Does adjuvant chemotherapy improve the prognosis of cervical carcinoma with lymph-node metastasis? A long-term follow-up

Objective: to verify the efficacy of adjuvant therapy in the prevention of neoplastic recurrence in patients at high risk for lymph-node involvement on surgical examination.

Methods: 72 patients, suffering from squamous cell cervical carcinoma Stage IB-IIB (FIGO) who underwent radical hysterectomy with lymph-node involvement confirmed at the final histological examination, were enrolled. All the patients were treated with adjuvant chemotherapy (AC), which included cisplatin, bleomycin and vinblastine, and were followed for a minimum period of six years. The results were compared with those obtained with a historical group of 78 patients, with comparable age, stage and lymph-node involvement, on whom only radical surgery (RS) was performed.

Results: the average total survival rate of the two groups (RS + AC vs RS) at five years was 63.9% and 55.1%, respectively (chi2 = 1.191; p = NS). The disease-free interval was 55.6% vs 46.2% (chi2 = 1.324; p = NS). The best results were obtained in cases where the common iliac lymph-nodes were affected, with the highest survival rate of 16.9% in the RS+AC group, out of a total of 25 cases.

Conclusions: adoption of adjuvant chemotherapy in patients at high risk for lymph-node positivity did not produce statistically significant results in terms of overall and disease-free survival; however, a small number of these patients, approximately 9%, could receive benefit from the treatment.

Cervical cancer; Adjuvant chemotherapy; Lymph-node metastasis

[1] Tinga D. J., Timmer P. R., Bouma J., Aalder J. G.: "Prognostic significance of single versus multiple lymph node metastases in cervical carcinoma stage IB". Gynecol. Oncol., 1990, 39, 175.

[2] Martinbeau P., Kjorstad K., Iversen T.: "Stage lb of the cervix: the Norwegian Radium Hospital. Results when pelvic nodes are invol­ved". Obstet. Gynecol., 1982, 60, 215.

[3] Hsu C. T., Cheng Y. S., Su S. C.: "Prognosis of uterine cervical cancer with extensive lymph node metastasis". Am. J. Obst. Gynecol., 1972, 114, 954

[4] Pilleron J., Durand J., Hamelin J.: "Prognostic value of node meta­stasis in cancer of the uterine cervix". Am. J. Obst. Gynecol., 1974, 119, 458.

[5] Inoue T., Morita K.: "The prognostic significance of number of positive nodes in cervical carcinoma stages IB, IIA, and IIIB" Cancer, 1990, 65, 1923.

[6] Lai C. H., Hong J. H., Hsue S., Ng K. K., Chang T. C., Tseng C. J. et al.: "Preoperative prognostic variables and the impact of postoperative adjuvant therapy on the outcomes of stage TB or II cervical carcinoma patients with or without pelvic lymph node metastases. An analysis of 891 cases". Cancer, 1999, 85, 1537.

[7] Byar D. P.: "Identification of prognostic factors". In: Buyse M. E., Staquet M. J., Sylvester R. J., (eds.). Oxford, Oxford University Press, 1984, 423.

[8] Piver M. S., Chung W. S.: "Prognostic significance of cervical lesion size and pelvic node metastases in cervical carcinoma" Obstet. Gynecol., 1975, 46, 507.

[9] Lahousen M., Haas J., Pickel H., Hackl A., Kurz C., Ogris H. et al.: "Chemotherapy versus radiotherapy versus observation for high-risk cervical carcinoma after radical hysterectomy: a rando­mized, prospective, multicenter trial". Gynecol. Oncol., 1999, 73, 196.

[10] Lin H., Chang Chien C. C., Huang E. Y., Eng H. L., Huang C. C. "The role of radical surgery followed by adjuvant therapy for high­risk early-stage cervical carcinoma patients with pelvic lymph node metastasis". Eur. J. Obstet. Gynecol. Reprod. Biol., 2000, 93, 85.

[11] Lin H., Chang Chien C. C., Chang S. Y., Leung S. W.: "Survival advantages and complications of adjuvant therapy in early-stage cervical cancer with pelvic node metastasis". Chang Cung Med., 1998, 21, 383.

[12] Morton G. C., Thomas G. M.: "Does adjuvant chemotherapy change the prognosis of cervical cancer?". Curr. Opin. Obs/et Gynecol., 1996, 8, 17.

[13] Ng H. T., Yuan C. C., Kan Y. Y., Ho E. S. C., Yen M. S., Chao K C.: "An evaluation of chemotherapy in patients with cancer of the cervix and lymph node metastases". Arch. Gynecol. Obstet., 1995, 256, I.

[14] Park R. C., Thigpen J. T.: "Chemotherapy in advanced and recurrent cervical cancer. A review". Cancer (suppl.), 1993, 71, 1446.

[15] Morrow P. C.: "Panel report: is pelvic radiation beneficial in the postoperative management of stage TB squamous cell carcinoma of the cervix with pelvic node metastasis treated by radical hysterectomy and pelvic lymphadenectomy?". Gynecol. Oncol., 1980, 10, 105.

