Chemotherapy as initial treatment for cervical carcinoma: clinical and tumor marker response.

Chemotherapy was given as initial therapy to 23 patients with previously untreated early and advanced cervical carcinoma. A combination of cisplatin and VP-16 was given in squamous cell carcinoma, and cisplatin, epirubicin and cyclophosphamide in adenocarcinoma in one to three courses at 4-week intervals. The overall clinical response rate to initial chemotherapy was 78% (80% in early and 78% in advanced disease). A complete response was achieved in 3 (13%) and a partial response in 15 (65%) patients. To obtain independent information on treatment response serial tumor marker determinations were used in patients with elevated pretreatment levels. Squamous cell carcinoma antigen (SCC) responded to chemotherapy by decreasing levels in 91% of the cases, carcinoembryonic antigen (CEA) in 33%, CA 125 in 83%, and tumor-associated trypsin inhibitor (TATI) in 50%, respectively. These results show that cervical carcinoma is a drug-responsive tumor and that SCC and CA 125 can be used as an aid in the evaluation of response to chemotherapy. Initial chemotherapy appears be of value by reducing tumor volume thus providing better conditions for surgery and radiotherapy.     

Squamous cell carcinoma (SCC) antigen in patients with invasive cervical carcinoma during primary irradiation

In a prospective study, serum concentrations of squamous cell carcinoma (SCC) antigen were determined by radioimmunoassay from 74 healthy volunteers and 54 patients with cervical carcinoma who underwent irradiation therapy. 5.4% of the controls had SCC levels greater than 3.0 ng/ml, which was considered as upper limit of the normal range. 31/54 (57.4%) patients and 60% of the patients with SCC had elevated pretreatment levels. In all patients with pretreatment serum levels above 3.0 ng/ml, SCC serum levels decreased during irradiation therapy. 4/5 patients with posttreatment levels greater than 0.5 ng/ml developed recurrence or persistence of tumor, 1 patient could not be followed up. Good conformity was found between SCC antigen serum levels and therapy response. SCC antigen determinations during and after therapy provide a useful tool in detecting progression and persistence of tumor.     

Serum squamous cell carcinoma antigen levels in women with neoplasms of the lower genital tract and in healthy controls

Summary Squamous cell carcinoma antigen levels in 74 healthy volunteers, 57 patients with CIN and 91 patients with cervical carcinoma were determined by radioimmunoassay. 5.4% of healthy volunteers were above and all patients with CIN were below 3.0 ng/ml. 63.1% of 65 patients with primary squamous cell carcinoma, 1 out of 7 adenocarcinomas and 68.4% of 19 patients with recurrence of squamous cell carcinoma of the cervix had elevated SCC antigen levels. Elevated posttreatment levels carried a high risk factor of tumor persistence. Increases in SCC antigen levels during follow up usually signified recurrent carcinoma.     

Value of squamous cell carcinoma antigen levels in invasive cervical carcinoma

Squamous cell carcinoma (SCC) antigen (Ag) levels were measured by radioimmunoassay in 64 patients with invasive squamous cell cervical carcinoma and 9 patients with nonsquamous carcinoma before the initiation of treatment. The mean antigen level in the squamous group was 10.5 ng/ml compared with 1.3 ng/ml in the nonsquamous group. In the patients with squamous cell carcinoma, mean SCC Ag level correlated well with stage, except for bulky stage IB tumors (P less than 0.05), where mean level was much higher than expected. Patients with exophytic tumors had significantly higher SCC Ag levels than those with nonexophytic tumors. Follow-up on 62 evaluable patients ranged from 20 to 40 months. The mean pretreatment SCC Ag level for patients free of disease at last contact was 5.6 ng/ml, in contrast to 16.1 ng/ml for those with recurrent disease. Only 32% of patients free of disease had pretreatment levels of 4.0 ng/ml or greater, while 86% of those with recurrent disease had such values (P less than 0.05). Forty patients had follow-up samples drawn 1 to 14 months after treatment. Mean post-treatment SCC Ag levels dropped to 1.8 ng/ml in 21 patients free of disease (73% decrease), but remained elevated at 13.4 ng/ml (17% decrease) in 19 patients with recurrences. The specificity of follow-up SCC Ag levels as a predictive test for outcome was 90%, with a sensitivity of 63%. We conclude that pretreatment SCC Ag levels correlate well with tumor stage, lesion morphology, and extent of disease. SCC antigen levels may be used to follow patients to determine effectiveness of treatment.     

