By David M. Gershenson, MD
In the June 2001 issue of OB/GYN Clinical Alert, I discussed the reasons why American women were not receiving state-of-the-art care for endometrial cancer, excerpted from my Presidential Address to the American Radium Society.1 In that address, I also discussed the current status of cervical cancer and ovarian cancer treatment in the United States, and this article excerpts the former topic.
Cervical cancer is the third most common gynecologic malignancy in the United States, accounting for approximately 13,000 new cases in 2002.2 In this country, the major issue responsible for disparate practice patterns is one of specialty territoriality.
For patients with stage IA cervical cancer, surgery, with rare exceptions, is generally the treatment of choice. For patients with stage IB1, both radical hysterectomy and pelvic radiotherapy are acceptable choices, with individual treatment decisions based on multiple factors. For patients with stages IIA-IVA, based on information from 5 randomized trials, chemoradiation is the standard.3-7 Currently, the major area of controversy relates to stage IB2 cervical cancer-tumor confined to the cervix but 4 cm or greater in diameter. In my opinion, because of turf battles and physician bias, there is amazingly sparse useful information concerning the treatment of this subgroup. Granted, this entity is relatively uncommon, but the disagreement about the optimal treatment highlights some of the issues at work in other, more common cancers, such as prostate cancer.
Over the past 3 decades, oncologists have had the opportunity to definitively determine the optimal treatment for stage IB2 cervical cancer, but that opportunity may have been missed. Studies from the early 1970s indicated that survival and/or recurrence rates associated with radical hysterectomy and pelvic radiotherapy are equivalent in patients with stages IB and IIA cervical cancer, but these studies were plagued by selection bias and design flaws. In the 1970s and early 1980s, reports from M.D. Anderson Cancer Center described a reduced central failure rate in patients with so-called barrel-shaped cervical cancer (which were really large stage IB2) treated with combined-modality treatment-pelvic irradiation followed by extrafascial hysterectomy.8-10 The attention paid to combined-modality therapy significantly diverted the attention from the direct comparison of radical hysterectomy and pelvic radiotherapy for almost 2 decades. In addition, even though we ceased using this approach routinely at M.D. Anderson for bulky stage IB cervical cancer by about 1980, this attention spawned a randomized Gynecologic Oncology Group (GOG) trial in 1984 in which 282 patients with stage IB disease measuring 4 cm or greater were treated with either irradiation alone or irradiation followed by extrafascial hysterectomy.11 While the recurrence rate was reduced in the combined-modality group, the survival rates were not statistically different. Unfortunately, the final report of this trial has not yet been published.
In addition, for at least the past 2 decades, with the lack of convincing data, several gynecologic oncologists have promoted the practice of radical hysterectomy for stage IB2 cervical cancer. The rationale provided for such an approach includes the following: 1) preservation of ovarian function; 2) better post-treatment sexual function; 3) unavailability of expert radiation oncology; and 4) long-term complications of irradiation. Unfortunately, approximately three quarters of patients treated with radical surgery for stage IB2 receive postoperative irradiation or chemoradiation for factors such as positive lymph nodes, positive surgical margins, parametrial involvement, or deep stromal penetration.12 Patients who receive sequential modalities of radical surgery and irradiation obviously lose the benefits of surgery alone and incur a higher rate of significant complications. On the other hand, patterns of care studies have documented multiple problems with delivery of radiotherapy for cervical cancer, including suboptimal doses, protracted treatment times, and treatment of small numbers of patients in nonacademic facilities.13,14
In an Italian study, 343 patients with stage IB and IIA cervical cancer were randomly assigned to either radical hysterectomy or radiotherapy.15 Postoperative radiotherapy was administered to the subset of surgically treated patients with high-risk factors. Eighty-four percent of surgically treated patients with cervical cancers greater than 4 cm in diameter required adjuvant radiotherapy. Although there was no difference in overall survival between the 2 groups, patients who received both modalities of treatment had the worst morbidity. The GOG has recently conducted a randomized trial for patients with bulky stage IB cervical cancer comparing radical hysterectomy alone with neoadjuvant chemotherapy followed by radical surgery. After accrual of 231 patients in this trial, about one third had abandoned hysterectomy because of metastatic disease, another 18% or so required adjuvant radiotherapy, and another one third of patients would have been candidates for adjuvant radiotherapy in a previous GOG study.
In my opinion, the past 2 decades have been filled with missed opportunities and petty turf battles and self-serving practice patterns rather than a central focus on developing clinical trials that lead to better outcomes for patients. We are no closer to the truth than we were 20 years ago. As a gynecologic oncologist, I firmly believe that stage IB2 cervical cancer is best treated with chemoradiation, but there are no data to support my view. The fact that at least 75% of patients with stage IB2 cervical cancer treated with radical hysterectomy appear to receive adjuvant radiotherapy or chemoradiation for high-risk factors translates into increased cost and morbidity. Such an approach can only be justified by demonstrating superior survival rates.
Multiple factors account for the current status: 1) the unregulated nature of the American health care system; 2) conflicts of interest between physicians of different disciplines, and 3) lack of optimal clinical trials by academic institutions and cooperative groups. To improve the care of American women with cervical cancer, the existing paradigm requires dramatic change. Academic physicians and cooperative groups need to put aside their own self-interests and turf issues and design clinical trials that will lead to advances in patient outcomes most expeditiously. The multidisciplinary care model should be the standard. Radiation oncologists and gynecologic oncologists should be working together to arrive at the best treatment plan for each patient rather than competing with each other. The further development and refinement of evidenced-based practice guidelines is essential. And finally, with an uncommon yet important disease such as cervical cancer, I recommend consideration for establishment of centers of excellence across the country. Treatment would be multidisciplinary and state-of-the-art, and clinical trials could be optimized. And each center could have its own network of physicians and hospitals. Until some or all of these changes are affected, many American women will continue to receive suboptimal treatment for cervical cancer.
1. Gershenson DM. Cancer J. 2001;7:450-457.
2. Jemal A, et al. CA Cancer J Clin. 2002;52:23-47.
3. Morris M, et al. N Engl J Med. 1999;340:1137-1143.
4. Rose PG, et al. N Engl J Med. 1999;340:1144-1153.
5. Keys HM, et al. N Engl J Med. 1999;340:1154-1161.
6. Whitney CW, et al. J Clin Oncol. 1999;17:1339-1348.
7. Peters WA, et al. Gynecol Oncol. 1999;72:443-527.
8. Fletcher GH. Wm J Roentgenol Radium Ther Nucl Med. 1971;111:225-242.
9. Jampolis S, et al. Radiology. 1975;115:681-685.
10. O-Quinn AG, et al. Gynecol Oncol. 1980;9:68-79.
11. Keys HM, et al. Cancer J. 1997;3:117.
12. Finan MA, et al. Gynecol Oncol. 1996;62:139-147.
13. Montana GS, et al. Int J Radiat Oncol Biol Phys. 1995; 32:1481-1486.
14. Eifel PJ, et al. Int J Radiat Oncol Biol Phys. 1999;43: 351-358.
15. Landoni F, et al. Lancet. 1997;350:535-540.