Commentary (Basil): Management of Early Ovarian Cancer

Dr. Sonoda has provided a thorough summary of the management of early-stage ovarian cancer. He highlights the importance of accurate and complete surgical staging of this disease entity. Laparoscopic staging is discussed as a potential alternative to the classic open laparotomy staging procedure. In addition, the author includes an extensive review of trials discussing chemotherapy, radiation therapy, and intraperitoneal therapy as adjuvant treatment for early-stage disease. Staging Issues
The majority of epithelial ovarian cancers are not detected until they have advanced to stage III/IV disease. The survival of patients with earlystage (I/II) disease is quite favorable when compared to patients diagnosed with advanced disease. This fact alone highlights the extreme importance of complete surgical staging. In a classic paper by Young and colleagues, 31% of patients thought to have early-stage ovarian cancer (stage IA-IIB) were found to have a higher stage when systematically restaged.[1] Of those who were upstaged, the majority (77%) were found to have stage III disease. These findings underscore the importance of complete surgical staging. One can see how treatment planning and prognosis may be affected as there is a general consensus that patients with stage IA/B, grade 1/2 disease require no postoperative therapy after complete surgical staging. Dr. Sonoda notes that complete surgical staging is most often accomplished when a gynecologic oncologist performs the procedure. In many situations, less than 50% of patients with early-stage ovarian cancer are initially treated by a gynecologic oncologist. Meyer et al reported a significant actuarial and disease-free survival advantage to early-stage (I/II) ovarian cancer patients who were operated on by a gynecologic oncologist (as opposed to a nononcologist).[ 2] It has also been demonstrated that gynecologic oncologists are more likely to optimally cytoreduce advanced- stage ovarian cancer (to < 1 cm).[3] Patients who have undergone optimal cytoreduction exhibit a clear survival advantage over those who are suboptimally reduced. Prompt referral to a gynecologic oncologist should be made given any of the clinical scenarios in the author's Table 3 (Society of Gynecologic Oncologists guidelines for referral to a gynecologic oncologist). Failure to inform patients of the potential advantages of being treated by a gynecologic oncologist is a disservice to them. Laparoscopy is becoming more commonplace in the field of gynecologic malignancies. Studies specifically focused on early-stage ovarian cancer universally include small numbers of patients. As more data are collected and surgical techniques improve, the use of laparoscopy in early- stage ovarian cancer will likely be better defined. Treatment Options
The cornerstone of therapy for early-stage ovarian cancer is surgery. Historically, several methods of postoperative adjuvant therapy have been employed for patients with early disease. These include chemotherapy, radiation therapy, and intraperitoneal delivery of chemotherapy or radioactive isotopes. Additionally, adjuvant therapy in low-risk earlystage ovarian cancer patients may provide no better outcome than surgery alone. Completely staged patients with stage IA/B, grade 1/2 tumors with a non-clear-cell histology have a good prognosis and require no adjuvant therapy. Adjuvant therapy is generally advocated for patients with stage IC/II or grade 3 tumors. These characteristics are considered poor prognostic factors. Many studies have been performed to evaluate adjuvant therapy in early-stage ovarian cancer. It is crucial to determine how each study defines surgical staging. Also critical to the evaluation of these data is the number of patients in these studies who underwent complete surgical staging. In general, the chemotherapy arms of many of these studies show a significant advantage in patients who were incompletely staged. The assumption is that a proportion of these incompletely staged patients actually have more advanced disease, and this may account for decreased risk of recurrence or improved overall survival. The type of chemotherapy and the number of cycles patients with earlystage ovarian cancer and poor prognostic factors should receive is a matter of debate. A recent Gynecologic Oncology Group (GOG) study was presented comparing six cycles of carboplatin (Paraplatin), at an area under the concentration-time curve (AUC) of 7, plus paclitaxel, 175 mg/m², to three cycles in this patient population.[ 4] No significant difference was detected in recurrence rates between these two arms; however, toxicity was significantly greater among patients receiving six cycles. At our institution, patients with early-stage ovarian cancer and poor prognostic factors are treated with a regimen of carboplatin and paclitaxel for three cycles. The carboplatin dose used varies between an AUC of 5 and 7.5. Intraperitoneal chemotherapy for early-stage ovarian cancer, much like that for advanced-stage optimally cytoreduced ovarian cancer, is unlikely to gain universal favor. The same potential benefits of this method of administration exist, such as direct exposure of tumor cells to the chemotherapeutic agent and increased drug concentration to the tumor. As Dr. Sonoda states, the advantages of intraperitoneal chemotherapy over intravenous chemotherapy have yet to be proven. In some studies, intraperitoneal radiotherapy has been shown to be similar to intravenous chemotherapy in this patient population, but because of toxicity and issues with ease of administration, this method is not in widespread use. Lastly, external-beam irradiation has been used for early-stage disease. Whole abdominal radiation compared to some chemotherapy regimens has produced similar recurrence and survival results. No existing data show that whole abdominal radiation is superior to carboplatin and paclitaxel in early-stage ovarian cancer patients. Summary
In summary, it is vital that patients with early ovarian cancer be completely staged. This is accomplished most often when a gynecologic oncologist is involved in the surgery. Patients with stage IA/B, grade 1/2 tumors can be treated with surgery alone. Patients with early-stage ovarian cancer and poor prognostic factors can be treated in a variety of ways, but carboplatin and paclitaxel for three cycles is an acceptable and generally well-tolerated regimen.

Disclosures:

The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Young RC, Decker DG, Wharton JT, et al: Staging laparotomy in early stage ovarian cancer. JAMA 250:3072-3076, 1983.
2. Mayer AR, Chambers SK, Graves E, et al: Ovarian cancer staging: Does it require a gynecologic oncologist? Gynecol Oncol 47:223-227, 1991.
3. Eisenkop SM, Spirtos NM, Montag TW, et al: The impact of subspecialty training on the management of advanced ovarian cancer. Gynecol Oncol 47:203-209, 1992.
4. Bell J, Brady M, Lage J, et al: A randomized phase III trial of three versus six cycles of carboplatin and paclitaxel as adjuvant treatment in early stage ovarian epithelial carcinoma: A GOG study (abstract 1). Presented at the 34th Annual Meeting of the Society of Gynecologic Oncologists, Jan 31– Feb 4, 2003, New Orleans.