A clinical study on multiple tumor markers following therapy in patients with uterine cervical carcinoma

In order to evaluate the clinical significance of multiple tumor markers, plasma levels of carcino-embryonic antigen (CEA), squamous cell carcinoma-related antigen (SCC), tissue polypeptide antigen (TPA) and immunosuppressive acidic protein (IAP) were measured before and after treatment in 136 patients (89 surgery cases and 47 radiotherapy cases). The patients had invasive cervical carcinoma (stages I-IV). The effect of radiotherapy was examined by cytology and biopsies obtained by colposcopy. For CEA, SCC and TPA there was a significant reduction (p less than 0.01) in values between the pretreatment and posttreatment periods, but plasma IAP was transiently increased after operation. Cytology and histology revealed negative rates of 95.6% and 86.7%, respectively, after radiotherapy. Regarding recurrence, for the negative groups and positive groups plasma CEA, SCC, TPA and IAP were determined in 24 patients with stage IIIb before radiotherapy. Only the CEA concentration showed a good correlation with the outcome (p less than 0.01). Effective serial plasma determinations of CEA, SCC and TPA in patients with cervical carcinoma following therapy may often be useful in the evaluation of therapy as well as in the earlier detection of recurrent disease.     

Clinical significance of squamous cell carcinoma antigen in cancer of the human uterine cervix. Comparison with CEA and CA-125.

Serum squamous cell carcinoma antigen (SCCa) concentrations were determined by a radioimmunoassay kit before and during the treatment of 50 patients with cervical carcinoma: 44 with squamous cell carcinoma (SCC) and 6 with adenocarcinoma. The positivity rate of SCCa was 50% (52% for SCC and 33% for adenocarcinoma). The sensitivity of SCCa for SCC was twice as high as that of CEA and CA-125. Low serum concentrations were observed in early-stage carcinoma, indicating that SCCa is not useful for diagnosis. In advanced cases, serum levels were directly and significantly correlated with the stage of the disease.     

Comparison between squamous cell carcinoma-associated antigen and CA-125 in patients with carcinoma of the cervix

Serum levels of CA-125 and squamous cell carcinoma-associated antigen (SCC) were measured in 30 patients with squamous cell carcinoma and 12 patients with adenocarcinoma of the uterine cervix. SCC was elevated in 67% of patients with squamous cell carcinoma but in only 25% of patients with adenocarcinoma. In contrast, CA-125 was elevated in 75% of patients with adenocarcinoma but in only 26% of patients with squamous cell carcinoma. These data demonstrate the applicability of the measurement of CA-125 as a tumor marker for cervical adenocarcinoma and confirm the value of the measurement of SCC antigen in patients with cervical squamous cell carcinoma. Moreover, we show that measurement of SCC antigen in adenocarcinoma and measurement of CA-125 in squamous cell carcinoma are of insufficient clinical value.     

Squamous cell carcinoma antigen: pretreatment levels as an indicator of advanced or metastatic disease

Pretreatment values of squamous cell carcinoma antigen (SCC) were obtained in 100 consecutive patients with squamous cell carcinoma of the cervix presenting to the Regional Gynaecological Oncology Centre in Gateshead, UK. Nine patients deemed to have locally advanced disease not suitable for primary surgery had elevated levels. Ninety-one patients were suitable for primary surgery. Sixty-seven had normal SCC levels, two of which had lymph node metastases. Twenty-four had elevated SCC levels, 14 of which had lymph node metastases. Two early recurrences have been detected in the raised SCC group where no lymph node metastases were present. Elevated levels of SCC in the pretreatment assessment indicate a high risk of lymph node metastases and of developing recurrent disease after primary surgery.     

Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix

In this study, squamous cell carcinoma antigen (SCC) was detected in 96 of 157 patients with squamous cell carcinoma of the cervix and the percentage of patients with raised SCC levels increased with the stage of disease (P less than 0.01). The use of serial SCC assays and cervical biopsy histology during the course of radiotherapy to predict tumor response to irradiation was assessed. In patients who were given external irradiation before intracavitary radium, a high SCC level or the presence of viable tumor cells in the biopsy was found to be of no predictive value. However, at completion of radiotherapy, i.e., after intracavitary radium application, patients with persistently high SCC levels had a significantly higher incidence of residual tumor than patients whose SCC levels returned to normal (P less than 0.01). In 60% of patients with a persistently high SCC level, viable tumor was found in the cervical biopsy at the end of radiotherapy. On the other hand, only 5.4% of patients whose SCC level returned to normal had residual tumor.     

Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay

Serum samples were collected from 611 gynecologic patients for measurement of squamous cell carcinoma antigen levels using the Abbott Laboratories squamous cell carcinoma antigen radioimmunoassay kit. Sixteen of 83 patients (19.3%) with cervical dysplasia and 72 of 135 (53.3%) with primary or recurrent cervical carcinoma had levels above 2.4 ng/mL. In contrast, only seven of 373 women (1.9%) without genital tract squamous cell intraepithelial neoplasia or carcinoma had squamous cell carcinoma antigen levels above 2.4 ng/mL. Fifty-six patients with cervical cancer were followed for correlation of squamous cell carcinoma antigen levels to disease course, and 20 had persistent or recurrent disease after therapy; rising squamous cell carcinoma antigen levels predicted disease in 15 of these 20 patients with recurrence (13 of 15 with elevated pre-treatment levels and two of five with normal pre-treatment levels). Rising squamous cell carcinoma antigen levels preceded the clinical detection of disease in ten patients by a mean of 4.6 months (range 2-7.5 months); in the remaining five, squamous cell carcinoma antigen levels were elevated only when disease recurrence was documented. Although measurement of squamous cell carcinoma antigen levels is not a sensitive screening method for cervical cancer (sensitivity 53.3%), the test has good specificity (94.3%); the majority of patients with false-positive elevations had other genital tract squamous cell neoplasias. The squamous cell carcinoma antigen assay may be a useful aid for monitoring the disease course of cervical carcinoma.     

Post-treatment serial serum squamous cell carcinoma antigen (SCC) in the monitoring of squamous cell carcinoma of the cervix

Serum squamous cell carcinoma antigen (SCC) was raised in 62% of 308 patients with squamous cell carcinoma of the cervix before treatment. Post-treatment SCC levels were raised in 69 patients (22.4%). Retrospective review showed that persistently raised SCC level after treatment was significantly associated with persistent or recurrent disease in squamous cell carcinoma of the cervix. The specificity of persistently raised SCC level in association with recurrent disease was 98.2%. The sensitivity in association with recurrent disease was 74.7%. The positive predictive values was 94.2%. The median lead time for recurrence was 4 months. SCC was raised in 38% of patients with clinical evidence of disease in the vagina. One patient had raised SCC one month prior to clinical detection of vaginal metastasis and was salvaged by an exenterative procedure. SCC was raised in 71–91% of patients with metastatic disease in the lung, lymph nodes or other distant sites. Thus, persistently raised SCC level after treatment of squamous cell carcinoma should alert the clinician to look for recurrent disease especially in distant metastatic sites. Post-treatment raised SCC level was associated with less than 5% 5-year survival rate whereas in patients with normal SCC level, the 5-year survival rate was 87%.     

Squamous cell carcinoma antigen in patients with cancer of the uterine cervix

The serum concentrations of the tumor-associated antigen SCC were determined in 62 patients with invasive carcinoma of the uterine cervix. Antigen values above 2.0 ng/ml were considered as slightly positive, and those above 4.0 ng/ml as highly positive. Pretherapeutic levels were elevated (greater than 2.0 ng/ml) in 68% of the patients with cervical carcinoma. In 49 patients with carcinoma in situ, 18% of the SCC values were above the normal range. The greatest incidence of positive SCC titers (84%) was observed in women with recurrent cervical carcinoma. Only 6.7% of women in remission had elevated titers. Five of 24 cases (21%) with invasive endometrial carcinoma had SCC values exceeding 2.0 ng/ml. Slightly positive levels of tumor antigen were seen in 1.8% (1/56) of the control subjects. Serial SCC determinations revealed a correlation with the clinical course of disease in 84%. The determination of SCC is useful for the surveillance of patients with cervical squamous cell carcinoma.     

