LETTERS AND REPLY

Type III radical hysterectomy induction chemotherapyfor patients with locally advanced cervical carcinoma

To the Editor:

I wish to sound caution on the conclusion drawn byLopez-Graniel et al. in their recent publication(1),wherein they expressed optimism on achieving a veryencouraging pathological response rate in pelviclymph nodes following induction chemotherapy. Itwas mentioned in the discussion that in the patientpopulation similar to the one under study, withoutinduction chemotherapy up to 80% of patients wereexpected to have positive nodes. The cited incidenceof node positivity is unrealistic. All three cited refer-ences(2-4) pertained to stage Ib and 2a cervical cancerpatients and the highest incidence of node positivitywas found in a smaller subgroup in the paper byFuller et al.(2) Of 431 patients in stage 1b and 2a, 70patients had greater than 3 cm tumors; of these 44were node positive. It was implied that the combina-tion of cisplatin and gemcitabine by itself must have(my words) sterilized lymph nodes from 80% to amere 17% level. I believe these results are due to un-intentional patient selection.

Lymph node metastasis is related to infiltrativenessof the cervical tumor. A major component of infiltra-tive tumor lies in the parametria and upwards into theuterus. Indeed endometrial extension was associatedwith increased incidence of lymph node positivity asnoted in hysterectomy specimens(5). Recently K. Na-rayan et al.(6) have shown in non-operable cervical can-cer patients 1/8 node positive on PET scan when uter-ine segment was not involved as compared to 15/26node positive patients when lower uterine segmentwas involved with tumor. These infiltrative tumorsare often hypoxic, poorly perfused and do not presenta well-defined tumor margin for accurate measure-ment during examination under anesthesia. Exophytictumors, a major part of which protrudes into the va-gina, are ideal for bi-dimensional measurement. Thesetumors also perfuse well and respond to chemo-therapy very well indeed. Since bi-dimensional mea-surement was essential for consistency, I suggest thatrelatively node negative patients were entered in thistrial. A second selection took place following induc-tion chemotherapy and only those patients had sur-

gery that responded well. Once again less hypoxic andhence relatively node negative patients underwentlymphadenectomy. The remaining nonoperable andhence infiltrative patients were treated with chemoradiation.

Kailash NarayanPeter MacCallum Cancer Institute

Melbourne, Australia

References

1 Lopez-Graniel C, Reyes M, Chanona G, Gonzalez A,Robles E, Mohar A, et al. Type III radical hysterectomyafter induction chemotherapy for patients with locallyadvanced cervical carcinoma. Int J Gynecol Cancer2001;11:210–7.

2 Fuller AF Jr, Elliott N, Kosloff C, Lewis JL Jr. Lymphnodemetastases from carcinoma of the cervix, stages IB andIIA. implications for prognosis and treatment. GynecolOncol 1982;13:165–74.

3 Piver MS, Chung WS. Prognostic significance of cervi-callesion size and pelvic node metastases in cervical car-cinoma. Obstet Gynecol 1975;46:507–10.

4 Van NJ Jr, Donaldson ES, Parker JC, van Dyke AH,Wood EG. The prognostic significance of cell type andlesion size in patients with cervical cancer treated byradical surgery. Gynecol Oncol 1977;5:142–51.

5 Noguchi H, Shiozawa I, Kitahara T, Yamazaki T, FukutaT. Uterine body invasion of carcinoma of the uterine cer-vix as seen from surgical specimens. Gynecol Oncol1988;30:173–82.

6 Narayan K, A McKenzi, D.Bernshaw, R Hicks. the role ofMRIand PET scan in the staging of loco regionally ad-vanced (>1B1) cervical cancer. Radiother Oncol 2001;58:S61.

Response:

We are grateful to Dr Narayan for the comments onour paper “Type III radical hysterectomy after induc-tion chemotherapy for patients with locally advancedcervical carcinoma”(1). We think indeed that our dataare very encouraging on the efficacy of induction che-motherapy for debulking the primary tumor and forsterilization of pelvic lymph nodes. The mentioned80% incidence of positive pelvic nodes seems high butin fact in the study by Fuller et al.(2) the actual figure is

Int J Gynecol Cancer 2002, 12, 232–233

© 2002 IGCS

77% for the subgroup of IB-IIA patients with deepstromal invasion. More recent series in locally ad-vanced unselected patients that undergo surgical stag-ing, node positivity has been found in up to 68% ofpatients(3,4). It is known that the occurrence of lymphnode metastases, not only in cervical but in all malig-nant neoplasms, is the result of biological and ana-tomical factors, many of them not yet known, and itseems unlikely that the infiltrativeness of the cervicaltumor is the sole responsible factor. The Narayan et al.report(5) on 38 patients provides some evidence sup-porting the importance of the involvement of the uter-ine segment for node metastases, which in our studywas not taken into account. However, they also re-lated the tumor volume with the likelihood of loweruterine segment infiltration. Unfortunately we did notestimate the volume of tumors, but we should statethat the mean diameter of them was 5.5 × 6cm whichsuggests that most of our patients had tumor volumesexceeding 60 ml and therefore the bias for selectingpelvic lymph negative patients in our study seemsnonexistent. A more recent study evaluating PET forlymph node staging for untreated cervical carcinomahas shown that 68 (79%) out of 86 patients staged asIB2, IIB and III were positive(6).

Lymph node positivity by no means equals chemo-resistance, hence, the suggestion of a second selectionbias is difficult to support. In fact, in an ongoing studyusing another scheme of induction chemotherapy in acomparable population of patients, we are taking allpatients to surgery regardless of their clinical response(unless they progress during chemotherapy). So far,the first 23 patients have been operated and the pelviclymph node positivity was 21%, which reinforces our“optimism” and encourages us to continue our studies

on induction chemotherapy. In fact, in a nonrandom-ized comparison (submitted for publication) we dem-onstrate that induction chemotherapy followed bysurgery is as effective, in terms of response and sur-vival, as the new standard chemoradiation for locallyadvanced cervical carcinoma patients.

Lopez-Graniel C*Chanona G*

Mohar A*†De la Garza J*

Duenas-Gonzalez A.*†*Instituto Nacional de Cancerologıa e †Instituto deInvestigaciones Biomedicas, UNAM, Mexico City.

References

1 Lopez-Graniel C, Reyes M, Chanona G et al. Type IIIradical hysterectomy after induction chemotherapy forpatients with locally advanced cervical carcinoma. Int JGynecol Cancer 2001;11:210–7.

2 Fuller AF Jr, Elliott N, Kosloff C, Lewis L. Lymph nodemetastases from carcioma of the cervix, stages IB andIIA. implications for prognosis and treatment. GynecolOncol, 1982;13:165–74.

3 Vidaurreta J, Bermudez A, Di Paola G, Sardi J. Laparo-scopic staging in locally advanced cervical carcinoma: anew possible philosophy? Gynecol Oncol 1999;75:366–71.

4 Goff BA, Muntz HG, Paley PJ, Tamini HK, Koh WJ, GreerBE. Impact of surgical staging in women with locallyadvanced cervical cancer. Gynecol Oncol 1999;74:436–42.

5 Narayan K, McKenzie A, Bernshaw D, Hidks R. The roleof MRI and PET scan in the staging of loco-regionallyadvanced (>1B1) cervical cancer. Radiother Oncol2001;58:S61.

6 Grigsby PW, Siegel BA, Dehdashti F. Lymph node stag-ing by positron emission tomography in patients withcarcinoma of the cervix. J Clin Oncol 2001;19:3745–9.

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© 2002 IGCS, International Journal of Gynecological Cancer 12, 232–233