[16] Kinney W. K., Alvarez R. D., Reid G. C., Schray M. F., Soong S J., Moreley G. W.: "Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early stage squamous carcinoma of the cervix with pelvic nodal metastasis: a matched-control study". Gynecol. Oncol., 1989, 34, 258.

[17] Inoue T., Morita K.: "Five-years results of postoperative extended field irradiation on 76 patients with nodal metastases from cervical carcinoma stages 1B to IllB". Cancer, 1988, 61, 2009.

[18] Tanaka Y., Sawada S., Murata T.: "Relationship between lymph node metastases and prognosis in patients irradiated postoperatively for carcinoma of the uterine cervix". Acta Radiol. Oneal., 1984, 23, 455

[19] Morita K., Takagi I., Watanabe M., Kanazawa H.: "Relationship between the radiologic features of esophageal cancer and the local control by radiation therapy". Cancer, 1985, 55, 2668.

[20] Sivanesaratnam Y., Jayalakshmi P.: "Mitomycin C adjuvant chemo therapy after Wertheim's hysterectomy for stage lb cervical cancer". Cancer, 1989, 64, 798.

[21] Lai C.H.,L in TS.,S oongY. K.,C hen S. F.: "Adjuvant chemotherapy after radical hysterectomy for cervical carcinoma". Gynecol Oneal., 1989, 35, 193.

[22] Fuller A. F.,E lliott N.,K osloffC .,L ewis J. L: "Lymph node metastases from carcinoma of the cervix, stage IB and IIA: implications for prognosis and treatment". Gynecol. Oneal., 1982, 13, 265.

[23] Tattersall M. H. N., Ramirez C., Coppleson M.: "A randomized trial of adjuvant chemotherapy after radical hysterectomy in stage IB-IIA cervical cancer patients with pelvic lymph node metastases". Gynecol. Oncol., 1992, 46, 178.

[24] Piver M. S., Rutledge F., Smith J. P.: "Five classes of extended hysterectomy for women with cervical cancer". Obstet. Gynecol., 1974, 44, 265.

[25] Valle G., Napolitano C.: "Lymphadenectomy lombo-pelvica e lymphadenectomy convenzionale: confronto delle sopravvivenze in due serie contemporanee di cervicocarcinomi trattati con Wertheim ed eviscerazione". Atti del 54° Congresso Nazionale della Societa ltaliana di Ostetricia e Ginecologia Milano 16-19 Sett. 1970.

[26] Marzetti L.,G alati G.,F ramarino di Malatesta M. L.,P ecorini F., Marzilli R.: "Stato linfonodale e sopravvivenza in pazienti con cervicocarcinoma". Atti X Congresso Nazionale Societa ltaliana di Ginecologia ed Ostetricia Roma 24-29 Sett. 1986, 107.

[27] Napolitano C. et al.: "Management of invasive cervical carcrnoma: our experience from 1961 to 1979. New trends in Gynecology and Obstetrics". 1986, vol. II, 2.

[28] Levi J. A., Wheeler H. R., Friedlander M., Tattersall M. H. N., Kefford R., Dalley D.: "Dual sequential non-cross resistant chemotherapy for advanced stage squamous cell carcinoma of the cervix". Gynecol. Oneal., 1992, 45, 329.

[29] Sardi J.E.,O f Paola G. R.,C achan A.,C ontreras Ortiz O.,S ananes C.,G iardi A. et al.: "A possibile new trend in the management of the carcinoma of the cervix uteri". Gynecol. Oneal., 1986, 25, 139.

[30] Kinney W. K.,A lvarez R. D.,R eid G. C.,S chray M. F.,S oong S J.,M oreley G. W. et al.: "Value of adjuvant whole-pelvis irradiation after Wertheim hysterectomy for early stage squamous carcinoma of the cervix with pelvic nodal metastasis: a matchedcontrol study". Gynecol. Oneal.,1989, 34, 258.

[31] Mainero C., Napolitano C., Crosara L.: "Gli errori di classificazione del carcinoma della portio". Aggiornamenti in ostetricia e ginecologia, 1972, 5, 200.

[32] Kenter G. G.,H ellebrekers B. W. J., Zwinderman K. H.,V an der Vijver M., Peters L. A. W., Trimbos J. B.: "The case for completing the lymphadenectomy when positive lymph nodes are found during radical hysterectomy for cervical carcinoma". Acta Obstet Gynecol. Scand., 2000, 79, 72.

[33] Samlal R. A. K., Van der Velden J.: "Early cervical carcrnoma: How to manage high-risk patients after radical hysterectomy" Eur. J. of Obstet. and Gynecol. Reprod. Biol., 1999, 85, 137.

[34] Kim D. S., Moon H., Cho S. H.: "Preoperative adjuvant chemotherapy in the treatment of cervical cancer stage IB, IIA, JIB with bulky tumor". Gynecol. Oncol., 1988, 29, 321.

[35] Madha J., Cooke J. K., Flam M., Padmanabhan A., Mawry P. A.； "Preliminary results of concomitant radiotherapy and chemotherapy in advanced cervical carcinoma". Gynecol. Oncol., 1987, 28, 101.

[36] Lahousen M.,P ickelH .,T amussino K.: "Chemotherapy for advanced and/or recurrent cervical cancer". Arch. Gynecol. Obstet., 1987, 240, 247.