J Korean Med Sci.  2006 Aug;21(4):683-689. 10.3346/jkms.2006.21.4.683.

Survival Benefits of Neoadjuvant Chemotherapy Followed by Radical Surgery versus Radiotherapy in Locally Advanced Chemoresistant Cervical Cancer

• Choi YS
• Sin JI
• Kim JH
• Ye GW
• Shin IH
• Lee TS

• KMID: 2157821
• DOI: http://doi.org/10.3346/jkms.2006.21.4.683

Abstract

The aim of this study was to analyze long-term survivals in patients with stage IB to IIA cervical cancer treated by neoadjuvant chemotherapy setting. Between February 1989 and January 1998, 94 women with previously untreated stage IB to IIA carcinoma of the uterine cervix who received cisplatin based neoadjuvant chemotherapy were enrolled in this study. All of patients with chemoresponse (complete response, n=15; partial response, n=47) and 16 patients with chemoresistance received radical surgery (RS group). The other 16 patients with chemoresistance received radiotherapy for definite treatment (RT group). In the RS group, the 10 yr survival estimation in patients with bulky tumors (diameter > or =4 cm, n=26) was similar to that with non-bulky tumors (83.3% vs. 89.3%, p=NS). In selected patients with chemoresistance, those treated by radiotherapy (n=16) showed significantly poorer survivals than those treated by radical surgery (n=16) [10 yr survival rates of RT (25%) vs. RS (76.4%), p=0.0111]. Our results support that a possible therapeutic benefit of neoadjuvant chemotherapy plus radical surgery is only in patients with bulky stage IB to IIA cervical cancer. In cases of chemoresistance, radical surgery might be a better definite treatment option.

Keyword

Neoadjuvant Therapy; Hysterectomy, Radiotherapy; Uterine Cervical Neoplasms

MeSH Terms

Uterine Cervical Neoplasms/drug therapy/*radiotherapy/*surgery
Treatment Outcome
Survival Analysis
Retrospective Studies
Prognosis
Neoplasm Staging
Multivariate Analysis
Middle Aged
Humans
Follow-Up Studies
Fluorouracil/administration & dosage
Female
Drug Resistance, Neoplasm
Combined Modality Therapy
Cisplatin/administration & dosage
Chemotherapy, Adjuvant
Antineoplastic Combined Chemotherapy Protocols/therapeutic use
Adult

Figure

• 

  Fig. 1 Treatment and patient allocation in this study. NACT, neoadjuvant chemotherapy; CR, complete response; PR, partial response; RS, radical surgery group treated by neoadjuvant chemotherapy plus radical surgery; RT, radiotherapy group treated by neoadjuvant chemotherapy plus radiotherapy; BPND, bilateral pelvic node dissection.

• 

  Fig. 2 Survival estimation by Kaplan Meier's method of whole series. Five and 10 yr survival rates were 80.7% and 77.0%, respectively.

• 

  Fig. 3 Survival estimation by Kaplan Meier's method according to definite therapy following neoadjuvant chemotherapy in patients who showed stable disease after neoadjuvant chemotherapy. Five year survival estimation of stable disease in RS and RT group was 76.4% vs. 37.5%, and 10 yr survival estimation was 76.4% vs. 25%. This difference was statistically significant (p=0.0111) by Log rank test. NACT, neoadjuvant chemotherapy; RS, radical surgery group treated by neoadjuvant chemotherapy plus radical surgery; RT, radiotherapy group treated by neoadjuvant chemotherapy plus radiotherapy.

Reference

1. Keys HM, Bundy BN, Stehman FB, Muderspach LI, Chafe WE, Suggs CL 3rd, Walker JL, Gersell D. Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 1999. 340:1154–1161.

2. Morris M, Eifel PJ, Lu J, Grigsby PW, Levenback C, Stevens RE, Rotman M, Gershenson DM, Mutch DG. Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 1999. 340:1137–1143.

3. Peters WA 3rd, Liu PY, Barrett RJ 2nd, Stock RJ, Monk BJ, Berek JS, Souhami L, Grigsby P, Gordon W Jr, Alberts DS. 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. 2000. 18:1606–1613.

4. Rose PG, Bundy BN, Watkins EB, Thigpen JT, Deppe G, Maiman MA, Clarke-Pearson DL, Insalaco S. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999. 340:1144–1153.

5. Whitney CW, Sause W, Bundy BN, Malfetano JH, Hannigan EV, Fowler WC Jr, Clarke-Pearson DL, Liao SY. 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. 1999. 17:1339–1348.

6. Green JA, Kirwan JM, Tierney JF, Symonds P, Fresco L, Collingwood M, Williams CJ. Survival and recurrence after concomitant chemotherapy and radiotherapy for cancer of the uterine cervix: a systematic review and meta-analysis. Lancet. 2001. 358:781–786.

7. Delgado G, Bundy B, Zaino R, Sevin BU, Creasman WT, Major F. Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol. 1990. 38:352–357.

8. Piver MS, Chung WS. Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma. Obstet Gynecol. 1975. 46:507–510.

9. Benedetti-Panici P, Greggi S, Colombo A, Amoroso M, Smaniotto D, Giannarelli D, Amunni G, Raspagliesi F, Zola P, Mangioni C, Landoni F. Neoadjuvant chemotherapy and radical surgery versus exclusive radiotherapy in locally advanced squamous cell cervical cancer: results from the Italian multicenter randomized study. J Clin Oncol. 2002. 20:179–188.

