Cervical cancer: Combined modality therapy

Prospective, randomized studies conducted over the past 10 years have chang ed the management of patients with advanced cervical cancer. The reviewed s tudies evaluated the use of surgery, irradiation, and chemotherapy in patie nts with various stages of cervical carcinoma in the absence and presence o f high-risk factors for recurrence. A study by the Radiation Therapy Oncolo gy Group (RTOG) compared pelvic with pelvic plus prophylactic para-aortic i rradiation in patients with stages IB (> 4 cm), IIA, and IIB cervical cance r. The 10-year survival advantage was 11% for patients treated with prophyl actic para-aortic irradiation. A follow-up study compared pelvic plus proph ylactic para-aortic irradiation and brachytherapy with pelvic irradiation, brachytherapy, and chemotherapy with cisplatin and 5-FU in patients with IB -to IVA-stage cervical cancer. Overall and disease-free survivals were sign ificantly improved in patients receiving chemotherapy. In patients with a p revalence of stage IIB and III, the Gynecologic Oncology Group (GOG) demons trated that treatment with hydroxyurea alone was inferior to cisplatin or c isplatin, 5-FU, and hydroxyurea in patients treated concurrently with pelvi c irradiation and brachytherapy, and the GOG adopted irradiation and weekly cisplatin as standard therapy. Further GOG studies suggest that irradiatio n and weekly cisplatin chemotherapy without hysterectomy is the optimal tre atment for patients with stage IB cervical cancer. High-risk factors for re currence include tumor size, depth of tumor invasion, lymphovascular space involvement, and lymph node involvement. Prospective, randomized studies co nducted by the GOG evaluated the effectiveness of various treatments in pat ients with high-risk factors. In one study that did not use chemotherapy, t he recurrence-free interval was about 10% better for stage IB patients rece iving postoperative irradiation after radical hysterectomy and pelvic lymph adenectomy compared with those who received no further therapy. Patients wi th Stages IB and IIA disease who, following radical hysterectomy and lymph node dissection, are identified as having positive pelvic lymph nodes and p ositive parametrial involvement, are at higher risk for recurrence and deat h than the high-risk group described above. An intergroup study conducted b y the GOG, RTOG, and Southwest Oncology Group compared postoperative pelvic irradiation alone with postoperative pelvic irradiation plus concurrent ch emotherapy in this group of patients. Overall and progression-free survival s were superior for patients receiving chemotherapy, and their greatest sur vival occurred in patients who received 3 or 4 chemotherapy cycles compared with 1 or 2 cycles or no chemotherapy. These findings are summarized with respect to their implications for treatment of patients with advanced cervi cal cancer.