Can treatment of carcinoma of the cervix be individualized?

Assessment of response of cervical cancers to irradiation by the conventional histological method of biopsies done during the course of radiotherapy in 51 Stage I and early stage II patients was discussed. The prediction of response to irradiation was based on the nuclear and cytoplasmic changes in the tumor cells. Two applications of intracavitary radium or external irradiation followed by intracavitary radium were given to the patients. Wertheim hysterectomy was done 4–6 weeks after irradiation in the former and 3–4 weeks after irradiation in the latter. The accuracy of the prediction was correlated with the presence of residual growth in the surgical specimens. The prediction based on biopsies done after intracavitary radium was found to be of significance. If the patient was treated initially by external irradiation, biopsy should only be taken after 5400 rad or on completion of the whole course. Validity of this study was discussed. It was concluded that it is possible to select patients who would respond poorly to irradiation for surgery.     

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 (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.     

The role of pretreatment squamous cell carcinoma antigen level in locally advanced squamous cell carcinoma of the uterine cervix treated by radiotherapy

The purpose of this study was to determine the pretreatment serum squamous cell carcinoma antigen (SCC-ag) level as a generally applicable measurement in predicting and estimating the treatment outcome of patients with locally advanced SCC of the cervix. Three hundred fifty-two patients with stage IIB-IVA SCC of the cervix were managed with both external irradiation and high-dose rate intracavitary brachytherapy. A significantly higher median SCC-ag was seen in association with increasing stage, tumor size, and lymph node involvement. The difference in disease-free survival (DFS) between stages IIB and III patients was not statistically significant with SCC-ag level <2 ng/mL. In multivariate analysis, median SCC-ag level (> or =6.0 ng/mL) and lymph node metastases had significant independent effects on absolute survival and DFS. A direct linear relationship (y=-2.932x+ 84.896) existed between the median SCC-ag of groups distributed by pretreatment prognostic factors and the 5-year DFS rate. The 5-year DFS rate as a function of SCC-ag level defined by cervix size, lymph node status, and hydronephrosis was obtained from a formula combining risk scores and the baseline survival function. From the obtained formulas, we can objectively estimate the treatment outcome in patients with locally advanced squamous cell cervical cancer.     

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.     

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.     

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.     

Endometrial carcinoma with cervical involvement (stage II): prognostic factors and value of combined radiological-surgical treatment

Tumor infiltration into the cervical mucosa, defined as infiltration into either glandular and/or squamous epithelium and the underlining stroma, could, when reevaluated, be verified in only 96 (56.3%) out of 174 cases originally recorded as Stage II endometrial cancer. The finding of “free floating tumor cells” in the cervical scraping material was associated with a lower frequency of blood/lymph vessel invasion, and these cases had a prognosis similar to Stage I disease. Poor prognostic factors were grossly invaded cervix, enlarged uterine cavity, deep myometrial infiltration, invasion into endothelial lined spaces, and poorly differentiated tumors. Clear cell carcinomas had significantly poorer prognoses than pure adenocarcinomas. The majority of the patients received preoperative radium packing. Six patients experienced major complications, all occurring in cases treated with a combination of intracavitary radium packing and external irradiation. The complication risk was clearly related to the irradiation dosage from the radium packing. In the prospective clinical trial 40 cases with Stage II adenocarcinomas receiving 4000 rad postoperative irradiation to the pelvic lymph nodes (Group B) had a similar 5-year survival rate (85%) as the 44 cases receiving no external radiotherapy (Group A). Moreover, seven pelvic recurrences were seen in Group B, and only one in Group A (P < 0.05). No subgroup of patients could be identified for which external radiotherapy improved the outcome.     

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.     