10. Sardi J, Sananes C, Giaroli A, Bayo J, Rueda NG, Vighi S, Guardado N, Paniceres G, Snaidas L, Vico C, di Paola G. Results of a prospective randomized trial with neoadjuvant chemotherapy in stage IB, bulky, squamous carcinoma of the cervix. Gynecol Oncol. 1993. 49:156–165.

11. Sardi JE, Giaroli A, Sananes C, Ferreira M, Soderini A, Bermudez A, Snaidas L, Vighi S, Gomez Rueda N, di Paola G. Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results. Gynecol Oncol. 1997. 67:61–69.

12. Kigawa J, Minagawa Y, Ishihara H, Itamochi H, Kanamori Y, Terakawa N. The role of neoadjuvant intraarterial infusion chemotherapy with cisplatin and bleomycin for locally advanced cervical cancer. Am J Clin Oncol. 1996. 19:255–259.

13. Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy for locally advanced cervical cancer. A systematic review and meta-analysis of individual patient data from 21 randomised trials. Eur J Cancer. 2003. 39:2470–2486.

14. World Health Organization. WHO handbook for reporting results of cancer treatment. 1979. 48. Geneva: World Health Organization;22–27.

15. Perez CA, Grigsby PW, Nene SM, Camel HM, Galakatos A, Kao MS, Lockett MA. Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer. 1992. 69:2796–2806.

16. Aoki Y, Tomita M, Sato T, Watanabe M, Kase H, Fujita K, Kurata H, Tanaka K. Neoadjuvant chemotherapy for patients younger than 50 years with high-risk squamous cell carcinoma of the cervix. Gynecol Oncol. 2001. 83:263–267.

17. Benedetti-Panici P, Greggi S, Scambia G, Amoroso M, Salerno MG, Maneschi F, Cutillo G, Paratore MP, Scorpiglione N, Mancuso S. Long-term survival following neoadjuvant chemotherapy and radical surgery in locally advanced cervical cancer. Eur J Cancer. 1998. 34:341–346.

18. Eddy GL, Manetta A, Alvarez RD, Williams L, Creasman WT. Neoadjuvant chemotherapy with vincristine and cisplatin followed by radical hysterectomy and pelvic lymphadenectomy for FIGO stage IB bulky cervical cancer: a Gynecologic Oncology Group pilot study. Gynecol Oncol. 1995. 57:412–416.

19. Etcheverry MG, Marantz A, Saine M, Litovska S, Lewi D, Cecchin G, De Pierro AN. Neoadjuvant chemotherapy with cisplatin, ifosfamide and 5-fluorouracil in the treatment of locally advanced cervical cancer. Int J Gynecol Cancer. 2000. 10:53–58.

20. Huang HJ, Chang TC, Hong JH, Tseng CJ, Chou HH, Huang KG, Lai CH. Prognostic value of age and histologic type in neoadjuvant chemotherapy plus radical surgery for bulky (>/=4 cm) stage IB and IIA cervical carcinoma. Int J Gynecol Cancer. 2003. 13:204–211.

21. Hwang YY, Moon H, Cho SH, Kim KT, Moon YJ, Kim SR, Kim DS. Ten-year survival of patients with locally advanced, stage ib-iib cervical cancer after neoadjuvant chemotherapy and radical hysterectomy. Gynecol Oncol. 2001. 82:88–93.

22. Napolitano U, Imperato F, Mossa B, Framarino ML, Marziani R, Marzetti L. The role of neoadjuvant chemotherapy for squamous cell cervical cancer (Ib-IIIb): a long-term randomized trial. Eur J Gynaecol Oncol. 2003. 24:51–59.

23. Paladini D, Raspagliesi F, Fontanelli R, Ntousias V. Radical surgery after induction chemotherapy in locally advanced cervical cancer. A feasibility study. Int J Gynecol Cancer. 1995. 5:296–300.

24. Chang TC, Lai CH, Hong JH, Hsueh S, Huang KG, Chou HH, Tseng CJ, Tsai CS, Chang JT, Lin CT, Chang HH, Chao PJ, Ng KK, Tang SG, Soong YK. Randomized trial of neoadjuvant cisplatin, vincristine, bleomycin, and radical hysterectomy versus radiation therapy for bulky stage IB and IIA cervical cancer. J Clin Oncol. 2000. 18:1740–1747.

25. Lai CH, Hsueh S, Chang TC, Tseng CJ, Huang KG, Chou HH, Chen SM, Chang MF, Shum HC. Prognostic factors in patients with bulky stage IB or IIA cervical carcinoma undergoing neoadjuvant chemotherapy and radical hysterectomy. Gynecol Oncol. 1997. 64:456–462.

26. Benedetti-Panici P, Greggi S, Scambia G, Salerno MG, Amoroso M, Maneschi F, Cutillo G, Caruso A, Capelli A, Mancuso S. Locally advanced cervical adenocarcinoma: is there a place for chemo-surgical treatment? Gynecol Oncol. 1996. 61:44–49.

27. Bolger BS, Symonds RP, Stanton PD, MacLean AB, Burnett R, Kelly P, Cooke TG. Prediction of radiotherapy response of cervical carcinoma through measurement of proliferation rate. Br J Cancer. 1996. 74:1223–1226.