Close Vaginal Margins as a Prognostic Factor after Radical Hysterectomy

Share Embed


Descrição do Produto

GYNECOLOGIC ONCOLOGY ARTICLE NO.

68, 229 –232 (1998)

GO984960

Close Vaginal Margins as a Prognostic Factor after Radical Hysterectomy Ricardo E. Estape, M.D., Roberto Angioli, M.D., Marilu Madrigal, M.D., Mike Janicek, M.D., Carmen Gomez, M.D.,* Manuel Penalver, M.D., and Hervy Averette, M.D. Department of Gynecologic Oncology and and *Department of Pathology, University of Miami/Jackson Memorial Hospital, Miami, Florida 33136 Received July 31, 1997

be a superficially spreading tumor with minimal invasion but close resection margins. There have been no large series on close vaginal margins reported, most likely secondary to their low incidence. This review looks at the 30-year experience in an academic center to evaluate close vaginal margins.

From 1965 to 1995, at the University of Miami/Jackson Memorial Medical Center, 1223 patients with stage IA2, IB, or IIA cervical cancer have undergone a radical hysterectomy. The charts of these patients were reviewed retrospectively for pathology reports showing positive or close surgical margins. Fifty-one of these cases had final pathology results interpreted as close vaginal margins (CVM), which we define as tumor less than or equal to 0.5 cm from the vaginal margins of resection. All slides of blocks with close vaginal margins were found and reviewed by a single pathologist. Twenty-eight (54.9%) had parametrial involvement or positive lymph nodes and received adjuvant radiation therapy (RT). Of the remaining 23 cases, only 6 had other high risk factors, tumor greater than 4 cm, poorly differentiated, greater than 50% invasion, or lymphovascular space involvement. Sixteen of 23 received radiation. The 5-year survival was significantly greater with RT, 81.3%, than without RT, 28.6% (P < 0.05). The recurrence rate was also decreased from 85.7 to 12.5% (P < 0.01). Although present in less than 2% of radical hysterectomy specimens, CVM without other high risk factors may be an important prognostic variable that should be considered when making adjuvant therapy decisions. © 1998 Academic Press

MATERIALS AND METHODS

INTRODUCTION

From 1965 to 1995, 1223 radical hysterectomies with pelvic and para-aortic lymphadenectomy were performed by the Division of Gynecologic Oncology at the University of Miami/Jackson Memorial Medical Center. Eligible patients were obtained from a computerized cervical cancer database at the University of Miami. Inclusion criteria were patients with clinical stages IA2, IB, or IIA as defined by the International Federation of Gynecology and Obstetrics who underwent a radical hysterectomy with pelvic and paraaortic lymphadenectomy. All patients underwent the Wertheim–Meigs radical hysterectomy with or without the Miami modifications as described by Hoskins [13]. An extended pelvic and para-aortic lymphadenectomy to the level of the third portion of the duodenum or the inferior mesenteric artery was performed as part of the surgical procedure. All histologic slides confirming the diagnosis of invasive cervical cancer and close vaginal margins were reviewed by the Department of Pathology at the University of Miami at the time of surgery and reviewed prior to study entry by a single pathologist. Histologic grade, lymph node status, tumor size, capillary–lymphatic space involvement, and distance from surgical margins were reported and reviewed. It has been standard protocol for the Department of Pathology at the University of Miami to report surgical margins as free of tumor, tumor involving margins, or margins free but tumor extending to within 1 cm of the margins during the study period. It has also been protocol to take extended sections of the margins when tumor is seen close to the surgical margins to rule out the presence of tumor at the margins. All slides of patients with reported close vaginal margins were reviewed and confirmed.

Many reports have correlated 5-year survival rates in cervical cancer patients with specific surgical–pathological factors in an attempt to determine characteristics associated with poor prognosis [1–12]. Factors such as depth of invasion, parametrial involvement, capillary–lymphatic space invasion, tumor grade, involvement of surgical margins, and tumor size have been evaluated. The data for these factors have been strong enough that a surgical staging system has been proposed that may further subdivide patients into more accurate prognostic groups. In this review, the significance of close vaginal margins, defined as tumor within 0.5 cm of the vaginal margins of resection, is reviewed in terms of correlation with other surgical–pathological factors and effects of adjuvant radiation therapy on long-term survival. The focus of this review is to evaluate those patients with close vaginal margins in the absence of other high risk factors. The characteristic tumor would 229

0090-8258/98 $25.00 Copyright © 1998 by Academic Press All rights of reproduction in any form reserved.

230

ESTAPE ET AL.

FIG. 1.

Kaplan–Meier cumulative survival plot for radiated versus nonradiated patients.