Preoperative irradiation for carcinoma of the endometrium: Indications and results

One hundred thirty patients with carcinoma of the endometrium were treated preoperatively with external irradiation (4000 rad) and radium application (2500 mg/hr or 2000 rad). Criteria for preoperative irradiation included: large uterus [19], signs of myometrial invasion on hysterogram [50], cervical involvement [37], poorly differentiated or anaplastic carcinoma [13], adenosquamous cell carcinoma [10], or squamous cell carcinoma [1]. Hysterography was performed as part of the pretreatment work-up in 93 patients (71%). Diffuse, multiple or single large defects were observed in the fundus in 72%, 8% had defects in the lower uterine segment, and the remaining 20% showed no gross defects on hysterography. Eighty-seven (67%) had no residual tumor in the hysterectomy specimen, while residual carcinoma was seen in forty-three (33%). No local recurrence has developed in the pelvis or vagina. Six patients have developed extra-pelvic metastasis, and four have died of disease. Overall survival is 97% with follow-up of 1 to 6 years.     

Assessment of cervical cancer radioresponse by serum squamous cell carcinoma antigen and magnetic resonance imaging

OBJECTIVE: To investigate the possibility of objective clinical assessment of the radioresponse of cervical cancer via determination of serum squamous cell carcinoma antigen levels and magnetic resonance imaging (MRI)-based estimation of tumor shrinkage. METHODS:The cases of 60 patients undergoing definitive radiotherapy for cervical squamous cell carcinoma (stage I-II: n = 20; stage III-IV: n = 40) were reviewed. Measurements of serum squamous cell carcinoma antigen levels (n = 60), estimated tumor volume on preradiotherapy MRIs (n = 60), and evaluated tumor shrinkage on postradiotherapy MRIs available (n = 30) were taken. The relation between postradiotherapy squamous cell carcinoma antigen level 2 months after the start of radiotherapy and disease recurrence was investigated. Regression analysis of tumor volume measured on MRIs was used to estimate the extent of tumor shrinkage 2 months after the start of radiotherapy. RESULTS: Preradiotherapy squamous cell carcinoma antigen levels correlated significantly with preradiotherapy tumor volumes. Recurrence was identified in 27 patients as distant (n = 19), distant and local (n = 1), local (n = 5), or regional (n = 2). Of 51 patients with elevated preradiotherapy squamous cell carcinoma antigen levels, 33 achieved normalized levels after radiotherapy. Squamous cell carcinoma antigen normalization was associated with a higher recurrence-free survival rate at 2 years (74.3%) than that associated with nonnormalization of squamous cell carcinoma antigen (5.6%, P <.001). The extent of shrinkage ranged from 61% to 100%, and there was no local recurrence. CONCLUSION: Postradiotherapy squamous cell carcinoma antigen status is a useful indicator of clinical outcome, particularly about tumor recurrence. It is not, however, useful for assessing response to radiotherapy. Magnetic resonance imaging is useful for obtaining an objective assessment of radioresponse.     

Results of radical surgical procedures after radiation for treatment of invasive carcinoma of the uterine cervix in a private practice

An analysis is made of the results of treatment of 96 women with carcinoma of the cervix, Stages IB and II, in a private practive. All 96 women were treated preoperatively with uterine intracavitary radium, followed 6 weeks later by Wertheim hysterectomy with pelvic lymphadenectomy. If malignant tumor was present in the lateral pelvic lymph nodes, external radiation was given postoperatively. The over-all survival rates were: Stage IB, 88% and 84% at 5 and 10 years; Stage II, 72% and 62% at 5 and 10 years. Regardles of the clinical stage, the highest survival rates were found in those patients who had no malignancy in the lateral pelvic lymph nodes and no residual cervical carcinoma. The lowest survical rates were found in those patients who had both residual cervical carcinoma and lymph node metastases.     

Hemostatic radiotherapy in carcinoma of the uterine cervix

Objective: To evaluate the treatment of hemorrhagic carcinoma of the uterine cervix with hemostatic radiotherapy (external and intracavitary radiotherapy). Method: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed. The age of the patients ranged between 30 and 60 years with a median of 42 years. Results: The mean tumor volume was 130 mm³; all cases were classified as FIGO stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out either by the external or intracavitary technique. The control of hemorrhage was 100% within 12–48 h after radiotherapy. However 85% of patients failed locally in the form of residual, recurrent pelvic or metastatic disease, within 24 months of follow-up. Conclusion:Hemorrhagic cervical cancer has a poor prognosis.     

