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ORIGINAL RESEARCH |
From the Departments of Obstetrics and Gynecology, and Pathology, Division of Gynecologic Oncology, State University of New York Health Science Center, Brooklyn, New York; and Kings County Hospital, Brooklyn, New York.
Address reprint requests to: Kevin Holcomb, MD, Department of Obstetrics and Gynecology, Beth Israel Medical Center, Petrie Division, First Avenue at 16th Street, New York, NY 10003; E-mail: kholcomb{at}chpnet.org.
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ABSTRACT |
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 ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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METHODS: Fifty-four patients diagnosed by cone biopsy with stage I cervical carcinoma and treated with radical hysterectomy comprised the study group. The association between the depth of invasion on conization, lymph-vascular invasion, positive cone margins, positive endocervical curettage (ECC), and the depth of residual invasion in the radical hysterectomy specimen was examined using Pearson r and point biserial correlation. Independent predictors of the depth of residual invasion were determined by multiple regression.
RESULTS: The depth of residual invasion correlated significantly with the depth of invasion (r = .374) and presence of lymph-vascular invasion (rpb = .372) in the conization specimen, post-cone ECC status (rpb = .669), and age at diagnosis (r = .347). The same factors were jointly assessed using multiple regression (R2 = .636, P< .001). Depth of invasion on conization, lymph-vascular invasion, and ECC status were identified as independent predictors of the depth of residual invasion. Patients with deep (5 mm or greater) stromal invasion and lymph-vascular invasion on conization had significantly higher rates of positive parametrial margins (22% compared with zero, P = .001) and adjuvant radiation (66.7% compared with 20%, P = .004) compared with all other patients.
CONCLUSION: Depth of invasion, presence of lymph-vascular invasion, and age at diagnosis were independent predictors of the depth of residual invasion in the subsequent hysterectomy specimen. These factors should be considered in treatment planning. Patients with a combination of these factors may have increased risk for deep residual invasion, positive hysterectomy margins, and adjuvant radiation.
Radical hysterectomy has been used in the treatment of stage I cervical cancer with relative success, providing an 85% chance of 5 year survival.1,2 Unfortunately, there remains a population of patients who will ultimately fail surgical treatment, and the mortality after surgery has remained unchanged over the last three decades.3
Previous studies have identified adverse prognostic indicators for stage I cervical cancer that are independently associated with tumor recurrence and decreased survival. These factors, which are diagnosed at the time of radical hysterectomy and pelvic lymphadenectomy, include pelvic and para-aortic lymph node metastases,4,5 positive surgical margins, and primary tumor-related factors such as deep stromal invasion6 and lymph-vascular space invasion.7
Cervical conization before radical hysterectomy provides an opportunity for a preoperative assessment of tumor invasiveness. This assessment may be helpful in estimating the risk of poor prognostic factors and determining the mode of treatment. The purpose of the current study was to determine if there is a significant correlation between cervical cone biopsy and pathologic findings at radical hysterectomy in patients with stage I cervical cancer.
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MATERIALS AND METHODS |
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ABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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All slides of the conization specimens were reviewed by two of the authors (TMD and ADN) with special attention given to the presence of lymph-vascular space invasion, depth of stromal invasion, margin status, and postconization endocervical curettage (ECC) status. The depth of invasion in the conization specimen was recorded in millimeters, whereas the depth of residual invasion was recorded in millimeters and fractional thirds (ie, inner, middle, and outer third stromal invasion). The association between the depth of residual invasion and these cone biopsy factors was examined using Pearson r and point biserial correlation.8 The point biserial correlation (rpb) is equivalent to the Pearson product moment correlation between two variables where one is dichotomous and the other is continuous. A linear regression model was created using cone biopsy measures to determine which factors are predictors of the depth of residual invasion. Additionally, patients with deep stromal invasion (5 mm or greater) and lymph-vascular space invasion on conization were then compared with all other patients, using 
2 analysis, with regard to hysterectomy margins, nodal status, and the rate of adjuvant radiation. Statistical Package for the Social Sciences (Chicago, IL) software was used for all statistical analyses.
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RESULTS |
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. The mean age was 48.3 years. No patient had a gross cervical lesion and the mean size of the cervix was 3.1 cm (range 1–5 cm). Forty-four squamous cell carcinomas (81.5%), four adenocarcinomas (7.4%), two adenoid basal carcinomas (3.7%), and four tumors of other histologic types (7.4%) were diagnosed.
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After radical hysterectomy, 19 patients had no residual tumor detected. Inner, middle, and outer third residual stromal invasion was seen in 13 patients, nine patients, and 13 patients, respectively. Lymph-vascular space invasion was detected in 11 (20%) hysterectomy specimens, and the parametrial margins were positive for carcinoma in two patients (3.7%). Three women had positive pelvic nodes (5.6%) and a para-aortic metastasis was found in one patient (2%).
Fifteen patients (27.8%) had poor prognostic indicators diagnosed on radical hysterectomy and received adjuvant pelvic radiation. The indications for adjuvant treatment included a combination of outer third residual stromal invasion and lymph-vascular space invasion (five patients), outer third residual stromal invasion alone (four patients), positive nodes (four patients), and positive surgical margins (two patients).
We examined the association between depth of invasion on conization, presence of lymph-vascular space invasion in the cone specimen, status of the post-cone ECC, age at presentation, and the presence of vaginal spotting at diagnosis with the depth of residual invasion using Pearson r and point biserial correlation. The depth of residual invasion was found to be significantly correlated with depth of invasion (r = .374, P = .005) and presence of lymph-vascular space invasion (rpb = .372, P = .006) in the conization specimen, post-cone ECC status (rpb = .669, P < .001), and age at diagnosis (r = .347, P = .01). The correlation between the depth of residual invasion and the presence of vaginal spotting approached significance (rpb = .262, P = .055).
