Drs. Randall and Rubin address three subjects important to all patients with advanced-stage epithelial ovarian cancer: (1) the incidence and annual mortality associated with the disease, (2) the use of intestinal surgery at the time of initial surgery, and (3) the use of surgery for intestinal obstruction in patients with recurrent (or progressive) ovarian cancer. I believe that progress in all three areas has been made, albeit slowly.
Incidence and Annual Mortality
The authors begin with an often cited statistic: “Ovarian cancer afflicts more than 26,600 women in the United States each year, and over 14,500 die of the disease.” They are absolutely correct that “it is thus the deadliest gynecologic malignancy, associated with more fatalities than all the other gynecologic cancers combined.” We are, however, experiencing a dramatic decrease in the annual incidence and mortality of this disease.
In 1971, then president Richard M. Nixon declared the “war on cancer.” Regrettably, in the quarter of a century since that proclamation (1971 to 1996), the number of deaths from ovarian cancer in the United States increased by 48%, from 10,000 in 1971 to 14,800 in 1996 (Table 1). Many past case control studies reported that women who took oral contraceptives had significantly lower rates of ovarian cancer, but there were no data until now supporting the fact that oral contraceptives, discovered by John Rock and Gregory Pincus and approved for use by the Food and Drug Administration in 1960, actually influenced the incidence and mortality of this disease.
As can be seen in Table 1, the steady rise in the incidence and mortality of ovarian cancer for the quarter century after the “war on cancer” was declared is for the first time showing a dramatic decrease—from 26,700 cases in 1996 to the predicted incidence of 23,000 for the year 2000, and from 14,800 deaths in 1996 to a predicted mortality of 14,000 for the year 2000. Researchers attributed the decline in incidence to the effect of oral contraceptive use that began in the 1960s.
Intestinal Surgery for Advanced-Stage Disease
The authors posit that “. . . even patients with apparent extensive intestinal involvement at the time of presentation rarely benefit from aggressive bowel resection unless this effort is performed for complete obstruction or as part of an optimal surgical cytoreduction.”
In 1978, Griffiths and Fuller presented a compelling study of the benefits of cytoreductive surgery in advanced-stage ovarian cancer. They demonstrated that women with stage III or IV ovarian cancer and with postoperative tumor nodules less than 1.6 cm in diameter not requiring cytoreductive surgery had a 40-month survival of approximately 20%. This compared to a similar 30% survival at 40 months for patients who underwent cytoreductive surgery that resulted in tumor nodules less than 1.6 cm in diameter. In dramatic contrast, no patient with residual tumor nodules greater than 1.6 cm survived 40 months.
Based on this seminal work of Griffiths and Fuller, we initiated a prospective trial in 1980 in 50 patients with stage III or IV ovarian cancer to evaluate what percentage of these women could have tumors optimally cytoreduced (then defined as £ 2 cm) and what type of surgery was needed to achieve optimal cytoreduction. Optimal cytoreduction (£ 2 cm) was achieved in 38 (76%) of the 50 patients. This required intestinal surgery at the time of initial operation in more than one-third of these patients (Table 2).
Intestinal surgery most commonly involved resection and reanastomosis of the rectosigmoid colon because of obstruction or impending obstruction. Therefore, any oncologic surgeon, general surgeon, or gynecologic oncologist, who takes on the responsibility of operating on a patient with presumed advanced-stage ovarian cancer must be prepared to perform intestinal surgery if such surgery is required for optimal cytoreduction. This necessitates that such patients undergo preoperative bowel preparation in case intestinal surgery is required.
Surgery for Intestinal Obstruction in Recurrent Disease
Of all the subjects discussed by the authors, the management of intestinal obstruction in patients with recurrent ovarian cancer may be the most difficult for the oncologic surgeon. Dr. Rubin reported in 1989 on the experience of the Memorial Sloan-Kettering Cancer Center in patients with intestinal obstruction secondary to progressive ovarian cancer between the years 1983 and 1985. Since the authors present no new data from their current institution, I assume little has changed in the author’s approach to intestinal obstruction during the 11 years since that report.
In that review, the mean survival was 6.8 months for patients in whom surgery corrected the intestinal obstruction, compared to 1.8 months for those in whom only an exploratory laparotomy was performed. My experience between 1971 and 1980 was not significantly different from that reported by the authors. The median survival of 60 women with progressive ovarian cancer and intestinal obstruction at Roswell Park Cancer Center was only 2.5 months (< 1 to 27 months) and did not differ significantly with the type of surgery performed: small intestine bypass, 4 months; ileostomy, 2 months; small intestine resection, 1 month; colostomy, 2.5 months; and exploratory laparotomy, 2 months (Table 3). However, much has changed in the management of women with progressive ovarian cancer since these two early reports.
First, during those earlier years, most patients were treated with single, alkylating agents and the use of cisplatin (Platinol)-based chemotherapy was just beginning. The authors rightly point out that the decision to consider surgical correction of intestinal obstruction in recurrent ovarian cancer is based on whether the patient’s tumor was initially sensitive to platinum compounds.
In addition, oncologists now have many more options in addition to platinum compounds for second-line chemotherapy not available in the 1970s and 1980s, including paclitaxel (Taxol), topotecan (Hycamtin), gemcitabine (Gemzar), altretamine (Hexalen), liposomal doxorubicin (Doxil), oral etoposide (VePesid), and vinorelbine (Navelbine), if the intestinal obstruction can be surgically corrected (Table 4).
No one can disagree with the authors’ statement that “physicians must use careful judgement in selecting patients whose prognosis is sufficiently favorable so that they may enjoy some benefit in quality of life from surgical correction of intestinal obstruction.”
However, even for the experienced oncologic surgeon, there is no preoperative testing that will predict whether surgical correction of intestinal obstruction is possible. Therefore, if conservative management (as outlined by the authors) is not effective, given that there are now many new second-line agents available for progressive ovarian cancer, exploratory surgery for possible correction of an intestinal obstruction should at least be discussed with the patient and her family.
This latter conclusion is in total agreement with Dr. Rubin’s 1999 editorial on intestinal obstruction in ovarian cancer, in which he wrote, “As with most difficult medical decisions where management options are not clearly defined, the best course is usually to present the reasonable alternatives to the patient and her family as clearly as possible, and let the patient decide.”
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2. Gnagy S, Ming EE, Devesa SS, et al: Declining ovarian cancer rates in US women in relation to parity and oral contraceptive use. Epidemiology 11:102-105, 2000.
3. Griffith CT, Fuller AF: Intensive surgical and chemotherapeutic management of advanced ovarian cancer. Surg Clin North Am 58:31-142, 1978.
4. Piver MS, Baker T: The potential for optimal (£ 2 cm) cytoreductive surgery in advanced ovarian carcinoma at a tertiary medical center: A prospective study. Gynecol Oncol 24:1-8, 1986.
5. Rubin SC, Hoskins WJ, Benjamin I, et al: Palliative surgery for intestinal obstruction in advanced ovarian cancer. Gynecol Oncol 34:16-19, 1989.
6. Piver MS, Barlow JJ, Lele SB, et al: Survival after ovarian cancer induced intestinal obstruction. Gynecol Oncol 13:44-49, 1982.
7. Rubin SC: Intestinal obstruction in advanced ovarian cancer: What does the patient want? Gynecol Oncol 75:311-312, 1999.