with germ cell tumours)
  • Chest X-ray
  • Some type of imaging is informative.  Pelvic ultrasound will help to determine level of suspicion (worrisome features include solid areas, increased vascular flow, bilaterality, ascites, excrescences, mural nodules etc.). CT chest/abdomen/pelvis with contrast is recommended for suspected stage III/IV disease or for suspected HGSC histology, to rule out peritoneal dissemination and for treatment planning and/or the need for referral to a gynecologic oncologist for consideration of surgery.

3.2 Surgery

It is highly recommended that patients presenting with apparent advanced staged ovarian cancer on imaging be referred for subspecialist care (Gynecologic Oncologists). Decisions regarding upfront surgery to achieve optimal debulking vs. pre-operative chemotherapy if optimal debulking is not possible or is not medically appropriate are made within a multidisciplinary team.

Surgery provides staging and prognostic information, and it may be therapeutic through removal of diverse clonal populations. Successful treatment of EOC often begins with surgical management, including surgical cancer staging for early apparent disease, and tumour debulking for advanced stage disease. Staging procedures have changed over the last decade with an appreciation of i) differences in disease distribution and clinical course according to the histotype, and ii) recognition that fertility sparing staging procedures can be appropriate in some situations. Core components of staging usually include removal of the fallopian tubes and ovaries (BSO), removal of the uterus (hysterectomy), omentectomy, directed biopsies, washings, +/- assessment of retroperitoneal lymph nodes (pelvic and/or para-aortic lymphadenectomy).  

The 3 most important prognostic factors influencing outcome of EOC are stage, tumour grade and the presence or absence of visible residual disease at the completion of initial surgery. In apparent early stage ovarian cancer, complete staging with multiple biopsies and possibly lymphadenectomy is key to ruling out microscopically advanced disease. Fertility sparing surgery in young women may be acceptable with specific histotypes (such as endometrioid carcinoma, LGSC, and borderline tumors) when the contralateral ovary and uterus are uninvolved.

When patients present with apparent advanced stage disease, decisions regarding upfront surgery to achieve optimal debulking vs. pre-operative chemotherapy if optimal debulking is not possible or is not medically appropriate are made with a multidisciplinary team. Well-conducted RCTs demonstrate that clinical outcomes for women treated by upfront surgery, or by pre-operative chemotherapy followed by surgery are the same16, 17. In fact, those receiving pre-operative chemotherapy experience slightly lower rates of surgical complications. In some cases, a diagnostic laparoscopy may be required to decide whether primary surgery or pre-operative chemotherapy is the best initial strategy, based on distribution and volume of disease.  

3.3 Biopsy for patients requiring delayed debulking

If the decision is made to start with pre-operative chemotherapy, a histologic diagnosis is required before treatment is initiated. For this, a core biopsy is preferred. Any elevated tumour marker should be monitored during therapy (e.g. CA-125, CA15-3, CA 19-9) and re-evaluation for surgery is recommended after the patient has had 2-3 cycles of chemotherapy delivered. A CT scan is important prior to a consultation with the Gynecologic Oncologist after these 2-3 cycles to determine response to chemotherapy as well as the likelihood of optimal debulking at the time of delayed primary surgery.

If a pre-treatment biopsy cannot be obtained, or is not technically successful, consideration can be given to upfront surgery or a laparoscopic biopsy. Although not ideal, cytologic evaluation of fluids (ascites or peritoneal effusions) can be used. In such cases, we consider measuring serum CA125:CEA ratio as some studies shows this ratio >25 to support the diagnosis of a primary ovarian/primary peritoneal/fallopian tube cancer18. Care should be taken to rule out other primary cancers. In addition, low-grade diseases such as low-grade serous carcinoma are unlikely to respond to chemotherapy and will more likely benefit from surgical debulking. For any patient in whom the response to chemotherapy is poor, pathology should be scrutinized/reconsidered. 

Delayed primary debulking surgery is best performed after 3 or 4 cycles of pre-operative chemotherapy. Post-delayed debulking, it is customary to deliver chemotherapy to complete at least 6 cycles in total, with no fewer than 2 post-operative cycles given (i.e., sometimes the total number of cycles will exceed 6).

3.4 Staging classification

Classification Criteria (FIGO) for Epithelial Ovarian, Fallopian Tube and Primary Peritoneal Cancers is as follows and accessible through FIGO, SGO, and other websites: 

Table 1: FIGO and TNM staging

Tumour limited to one ovary (capsule intact) or fallopian tube
No tumour on ovarian or fallopian tube surface
No malignant cells in the ascites or peritoneal washings
Tumour limited to both ovaries or fallopian tubes
No tumour on ovarian or fallopian tube surface
No malignant cells in the ascites or peritoneal washings
Tumour limited to one or both ovaries or fallopian tubes, with any of the followings:
IC1 – surgical spill intraoperatively
IC2 – capsule ruptured before surgery or tumour on ovarian or fallopian tube surface
IC3 – malignant cells present in the ascites or peritoneal washings
Tumour involves one or both ovaries or fallopian tubes with pelvic extension (below pelvic brim) or peritoneal cancer (Tp)
Extension and/or implants on the uterus and/or fallopian tubes and/or ovaries
Extension to other pelvic intraperitoneal tissues
Tumour involves one or both ovaries or fallopian tubes, or primary peritoneal cancer, with cytologically or histologically confirmed spread to the peritoneum outside of the pelvis and/or metastasis to the retroperitoneal lymph nodes
Metastasis to the retroperitoneal lymph nodes with or without microscopic peritoneal involvement beyond the pelvis
IIIA1 - Positive retroperitoneal lymph nodes only (cytologically or histologically proven)
IIIA1(i) metastasis <= 10mm in greatest dimension 
IIIA1(ii) metastasis > 10mm in greatest dimension

IIIA2 - Microscopic extrapelvic (above the pelvic brim) peritoneal involvement with or without positive retroperitoneal lymph nodes
oneal lymph nodes
T3a N0/1
Macroscopic, extrapelvic, peritoneal metastasis ≤ 2 cm ± positive retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen.
T3b N0/1
Macroscopic, extrapelvic, peritoneal metastasis > 2 cm ± positive retroperitoneal lymph nodes. Includes extension to capsule of liver/spleen.
T3c N0/1
Distant metastasis excluding peritoneal metastasis
Pleural effusion with positive cytology
Metastasis to extra-abdominal organs (including inguinal lymph nodes and lymph nodes outside of abdominal cavity) or parenchymal metastasis

Other considerations are as follows:

  • Histologic type including grading should be designated at staging;
  • Primary site (ovary, fallopian tube or peritoneum) should be designated where possible;
  • Tumors that may otherwise qualify for stage I but involved with dense adhesions justify upgrading to stage II if tumor cells are histologically proven to be present in the adhesions.
Of note, staging for primary fallopian tube and primary peritoneal carcinomas of high-grade serous type is similar. Indeed modern pathology criteria now consider ovarian serous, primary peritoneal, fallopian tube serous carcinomas as encompassed by pelvic (non-uterine) serous carcinoma. Table 1 summarizes the criteria for assignment of primary tumor site.

Table 2: Criteria for designation of primary tumor site in high-grade serous carcinoma

Fallopian tube
Primary Peritoneal Carcinoma
  • STIC present
  • Tumor involving fallopian tube mucosa
  • Fallopian tube encased in tubo-ovarian mass
  • Ovarian tumor without STIC or fallopian tube mucosal involvement
  • Both ovaries and fallopian tubes normal and examined in entirety

SOURCE: 3. Diagnosis and Staging ( )
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