The charts for these 51 patients were reviewed and the relevant data plus demographic data and surgical complications were recorded. The 5-year survival and recurrence data were compiled from the chart, from direct patient contact, or from the Jackson Memorial Hospital Tumor Registry, which follows these patients annually via phone or written contact. All patients that received postoperative radiation therapy underwent AP–PA opposed fields with 25 MV photons using either a betatron or a linear accelerator. Patients also received vaginal brachytherapy via either ring applicator, cylinder applicator, or interstitial needles. Radiation therapy was given with standards appropriate for the year treated. Some patients were treated at the University of Miami but the majority were treated at other radiation centers. All patients received a minimum dose of 5040 cGy with the majority receiving 5500 – 6000 cGy to the pelvis. No whole abdominal radiation or extended field radiation was used in these patients. The associations between close vaginal margins and other variables of interest were analyzed by the x2 and student’s t test. An interrelation between variables was defined as an association at the 0.05 significance level. Survival analysis was done using censored data on a Kaplan–Meier survival plot (Fig. 1). Multivariate unconditional logistic regression analyses were done to identify independent risk factors for recurrence.

All analyses were done using Statistix software package (Analytical Software; Tallahassee, FL). RESULTS From July 1965 to December 1995, 1223 patients underwent radical hysterectomy and extended lymphadenectomy as described by Hoskins for early stage, IA2, IB, and IIA cervical carcinoma [13]. Fifty-one were confirmed to have close vaginal margins. Any patients with positive vaginal or other margins were excluded. For this group of patients, mean operating time was 3.1 h (range 2– 6 h). Mean blood loss was 1440 cc (range 300 –2500 cc) with autologous harvesting of intraperitoneal blood for autotransfusion used in 26 of the 51 cases. Mean hospital stay was 6 days (range 4 –24 days). Patients ranged from 21 to 70 years of age with a mean of 52.5 years. Sixty percent were within the ages of 40 and 60. Twenty-eight of 51 were Caucasian (54.9%), 13 were African-American (25.5%), and 10 were Hispanic (19.6%). A total of 28 of the 51 patients had positive pelvic and/or para-aortic nodes and were treated with adjuvant radiation therapy. The 5-year survival rate for this group was 57.9% (11 of 19) if only pelvic nodes were involved and 33.3% (3 of 9) if para-aortic nodes were involved.

231

CLOSE VAGINAL MARGINS

Twenty-three had negative lymph nodes and were further reviewed for other significant risk factors. All 23 had squamous cell carcinomas. Six of these 23 patients had one or more of the following risk factors: tumor greater than 4 cm (2 of 6), poorly differentiated (1 of 6), positive lymphovascular space involvement (2 of 6), and greater than 50% cervical stromal invasion (3 of 6). None were stage IA2, 6 were IB1 (26.1%), 2 were IB2 (8.7%), and 15 were IIA (65.2%). None of the patients had microscopically involved parametria. Sixteen of the 23 (69.6%) with close vaginal margins received adjuvant radiation therapy (RT), including the 6 with high risk factors. The 5-year survival was 81.3% (13 of 16) with adjuvant RT and 28.6% (2 of 7) without adjuvant RT. Recurrence rates were 12.5% (2 of 16) in the radiated group and 85.7% (6 of 7) in the nonradiated group. In the radiated group, 1 recurred centrally at 18 months, underwent a total pelvic exenteration, and is alive with no evidence of disease at 6 years. The other patient recurred at 14 months both centrally and to the lungs and received chemotherapy, cisplatin-based, but died 3 years after initial surgery. In the nonradiated group, 6 of 7 recurred. All recurrences occurred within 15 months, with a mean of 8 months, not statistically different from the radiated group. All had central recurrence and 4 had distant recurrence as well. The 2 with local recurrence received RT but 1 recurred and underwent a total pelvic exenteration but died within 5 years of initial diagnosis; the other is still alive at 11 years. The 4 with distant recurrence had cisplatin-based chemotherapy and 2 had RT for palliation to the pelvis, but all have died within 5 years. Using logistic regression to show variables independently associated with recurrence and decreased 5-year survival showed nonsignificant values. Control cases were selected to correlate with age, stage, histologic type, and year of diagnosis. Independence for close vaginal margins could not be established (P 5 0.13) with the 23 patients that were included in the study.