To examine jointly the association between these factors and the depth of residual invasion we created a linear regression model. The coefficient of determination (R2) was .636 (F5,37 = 12.928, P < .001). The results of the multiple linear regression are presented in Table 2. Depth of invasion on conization, presence of lymph-vascular space invasion, and post-cone ECC status were found to be significant predictors of the depth of residual invasion.
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2 analysis. Parametrial margins were positive in two of nine women (22%) in group 1, whereas all 45 women in group 2 had negative margins (2 = 10.38, P = .001). Outer third residual stromal invasion was found in six women (66.7%) in group 1 and seven women (15.6%) in group 2 (2 = 10.72, P = .001). There was a trend toward increased lymph node metastases in group 1 (22%) compared with group 2 (4.4%), however statistical significance was not reached (2 = 3.46, P = .06). The rates of adjuvant radiation given for the above-stated indications were then compared between the groups. Group 1 had a significantly increased rate of adjuvant radiation (66.7% compared with 20%) compared with group 2 (2 = 8.14, P = .004). This difference remained statistically significant when cone biopsies with nonsquamous histologies were excluded (47% compared with 16%, P = .02). |
DISCUSSION |
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Based on clinical presentation, the patient population of the current study may be considered at low risk for adverse prognostic indicators and excellent candidates for radical hysterectomy. No patient had a visible cervical lesion and the mean size of the cervix was 3.1 cm. Twenty-eight percent of the patients, however, had poor prognostic factors including positive nodes, positive margins, outer third residual stromal invasion, and a combination of deep residual invasion and lymph-vascular space invasion documented by radical hysterectomy.
Because of the retrospective nature of this review, adjuvant radiation was offered to the study population in a subjective manner. This is a reflection of institutional policy and does not imply that each indication was appropriate. Several authors, however, have recommended adjuvant pelvic radiation after radical hysterectomy in patients with poor prognostic factors such as positive nodes, positive margins, deep stromal invasion, and lymph-vascular space invasion to improve local control.7,9–11 Sedlis et al, in a recent Gynecologic Oncology Group study, documented a 47% reduction in the risk of recurrence in patients receiving adjuvant pelvic radiotherapy for large tumor size, deep stromal invasion, and lymph-vascular space invasion.12
Because of the increased risk of poor prognostic factors seen in patients with deep stromal invasion and lymph-vascular space invasion on conization, 66% of patients with 5 mm or greater stromal invasion and lymph-vascular space invasion received adjuvant radiation after radical hysterectomy, compared with only 20% of all other patients.
Radical hysterectomy and pelvic irradiation have been found to be of equivalent efficacy in the treatment of stage I cervical cancer.13,14 The choice of treatment modality for stage I disease is usually based on the risk of comparative morbidity. Surgery has been preferred in young women because of increased rates of ovarian preservation15 and because many surgeons believe sexual dysfunction is more prevalent after radiation therapy.16 These benefits of radical hysterectomy, however, are not applicable to patients who ultimately receive postoperative radiation. Anderson et al reported only four of 24 (17%) patients who received postoperative radiation maintained ovarian function despite ovarian transposition.15 Alterations in sexual function are also reported to be more pronounced in patients receiving a combination of pelvic surgery and radiation than either radiation or operation alone.17 In addition, the rate of enteric complications after a combined modality approach may be higher than primary irradiation alone. Barter et al documented complications, such as obstruction, fistula, and dysfunction, in 30% of patients treated with radical hysterectomy and pelvic radiation.18 The incidence of major complications from primary irradiation for stage I cervical cancer has been reported to be 3–5%.19
The increased rate of complications observed in patients treated with both radiation and surgery has not been associated with an improvement in clinical outcome. Previous studies have shown no significant difference in tumor control or survival in patients with squamous cell carcinoma treated with a combination of radiation and surgery compared with irradiation alone.20,21 Therefore, the likelihood of adjuvant radiation after radical hysterectomy should be considered when selecting a treatment modality.
Our data indicate that cone biopsy parameters are helpful in estimating the risk of residual stromal invasion, surgical margin status, and possibly lymph node metastases. In our institution, patients with depth of invasion of 5 mm or greater and lymph-vascular space invasion on conization had a significantly increased rate of adjuvant radiation compared with all other patients. Larger studies with standardized indications for adjuvant radiation are necessary to confirm these findings.
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Footnotes |
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Received January 31, 2001. Received in revised form June 18, 2001. Accepted June 28, 2001.
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REFERENCES |
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2. Artman LE, Hoskins WJ, Bibro MC, Heller PB, Weiser EB, Barnhill DR, et al. Radical hysterectomy and pelvic lymphadenectomy for stage IB carcinoma of the cervix: Twenty-one years’ experience. Gynecol Oncol 1987;28:8–13.[Medline]
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14. Newton M. Radical hysterectomy or radiotherapy for stage I cervical cancer. Am J Obstet Gynecol 1975;123:535–42.[Medline]
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18. Barter JF, Soong SJ, Shingleton HM, Hatch KD, Orr JW Jr. Complications of combined radical hysterectomy-postoperative radiation therapy in women with early stage cervical cancer. Gynecol Oncol 1989;32:292–6.[Medline]
19. Kottmeier HL. Complications following radiation therapy in carcinoma of the cervix and their treatment. Am J Obstet Gynecol 1964;88:854–61.[Medline]
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| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
