A Randomized Trial of Pelvic Radiation Therapy vs. No Further Therapy in Selected Patients With Stage IB Carcinoma of the Cervix

Abstract & Commentary

Synopsis: Adjuvant pelvic radiotherapy following radical surgery reduces the number of recurrences in women with stage IB cervical cancer at the cost of 6% grade 3/4 adverse events vs. 2.1% in the observation group.

Source: Sedlis A, et al. Gynecol Oncol 1999;73: 177-183.

Sedlis and colleagues evaluated the benefits and risks of adjuvant pelvic radiotherapy aimed at reducing recurrence in women with stage IB cervical cancer treated by radical hysterectomy and pelvic lymphadenectomy. Two hundred seventy-seven eligible patients were entered with at least two of the following risk factors: more than 1/3 stromal invasion, capillary lymphatic space involvement, and large clinical tumor diameter. Of 277 patients, 137 were randomized to pelvic radiotherapy (RT) and 140 to no further treatment (NFT). Twenty-one patients (15%) in the RT group and 39 (28%) in the NFT group had a cancer recurrence, 18 of whom were vaginal/pelvic in the RT and 27 in the NFT group. In the RT group, of 18 (13%) who died, 15 died of cancer. In the NFT group, of the 30 (21%) who died, 25 died of cancer. A life table analysis indicated a statistically significant (47%) reduction in risk of recurrence (relative risk = 0.53; P = 0.008) among the RT group, with recurrence-free rates at two years of 88% vs. 79% for the RT and NFT groups, respectively. Severe or life-threatening urologic adverse effects occurred in four (3.1%) in the RT group and two (1.4%) in the NFT group; three (2.3%) and one (0.7%) hematologic; four (3.1%) and zero gastrointestinal; and one (0.8%) and zero neurologic, respectively. One patient’s death was attributable to grade 4 GI adverse effects. Sedlis et al concluded that adjuvant pelvic radiotherapy following radical surgery reduces the number of recurrences in women with stage IB cervical cancer at the cost of 6% grade 3/4 adverse events vs. 2.1% in the NFT group.

Comment by David M. Gershenson, MD

This study demonstrates that adjuvant pelvic radiotherapy is superior to observation for patients with stage IB cervical cancer who undergo radical hysterectomy and pelvic lymphadenectomy and are found to have unfavorable factors in the primary tumor: deep stromal invasion, capillary lymphatic space involvement, and large tumor diameter. Importantly, all patients in this study had negative pelvic lymph nodes. In an accompanying editorial, Dr. Anthony Russell raises a much broader question with regard to this group of patients and the selection of primary treatment. He notes that at least 74 patients entered on this study had primary cancers larger than 4 cm and asks, "Since GOG 92 confirms that adjuvant pelvic radiation favorably impacts relapse-free survival, is it still appropriate to treat 4 cm and larger cancers of the cervix with attempted radical surgery?" In other words, many patients end up having both radical surgery and pelvic radiotherapy, thereby increasing the risk of complications as noted in this study. Russell is eloquent in his argument but, by no means, the first to raise this issue. This controversy is all the more important in view of a presentation of a more recent GOG study at this year’s annual meeting of the Society of Gynecologic Oncologists, in which Dr. William Peters presented data indicating that a combination of chemotherapy and radiation is superior to radiation alone following radical surgery for early-stage cervical cancer with positive pelvic lymph nodes.1 Size of the primary cervical cancer can be determined pretreatment, and the degree of lymphatic invasion and depth of invasion could be determined to varying degrees from generous cervical biopsies or conization. In 1999, we have to ask if we are doing our best for women with early cervical cancer.

Reference

1. Peters WA, et al. Gynecol Oncol 1999;72:443.

Based on recent information, all are acceptable contemporary treatments for various stages of cervical cancer except:
a. Radical surgery
b. Radiotherapy alone
c. Chemotherapy followed by radiation
d. Concomitant chemotherapy and radiation
e. Radiation followed by extrafascial hysterectomy