for patients with CVM was comparable to the survival rates of patients with positive surgical margins and positive pelvic nodes [1]. The Gynecologic Oncology Group (GOG) has shown that while histologic grade, depth of invasion, parametrial extension, and capillary–lymphatic space involvement are significant predictors of pelvic node metastasis, age, tumor size, histologic type, uterine extension, and pelvic washings are not [2, 3]. Our data confirmed the findings of the GOG and other authors but also raise concern for those patients found to have CVM without other risk factors. Another significant finding was that 65% of these patients were stage IIA and as such probably had inadequate margins of resection. Routine frozen section margins are not done but strong consideration should be given to frozen section margins in all IIA lesions. However, 35% of these patients were not stage IIA and still had CVM. This may suggest that frozen margins should be considered for all radical hysterectomies. Even though the incidence is low, the consequences of CVM are dire for the patient. Adjuvant radiation therapy in these patients with CVM increased the 5-year survival from 28.6 to 81.3%. The recurrence rates were similarly decreased in those patients receiving adjuvant radiation therapy from 85.7 to 12.5%. Although the number of patients is not significant, there is a concern regarding the prognosis for these patients. If we exclude those patients with high risk factors, 75% of those patients with CVM would not receive adjuvant therapy based on current standards of practice. It therefore seems prudent that CVM be considered a significant surgical pathological factor and those patients with this finding should be offered adjuvant radiation therapy. From our study, it appears that close vaginal margins is an important prognostic factor and should be treated with adjuvant radiation therapy in the absence of other surgical–pathological factors. Further clinical studies are indicated.

REFERENCES DISCUSSION Since the original description of radical hysterectomy for the treatment of early cervical carcinoma [14, 15], many attempts have been made to characterize patients that benefit from radical surgery as well as those that may require adjuvant therapy. Characteristics such as histologic grade, depth of invasion, parametrial extension, lymph nodes, and capillary– lymphatic space involvement have all been addressed [1–12]. One factor not previously addressed is the issue of close vaginal margins (CVM). The data presented here suggest that patients with CVM have a poorer prognosis, decreased 5-year survival, and an increased recurrence rate when compared to patients with margins greater than 0.5 cm. Even when removing patients with other high risk factors, CVM shows a tendency to have poorer prognosis. The 5-year survival rate and recurrence rate

1. Averette HE, Nguyen HN, Donato DM, Penalver MA, Sevin BU, Estape RE, Little WA: Radical hysterectomy for invasive cervical cancer: a 25-year prospective experience with the Miami technique. Cancer 71: 1422–1437, 1993 2. Delgado G, Bundy BN, Fowler WC, Stehman FB, Sevin BU, Creasman WT, Major F, DiSaia P, Zaino R: A prospective surgical pathological study of stage I squamous carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 35:314 –320, 1989 3. Delgado G, Bundy BN, Zaino R, Sevin BU, Creasman WT, Major FU: 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 38:352–357, 1990 4. Sevin BU, Nadji M, Averette HE, Hilsenbeck S, Smith D, Lampe B: Microinvasive carcinoma of the cervix. Cancer 70:2121–2128, 1992 5. Sevin BU, Method MW, Nadji M, Lu Y, Averette HE: Small cell carcinoma of the cervix treated with radical hysterectomy. Cancer 77:1489 – 1493, 1996 6. Steren A, Nguyen HN, Averette HE, Estape RE, Angioli R, Donato DM:

232

7.

8.

9.

10.

ESTAPE ET AL.

Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience. Gynecol Oncol 48:355–359, 1993 Harrison TA, Sevin BU, Koechli O, Nguyen HN, Averette HE, Penalver MA: Adenosquamous carcinoma of the cervix: prognosis in early stage disease treated by radical hysterectomy. Gynecol Oncol 48:310 –315, 1993 Sevin BU, Nadji M, Lampe B, Lu Y, Hilsenbeck S, Koechli O: Prognostic factors in early stage cervical carcinoma treated with radical hysterectomy. Cancer 76:1978 –1986, 1996 Haas J, Friedl H: Operative Treatment of Cervical Cancer, in Burghard E, Monaghan JM (eds): Bailliere’s Clinical Obstetrics and Gynecology. Eastborne, Bailliere Tindall, 1988, pp 829 – 837 Gauthier P, Gore I, Shingleton HM: Identification of histopathologic risk groups in stage IB squamous cell carcinoma of the cervix. Obstet Gynecol 66:569 –574, 1985

11. Kamura T, Tsukamoto N, Tsuruchi N, Saito T, Matsuyama T, Akazawa MS: Multivariate analysis of the histopathologic prognostic factors of cervical cancer in patients undergoing radical hysterectomy. Cancer 69: 181–186, 1992 12. Sevin BU, Lu Y, Bloch DA, Nadji M, Koechli OR, Averette HE: Surgically defined prognostic parameters in patients with early cervical carcinoma: a multivariate survival tree analysis. Cancer 78:1438 –1446, 1996 13. Hoskins WJ, Ford JH, Lutz MH, Averette HE: Radical hysterectomy and pelvic lymphadenectomy for management of early invasive cancer of the cervix. Gynecol Oncol 4:278 –290, 1976 14. Meigs JV: Carcinoma of the cervix: the Wertheim Operation. Surg Gynecol Obstet 78:195–199, 1944 15. Bonney V: The treatment of carcinoma of the cervix by Wertheim’s operation. Am J Obstet 30:815– 830, 1935

Lihat lebih banyak...

Comentários

Copyright © 2017 DADOSPDF Inc.