Significance of serum SCC antigen as a tumor marker in patients with squamous cell carcinoma of the vulva

The significance of serum SCC antigen as a tumor marker was investigated in 94 women with squamous cell carcinoma of the vulva. The incidence of elevated serum SCC levels varied from 10% in FIGO stage I to 40% in FIGO stage IV. We did not observe a correlation between elevated pretreatment SCC values and the presence of lymph node metastases. During follow-up, elevated serum SCC values were observed in 8 of 19 patients (42%) with recurrent or progressive disease. It is concluded that the determination of serum SCC levels does not provide additional information in the staging of squamous cell vulvar carcinoma, but can be useful for the early detection of recurrent disease during follow-up in some patients. However, elevated serum SCC levels were also found in 25% of patients without demonstrable tumor activity during follow-up and benign skin disorders were recognized as a cause of false-positive SCC results.     

Tumor markers CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen in patients with adenocarcinoma of the uterine cervix

Between 1978-1987, 439 patients with primary cervical carcinoma were admitted to our department. Seventy-seven patients (17.5%) had cervical adenocarcinoma and are reviewed in this retrospective study. Serial serum samples of these 77 patients were analyzed for cancer antigen 125 (CA 125), squamous cell carcinoma antigen, and carcinoembryonic antigen. Before treatment, only elevated serum CA 125 levels varied directly with the clinical stage of disease. In stages IB and II disease (International Federation of Gynecology and Obstetrics [FIGO]), the incidence of elevated serum CA 125 levels was highest in patients with adenosquamous tumor. Serum marker levels, measured 3 months after therapy, concurred with the treatment results. At that time, 17 of the 23 cases (74%) with at least one elevated serum marker level either had residual disease (N = 9) or developed recurrent disease during follow-up (N = 8), compared with six of the 40 cases (15%) with normal serum marker levels (P less than .001). Increasing serum marker levels during follow-up coincided with or preceded the clinical detection of recurrent disease. Tumor relapse, clinically located in the vaginal vault, occurred concomitant with a rise of at least one serum marker level in six of the seven cases (86%). All 15 patients with abdominal recurrence showed elevation of CA 125. In progressive disease, very high serum CA 125, squamous cell carcinoma antigen, and carcinoembryonic antigen levels were determined in patients with adenosquamous tumor, whereas patients with adenocarcinoma demonstrated only high CA 125 levels. We conclude that all three markers are important for monitoring patients with cervical adenocarcinoma.     

Use of serum squamous cell carcinoma antigen assays in chemotherapy treatment of cervical cancer

Serum squamous cell carcinoma antigen levels of 15 patients with recurrent or progressive squamous cell carcinoma of the cervix on chemotherapy treatment were assayed. In 13 of these 15 patients (86.7%), clinical response was positive correlated with change in serum SCC level. A stationary or rising serum SCC level indicated that the disease is probably stationary or progressive and chemotherapy should be stopped or changed.     

Cervical carcinoma: a comparison of four potential biochemical tumor markers

A longitudinal study of circulating immune complexes (CIC), cancer antigen 125 (CA125), carcinoembryonic antigen (CEA) and a sub-fraction of the TA-4 squamous cell carcinoma tumor-associated antigen (SCC) has been undertaken in 38 patients with cervical carcinoma. Pre- and post-treatment values have been compared with those obtained in well-defined clinical remission and relapse phases of their disease. Each tumor marker was assessed in terms of "lead time" before clinically obvious recurrent disease became evident. The data from the four subjects with adenocarcinoma of the cervix gave equivocal results and no firm conclusions could be drawn. However, for the 34 patients with squamous cell carcinoma the medium value (data was skewed) for SCC was elevated above normal in the presenting pretreatment sera (4.5 ng/ml) and significantly fell to 2.5 ng/ml post-treatment (P less than 0.01). A similar pattern was not apparent for CIC, CEA, or CA125 data. When results were examined for an individual patient, of those with recurrent squamous cell lesions who died, 12/24 demonstrated elevated, and rising SCC values before clinical evidence of the disease and a further 6 (25%) at the time recurrence was clinically evident. This information gave lead times of between 2 and 52 months (median 13 months) for 75% of patients. Only 1 subject had values which remained in the normal range (less than 2 ng/ml) even though their disease was progressive. Similarly of the subjects still in clinical remission 8/9 had values within the normal range. The data for CIC, CA125, and CEA were not individually useful as a marker. Furthermore, combining the data from all analytes to give a panel of potential markers did not improve the prognosis already evident with SCC alone. It has therefore been concluded that SCC is a useful biochemical marker of the progression of squamous cell carcinoma of the cervix.     