Prognostic value of persistent cancer cells in vaginal smears of patients with cervical carcinoma treated by radiotherapy

In an attempt to improve the therapeutic scheme in cervical carcinoma a clinical research program involving 100 patients with stages 1 and 2 of cervical carcinoma was started. All patients underwent radiation treatment only. In the series 32 patients were state 1 and 68 stage 2. About 1/2 had undifferentiated squamous epithelioma and the others moderately differentiated epthelioma. Radiotherapy consisted of intracavity radium of 5000 mg-hr. and an external telecobalt irradiation up to 4000 rad tumor dose through 4 portals. During and after radiotherapy patients were followed by clinical examiniations and vaginal smears. Months after beginning of treatment another cervical punch biopsy was done. The 3 year recovery rate was 97% of stage 1 but only 75% of stage 2 patients. Recovery seemed better in well differentiated epithelioma and in cases treated first with external radiation. There were 13 deaths from recurrent disease within 5 to 35 months after begining of treatment. Punch biopsies performed 4 months after beginning of treatment revealed carcinomatous tissue in the cervical area of only 2 of these 13 patients. In all 87 survivors, abnormal cells disappeared from vaginal smears by 7 weeks. In the 13 fatal cases, abnormal cells persisted for 7 weeks or beyond. In 5 of the 13 fatal cases, tumor cells in the vaginal smears persisted throughout the remainder of the patients' lives. Other follow-up methods seemed inefficient cases. Well defined vaginal cytology seemed of most prognostic value. The radioresistent group could be submitted to complementary surgical treatment to improve the prognosis.     

Clinical significance of combined use of macrophage colony-stimulating factor and squamous cell carcinoma antigen as a selective diagnostic marker for squamous cell carcinoma arising in mature cystic teratoma of the ovary

OBJECTIVES: Mature cystic teratoma of the ovary transforms into malignant tumors, mostly squamous cell carcinomas, at an incidence of approximately 2%. Preoperative diagnosis of squamous cell carcinoma arising in mature cystic teratoma of the ovary is a difficult task. The present study aims to assess whether combined use of two serum tumor markers, macrophage colony-stimulating factor (M-CSF) and squamous cell carcinoma antigen (SCC), is effective in preoperatively diagnosing squamous cell carcinoma arising in mature cystic teratoma of the ovary, distinguishing it from mature cystic teratoma without malignant transformation. METHODS: Serum levels of M-CSF and SCC were assayed using blood samples collected preoperatively from 31 patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary and 133 patients with mature cystic teratoma of the ovary without malignant transformation. RESULTS: In 22 of the 31 (71.0%) patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary, the serum M-CSF levels exceeded the upper limit of the normal level (1056 U/ml). This positive incidence of the elevated serum M-CSF levels was significantly higher compared with that (13.5%, 18/133) observed in patients with benign cystic teratoma of the ovary (P < 0.0001). Regarding the serum levels of SCC, 13 of 31 (41.9%) patients with malignant tumors showed positive values exceeding the cutoff value of 2.0 ng/ml. Again, this incidence of positive cases was significantly higher compared with that (15.0%, 20/133) observed in patients with benign tumors (P < 0.01). There was no correlation between the serum levels of M-CSF and SCC among patients with squamous cell carcinoma arising in mature cystic teratoma of the ovary. Patients with malignant tumors testing positive for elevated M-CSF did not necessarily test positive for SCC. Patients with positive values for excess M-CSF and/or SCC constituted 87.1% of the total (27/31). Even when patients were restricted to those with stage I tumors, a value as high as 83.3% (15/18) was still obtained for those testing positive for elevated M-CSF and/or SCC. CONCLUSION: Serum M-CSF was proven to be useful as a tumor marker for detecting squamous cell carcinoma arising in mature cystic teratoma of the ovary. Combined use of serum M-CSF and SCC as a marker seemed to be useful in the selective diagnosis of mature cystic teratoma of the ovary harboring malignant squamous carcinoma, discriminating it from that without malignant carcinoma.     

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.     

