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Cervical Cancer Treatment (Professional) (cont.)

Stage IIA Cervical Cancer

Either radiation therapy or radical hysterectomy results in cure rates of 75% to 80%. The selection of either option depends on patient factors and local expertise. A randomized trial reported identical 5-year overall survival (OS) and disease-free survival rates when radiation therapy was compared to radical hysterectomy.[1] The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[2] For patients with bulky (>6 cm) endocervical squamous cell carcinomas or adenocarcinomas, treatment with high-dose radiation therapy will achieve local control and survival rates comparable to treatment with radiation therapy plus hysterectomy. Surgery after radiation therapy may be indicated for some patients with tumors confined to the cervix that respond incompletely to radiation therapy or in whom vaginal anatomy precludes optimal brachytherapy.[3]

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.[4] The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy.[5] Treatment of patients with unresected periaortic nodes with extended-field radiation therapy leads to long-term disease control in those patients with low volume (<2 cm) nodal disease below L3.[6] A single study (RTOG-7920) showed a survival advantage in patients who received radiation therapy to para-aortic nodes without histologic evidence of disease.[7] Toxic effects were greater with para-aortic radiation than with pelvic radiation alone but were mostly confined to patients with prior abdominopelvic surgery.[7] Patients who underwent extraperitoneal lymph node sampling had fewer bowel complications than those who had transperitoneal lymph node sampling.[6,8,9] Patients with close vaginal margins (<0.5 cm) after radical surgery may also benefit from pelvic radiation therapy.[10]

Five randomized phase III trials have shown an OS advantage for cisplatin-based therapy given concurrently with radiation therapy,[11,12,13,14,15,16,17] while one trial examining this regimen demonstrated no benefit.[18] 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 included 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.[11,12,13,14,15,16,17,18,19]

Standard treatment options:

  1. Intracavitary radiation therapy combined with external-beam pelvic radiation therapy plus chemotherapy with cisplatin or cisplatin/5-FU for patients with bulky tumors.[11,12,13,14,15,16,20] 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 to LDR brachytherapy in terms of local-regional control and complication rates.[21,22,23][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as components of cervical cancer treatment.[24,25] Radiation therapy to para-aortic nodes may be indicated in primary tumors 4 cm or larger.
  2. Radical hysterectomy and pelvic lymphadenectomy. Radical surgery has been performed for small lesions, but the high incidence of compromised margins, parametrial spread, and positive nodes leading to postoperative radiation with or without chemotherapy make primary concomitant chemotherapy and radiation a more common approach.
  3. Postoperative total pelvic radiation therapy plus chemotherapy following radical hysterectomy and bilateral pelvic lymphadenectomy. Radiation therapy in the range of 50 Gy administered for 5 weeks plus chemotherapy with cisplatin with or without fluorouracil (5-FU) should be considered in patients with positive pelvic nodes, positive surgical margins, and residual parametrial disease.[11,12,13,14,15,16]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIA 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.

References:

  1. Landoni F, Maneo A, Colombo A, et al.: Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 350 (9077): 535-40, 1997.
  2. 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.
  3. Thoms WW Jr, Eifel PJ, Smith TL, et al.: Bulky endocervical carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys 23 (3): 491-9, 1992.
  4. Cunningham MJ, Dunton CJ, Corn B, et al.: Extended-field radiation therapy in early-stage cervical carcinoma: survival and complications. Gynecol Oncol 43 (1): 51-4, 1991.
  5. Downey GO, Potish RA, Adcock LL, et al.: Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection. Am J Obstet Gynecol 160 (5 Pt 1): 1055-61, 1989.
  6. Vigliotti AP, Wen BC, Hussey DH, et al.: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23 (3): 501-9, 1992.
  7. Rotman M, Pajak TF, Choi K, et al.: Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 274 (5): 387-93, 1995.
  8. Weiser EB, Bundy BN, Hoskins WJ, et al.: Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 33 (3): 283-9, 1989.
  9. Fine BA, Hempling RE, Piver MS, et al.: Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery. Int J Radiat Oncol Biol Phys 31 (4): 717-23, 1995.
  10. Estape RE, Angioli R, Madrigal M, et al.: Close vaginal margins as a prognostic factor after radical hysterectomy. Gynecol Oncol 68 (3): 229-32, 1998.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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.
  16. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.
  17. 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.
  18. 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.
  19. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.
  20. 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.
  21. 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.
  22. 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.
  23. 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.
  24. 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.
  25. 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.
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