Updated 28 September 2007

Surgery for Presumed Ovarian Cancer in the Reproductive Age Group

As with any area of medicine, clinical judgment plays a large role in surgical decision making. Nowhere is this more important than in the approach to the pelvic mass. In the past surgical options were limited to laparotomy or observation (clinically or assisted by imaging). Now with the explosion of laparoscopic surgical techniques there is an increasing tendency to disregard the surgical principles previously used for diagnosing and treating pelvic masses.

Good clinical judgment should continue to be the basis of contemporary gynecologic practice and this good judgment is founded on proper history taking and examination of the patient. Those findings which raise the possibility of intrapelvic or intra-abdominal malignancy should dissuade the surgeon from an endoscopic approach. If a laparoscopic approach is contemplated for a pelvic mass the operator should have the appropriate skill level to remove the mass intact. Clinical guidelines should be used to help one determine which pelvic or adnexal mass is likely to be malignant.

The following table outlines some of the important factors in clinical decision making:

Factors Influencing Surgical Approach

Clinical:
Age of patient
Bilaterality
Fixed or solid
Ascites

Imaging:
Excrescences
Complex masses
Metastases
Ascites

Other:
Tumour markers: CA-125, CEA, AFP,  HCG

In young patients in the reproductive age group extensive pelvic endometriosis can mimic the findings of pelvic malignancy and present a diagnostic challenge.

It is a principle of oncology to try and remove tumour masses intact without rupture or spill to avoid the potential for spread of malignant cells. Though the medical literature is confusing on the effect of rupture on prognosis, there are many cases where tumour cells have demonstrated the ability to track along puncture sites and suture lines. This and most other cancer treatment centres would advocate no additional treatment for patients with an un-ruptured stage I grade 1 tumour. If leakage occurred, and especially where there is a delay in the definitive surgery, the patient would receive chemotherapy.

If the tumor can be removed intact with the use of endobags, etc. by a skilled laparoscopic surgeon then this may be appropriate. Aspiration of pelvic masses is not recommended for diagnosis. The aspiration of intracystic fluid seldom gives the diagnosis and may compromise prognosis. If the reason for the removal of a mass is suspicious of cancer then the mass should not be removed laparoscopically. Results reported by skilled laparoscopic surgeons in the world literature will not reflect the learning curve in clinical practice.

In early ovarian cancer once the diagnosis of malignancy has been made, a thorough staging laparotomy should be performed. This is particularly true if conservative surgery is contemplated to preserve fertility. Multiple peritoneal biopsies, pelvic and para-aortic node assessment and sampling, diaphragmatic biopsy and omentectomy are all important in ensuring that there is no subclinical extra-ovarian spread of disease. Wedge biopsy of the contralateral ovary is not required if the ovary is clinically normal as this may further compromise fertility.

Advanced Disease

The objective of surgery should be to reduce the residual disease to the lowest possible level. The literature has consistently shown that women who undergo optimal debulking surgery have a more favorable prognosis. Ideally the patient should be reduced to no visible residual disease after primary surgery. Survival advantage can also be seen for patients reduced to less than 2-centimeter size of largest residual nodule. Bowel resection and aggressive approach to peritoneal disease may be required to achieve this objective. These patients are often difficult to manage post-operatively due to large fluid shifts that can occur following extensive debulking surgery.

Interval Debulking

Secondary debulking surgery following chemotherapy has been advocated in recent years for women who have not had optimal debulking surgery at the time of their initial presentation. While this has been shown to improve the outlook for some of these patients it does not achieve the effectiveness of a good initial debulking procedure. For patients with a poor performance status, ECOG 2 or greater, or with stage IV disease, primary chemotherapy with reassessment for surgery after two or three cycles of treatment may be considered. 

Consideration should be given to referral of these patients to a gynecologic oncologist as the average practicing gynecologist will see at most one or two patients per year with the clinical profile of massive ascites and large fixed pelvic masses.

Developmental Studies

Due to the generally poor outcome of patients that present with extreme risk disease, multiple treatment options are being studied to improve these patients prognosis and disease free survival. The aim in this group of patients is to find treatment modalities that will prolong the time to symptomatic recurrence of the disease and at the same time provide this with a therapy that offers as little side effects as possible. Please contact the Gynecology Tumor Group for an update of new protocols that are in preparation or are currently being conducted.

First-Line Treatment

The BC Cancer Agency philosophy of post-operative management is to "tailor" the treatment to the patient, pursuing a curative intent where appropriate (the patient with no visible residual tumour), and providing high-grade palliation in those where cure is rarely possible (the patient intolerant of intensive therapy or with macroscopic residual).