Cancer of the uterine cervix: sensitivity and specificity of serum squamous cell carcinoma antigen determinations

Between 1978 and 1989, 451 patients with cervical squamous cell carcinoma were referred to our department, of whom 143 experienced persistent or recurrent disease. Serial serum samples of the patients were analyzed for the presence of squamous cell carcinoma antigen (SCC). The incidence of elevated pretreatment serum SCC levels ranged from 37% in stage IB (N = 173) to 90% in stage IV (N = 19). Multivariate analysis showed that deep stromal infiltration and lymph node metastases were associated with significantly higher serum SCC levels. Serum SCC trends correlated with the course of disease: after treatment the sensitivity (percentage positive results in patients with persistent disease) was 79% and the specificity (percentage negative results in patients with no evidence of disease) was 91%. During follow-up, the sensitivity of the assay was 85.5% in patients with recurrent disease. However, the positive predictive value of a single serum SCC value greater than 2.5 ng/ml for tumor recurrence was only 49%. This figure rose to 76% when two consecutive elevations were determined. Stage and pretreatment serum SCC level were the only factors found to influence survival, using Cox's regression analysis with five pretreatment variables.     

The value of squamous cell carcinoma antigen in patients with locally advanced cervical cancer undergoing neoadjuvant chemotherapy

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 (greater than 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 less than 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 less than 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.     

An evaluation of squamous cell carcinoma antigen in patients with cervical squamous cell carcinoma

In a prospective study, serum concentrations of squamous cell carcinoma antigen, a subfraction of tumor antigen (TA-4), were determined by radioimmunoassay from healthy donors, pregnant women, and subjects with various benign and malignant gynecologic diseases. Ninety-six percent of 99 healthy persons including all 52 female controls, the 15 pregnant patients, and all 23 subjects with benign gynecologic tumors, had squamous cell carcinoma antigen levels less than 2.0 ng/ml. Seven of 51 (14%) patients with cervical intraepithelial neoplasia and 16 of 24 (67%) patients with cervical squamous cell carcinoma had squamous cell carcinoma antigen levels greater than 2.0 ng/ml. Declining and rising levels of squamous cell carcinoma antigen, which were determined sequentially in nine cases of cervical carcinoma that were associated with elevated pretreatment levels of squamous cell carcinoma antigen, correlated with regression and progression of the disease. Serial serum levels of squamous cell carcinoma antigen provide a noninvasive means of monitoring the effects of individual therapy in patients with cervical squamous cell carcinoma.     

Squamous cell carcinoma antigen in cervical cancer.

Squamous cell carcinoma (SCC) antigen was described as being associated with malignant disease of the uterine cervix, and was determined by a radioimmunoassay technique. We studied squamous cell carcinoma serum levels in 72 patients from our gynecological clinic. Forty-three were diagnosed as having gynecological malignancies, and 29 as having benign diseases. The malignant disease group included 35 carcinomas of the uterine cervix, 7 endometrial cancers, and 3 vulvar cancers. Gynecological cancers were classified according to the FIGO system. We also determined SCC levels among 69 healthy subjects. Results showed that 97.1% of healthy subjects were below the cut-off point, 2.5 micrograms/l. Patients with benign gynecological diseases had increased SCC levels in 5.9% of cases. Among gynecological cancers, 56% of 23 cases of cervical cancer and one of three vulvar cancer, all of them in the active phase, had increased levels. The nine squamous carcinomas of the cervix with no evidence of disease, as well as seven endometrial adenocarcinomas with active disease were negative. Thirty-three percent of 12 cervical cancers in Stages I and II were high levels, compared to 81% of 11 advanced stages; none of the 2 early stage carcinoma of the vulva, but 1 advanced stage were increased. SCC is clinically applicable to monitor size and tumor volume of carcinomas of the uterine cervix derived from squamous epithelium.