Stage IVA Cervical Cancer

Current Clinical Trials

The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[1] After surgical staging, patients found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy.

Five randomized, phase III trials have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy,[2-8] while one trial examining this regimen demonstrated no benefit.[9] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which include the following:

• Metastatic disease in pelvic lymph nodes.
• Parametrial disease.
• Positive surgical margins.

Although the positive trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent, cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[2-10]

Standard treatment options:

• Radiation therapy plus chemotherapy: Intracavitary radiation therapy and external-beam pelvic radiation therapy combined with cisplatin or cisplatin/fluorouracil.[2-7,11]

Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication rates.[12-14][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as a component of cervical cancer treatment.[11,15,16]

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVA cervical cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

1. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.  [PUBMED Abstract]
   
   
2. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.  [PUBMED Abstract]
   
   
3. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.  [PUBMED Abstract]
   
   
4. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.  [PUBMED Abstract]
   
   
5. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.  [PUBMED Abstract]
   
   
6. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.  [PUBMED Abstract]
   
   
7. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.  [PUBMED Abstract]
   
   
8. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.  [PUBMED Abstract]
   
   
9. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.  [PUBMED Abstract]
   
   
10. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.  [PUBMED Abstract]
    
    
11. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.  [PUBMED Abstract]
    
    
12. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.  [PUBMED Abstract]
    
    
13. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.  [PUBMED Abstract]
    
    
14. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.  [PUBMED Abstract]
    
    
15. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.  [PUBMED Abstract]
    
    
16. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.  [PUBMED Abstract]