The value of squamous cell carcinoma antigen in patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy Giovanni Scambia, MD, Pierluigi Benedetti Panici, MD, Gabriela Baiocchi, MD, Mariangela Amoroso, MD, Elvira Foti, MD, Stefano Greggi, MD, and Salvatore Mancuso, MD Rome, Italy Serum levels of squamous cell carcinoma antigen were measured in 688 samples from 119 patients with cervical cancer. Ninety-seven patients had primary tumors and 22 had recurrent disease. Serum samples were obtained before each cycle of chemotherapy, before surgery, at least 4 weeks after surgery, and at 2- to 3-month intervals during follow-up from 78 of the patients with locally advanced cervical cancer who were receiving neoadjuvant chemotherapy. Squamous cell carcinoma antigen serum levels were elevated (>2.5 ng/ml) in 71% of the patients with primary tumors and in 77% of the patients with recurrent carcinomas. The percentage of positivity increased significantly with stage (p = 0.03) and was higher in squamous cell tumors than in adenocarcinomas (p < 0.001). Pretreatment squamous cell carcinoma antigen levels were not predictive of neoadjuvant chemotherapy response; however, the serial measurement during chemotherapy showed a good correlation with clinical response. In the patients who had surgery, squamous cell carcinoma antigen positivity did not correlate to pathologic findings (lymph node status, cervical and parametrial infiltration). Disease-free survival was significantly longer in patients with squamous cell carcinoma antigen pretreatment values that were lower than 5 ng/ml, compared with patients with marker higher than 5 ng/ml (p < 0.01). Abnormal squamous cell carcinoma antigen serum levels preceded the clinical detection of recurrence in eight of 11 patients with a median lead time of 5 months. (AM J OBSTET GVNECOL 1991;164:631-6.)

Key words: Squamous cell carcinoma antigen, cervical cancer, tumor markers, gynecologic malignancies

The management of patients with cervical cancer is hindered by limitations in clinical staging, assessment of response to therapy, and early detection of tumor recurrence. The identification of sensitive tumor markers may overcome these difficulties by permitting a more timely alternative or additional therapy. Squamous cell carcinoma antigen, a subfraction of the TA-4 antigen, appears to be the most promising of the tumor markers that have been proposed for cervical cancer. ,·9 Although squamous cell carcinoma antigen is not useful for the early diagnosis of cervical cancer,'·9 recent data demonstrate that in patients with invasive disease, this antigen could be employed in monitoring the response to therapy6.9 as well as in detecting recurrences. 5 . 9 However, until now, only few data are available on the serial measurements of the antigen over long periods of time in a large population of patients. From the Department of Gynecology, Catholic University. Received for publication June 7, 1990; revised August 27, 1990; accepted August 31,1990. Reprint requests: Salvatore Mancuso, MD, Department of Gynecology, Catholic University, Largo A. Gemelli, 8, 00168-Roma, Italy.

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In particular, only a few anecdotal cases have been reported concerning squamous cell carcinoma antigen evaluations during chemotherapy.6.s Moreover, in spite of a previous paper by Kato et al.,10 which suggests that TA-4 might have a prognostic significance in cervical cancer, no other studies have addressed this point. Therefore the exact role of squamous cell carcinoma antigen in the proper management of patients with cervical cancer is still to be assessed. We report here the experience of the Department of Gynecology of the Catholic University in the measurement of squamous cell carcinoma antigen in patients with invasive cervical cancer. Our study focuses on a large group of patients with locally advanced disease who had neoadjuvant chemotherapy followed by radical surgery'l. '2 and in whom squamous cell carcinoma antigen serum levels were serially measured for a period of 5 to 48 months. The data were analyzed to highlight the following points: (I) to determine whether squamous cell carcinoma antigen is an indicator of chemosensitivity and whether serial measurements of the antigen are a useful tool in monitoring the response to chemotherapy; (2) to ascertain whether 631

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February 1991 Am J Obstet Gyneco1

Table I. Pretreatment squamous cell carcinoma antigen serum levels according to different variables

sec (ng/ml) >2.5 No. of serum samples tested

Normal subjects Primary tumor Stage I Stage II Stage III Stage IV TOTAL

Recurrence Histologic type Squamous Adenocarcinoma Grade 1 2 3

No.

I

>5

%

No.

I

%

Median

1.5