Low Risk Group

Patients with stage Ia grade I tumours who have been appropriately staged have a high rate of cure with surgery alone.

Moderate and High Risk Groups (BC Cancer Agency Protocol GOOVCATM)

A curative intent, but more toxic program is appropriate for younger patients (those less than 70 years of age) with well maintained functional states (able to be up and about independently). We would suggest that all patients without visible residual tumour be referred to an Agency Clinic no later than cycle 2 of chemotherapy to facilitate timing of radiotherapy planning.

This program is modified as necessary. For example:

Ambulatory-care delivered carboplatin (AUC 6-7/1 hour) plus paclitaxel (175 mg/m²/3 hours) every 28 days for 3 cycles, followed by abdominal pelvic radiotherapy.

Some older patients (usually those over age 70) and those with an impaired performance (ECOG 2 or greater) status receive Carboplatin q4wks x 6

Those with a contraindication to radiotherapy (marked adhesions, vasculitis, severe inflammatory bowel disease) receive 6 cycles of chemotherapy

Extreme Risk Group (BC Cancer Agency Protocol GOOVCATX)

For patients with incomplete primary surgery interval debulking may be recommended. Patients with macroscopic residual tumour receive six cycles of carboplatin/taxol chemotherapy, with the option of an additional three cycles of carboplatin in those with a continuing improvement on treatment. Reference to the BC Cancer Agency for an opinion on interval debulking should be considered after cycle 2 chemo.

For those unable to tolerate such a program, single agent carboplatin is used.

Detailed standard protocols for moderate/high and extreme risk patients that include sample order sheets, doses modification schedules, and suggestions to toxicity are available. Please call the Gynecologic Oncology office at 877-6098, local 2365. Specific protocol information also available by contacting a member of the gynecologic oncology tumour group.

Relapsed Ovarian Cancer

Patients relapsing after a disease-free interval of at least 12 months may be eligible for repeat surgery or chemotherapy. Please do confer with a member of the gyne tumour group.

If patients have shown a high-quality and long-lasting response to initial platinum-based treatment, then Carboplatin can be used with a good chance of secondary response. However, if patients have responded poorly (less than a complete clinical response) or briefly (with a six month or shorter interval between treatment and relapse) then platinum-based treatment is less likely to be effective.

Patients with progressive, platinum-refractory ovarian cancer, i.e. the cancer grows while on carboplatin, may benefit from taxol (GOOVTAX3) if this agent was not a component of primary treatment. Given the expense and toxicity profile of taxol, the potential therapeutic ratio must be carefully considered. It is to be emphasized that the response rate of such disease to taxol is in the range of 10-20%, and complete clinical remissions are very infrequent. Taxol is not indicated for those with asymptomatic and/or non-progressive disease following conventional therapy, or those with bowel obstructions or a marked impairment of performance status. Other drugs potentially effective in this situation are oral etoposide, gemcitabine, topotecan, and vinorelbine.

Taxol and etoposide are available on formulary. Other drugs require submission of an "un-designated indication form".

Epithelial Tumours of Low Malignant Potential (Borderline)

Surgery is the cornerstone of therapy as per invasive ovarian cancer. For those desiring to maintain fertility unilateral salpingo-oophorectomy is adequate providing other ovary is clinically normal in abdominal exploration. In the rather uncommon circumstance of patients with low malignant potential ovarian tumours (borderline lesions), we continue to recommend a review of the pathology and determination of tumour DNA ploidy from flow cytometric assessment at the Vancouver Centre. In this way we can identify the minority of such patients with biologically more aggressive tumours (those with stage II or greater lesions with DNA aneuploidy and/or invasive extra-ovarian implants) that could benefit from further therapy.

Estrogen Replacement Therapy: Site Specific Information

The relationship between estrogen and ovarian cancer is obscure. It is known that there are both estrogen and progesterone receptors present in many epithelial ovarian tumours. Unfortunately, the effects of exogenous hormones on these receptors are not well known. There is no evidence that estrogen has either the potential to promote recurrence or to decrease the time to recurrence.

In the absence of scientific evidence to the contrary, it is not felt necessary to withhold estrogen replacement therapy from any symptomatic woman with ovarian malignancy regardless of risk category.

Recommendation:

In absence of a uterus, estrogen alone.

With uterus in situ, continuous estrogen plus progesterone.

Chemotherapy Protocols - Gynecology

Intraperitoneal chemotherapy - pdf file