Squamous cell carcinoma antigen and carcinoembryonic antigen levels as prognostic factors for the response of cervical carcinoma to chemotherapy

Between January 1986 and December 1988, 36 patients with primary advanced or recurrent cervical carcinoma were treated with cytostatic drugs in our department. Treatment at first was a combination of cisplatin and etoposide. After August 1987, a combination of carboplatin and ifosfamide was used. In all patients showing primary response to therapy, the squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) levels fell rapidly to normal after one or two cycles. In contrast, clinical remission was not obtained in those patients with levels which remained high or rose again following an initial decrease. Chemotherapy is often the only available therapy for advanced cervical carcinoma or recurrent disease, although the results of treatment, especially in squamous cell carcinoma, remain poor. The course of the SCC or CEA levels can help to decide whether the patient would profit from a continuation of the therapy. With the tumor markers, treatment can be individualized so that, above all, cases of therapy failure or further tumor progression can be detected early and the patient can be spared the severe side effects of the treatment.     

子宫颈鳞癌和腺癌的放射敏感性比较

目的比较子宫颈鳞癌和腺癌的放射敏感性。方法二次后装治疗后,比较宫颈鳞癌和腺癌肿瘤缩小和肿瘤细胞放射性损伤程度,同时用免疫组织化学ＡＢＣ法检测放射治疗前后宫颈鳞癌和腺癌的增殖细胞核抗原指数（ＰＩ）并进行比较。结果二次后装治疗后,宫颈鳞癌局部肿瘤缩小≥５０％者占７０％（２１／３０）,腺癌为２７％（４／１５）,差异有极显著性（Ｐ＜０．０１）。宫颈鳞癌放射性损伤为Ⅱｂ～Ⅲ级者占６０％（１８／３０）,腺癌为２０％（３／１５）,差异有显著性（Ｐ＜０．０５）;宫颈鳞癌放射治疗后ＰＩ从５３５０％±４３４％降至３９３０％±４０２％,差异有极显著性（Ｐ＜０．００１）,而腺癌ＰＩ自３５４７％±３８３％降至３１８０％±３０６％,差异无显著性（Ｐ＞０．０５）。结论宫颈鳞癌放射敏感性高于腺癌,放射过程中ＰＩ的降低,可能是宫颈鳞癌放射敏感性的生物学基础。     

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.     

A comparison of pretreatment serum levels of four tumor markers in patients with endometrial and cervical carcinoma

CA125 (reference value [RV] = 35 U/mL), CA50 (RV = 20 U/mL), CA72.4 (RV = 3.8 U/mL) and SCC (RV = 3.6 ng/mL) levels were retrospectively assayed in blood samples collected at diagnosis from 42 patients with endometrial carcinoma, 45 patients with cervical carcinoma and 68 patients with benign uterine pathology as controls. Among the patients with endometrial carcinoma. CA50 was the antigen with the highest sensitivity (SE) (34.4%) followed by CA125 (26.2%), CA72.4 (21.9%) and SCC (16.7%). The incidence of elevated serum CA125 and CA72.4 levels was significantly greater in advanced stages than in early ones (66.7% vs 19.4%, p = 0.032 for CA125; 66.7% vs 11.5%, p = 0.012 for CA72.4), while CA50 positivity was not significantly correlated with the extent of disease (50% in advanced stages vs 30.8% in early ones, p = 0.38). Among the patients with cervical carcinoma, CA125 and CA50 respectively showed a SE of 33.3% and of 42.9% for adenocarcinoma, while SCC had a SE of 33.3% and of 42.9% for squamous cell adenocarcinoma; in particular among the patients with squamous cell carcinoma, the incidence of elevated SCC levels was correlated with the extent of tumor (57.1% in advanced stages vs 12.5% in early ones, p = 0.013). In conclusion, CA50 and CA125 were the most sensitive tumor markers in both endometrial carcinoma and cervical adenocarcinoma, while SCC was the most reliable antigen for squamous cell carcinoma of the cervix. Because of the affinity of SCC, CA50 and CA125 for different histological types of cervical carcinoma, the combined evaluation of SCC with CA50 or CA125 showed an increased SE with respect to each marker alone.