Prognostic Significance of Pretreatment Squamous Cell Carcinoma Antigen and Carcinoembryonic Antigen in Squamous Cell Carcinoma of the Uterine Cervix

Sixty-seven patients with squamous cell carcinoma of the uterine cervix (FIGO Stages IB2, IIA, and IIB) were reviewed to evaluate the pretreatment level of squamous cell carcinoma antigen (SCC) and carcinoembryonic antigen (CEA) which may be used to predict a subset of patients with poor prognosis. The rate of pathologic pretreatment serum level of SCC increased significantly in cases with Stage IIB compared to that of Stages IB2 and IIA (50% versus 16.3%). The rate of pathologic pretreatment serum level of CEA did not show any difference between these two groups (29.2% versus 30.2%). The 48-month disease-free survival for patients with pathologic pretreatment serum levels for one or both tumor-associated antigens (TAAs) was 40.0% versus 91.7% for patients with normal levels (log-rank test,P< 0.005) in Stages IB2 and IIA. Patients who had a pathologic pretreatment serum level for one or both TAAs showed higher incidence of lymph node metastasis than patients with normal levels (36.7% versus 10.8%). The patients who had pathologic pretreatment serum levels for both TAAs and lymph node metastasis have the poorest prognosis. The pretreatment serum levels for one or both TAAs make it possible to predict the clinical response to neoadjuvant chemotherapy consisting ofcis-platinum (DDP) and 5-fluorouracil (5-FU). Our findings suggest that pretreatment of SCC in conjunction with CEA is a valuable tumor marker to predict the prognosis of squamous cell carcinoma of the uterine cervix and to foresee a clinical response to subsequent neoadjuvant chemotherapy.     

Both TPA and SCC-Ag levels are prognostic even in high-risk stage Ib-IIa cervical carcinoma as determined by a stratification analysis

OBJECTIVE: To determine the prognostic values of tissue polypeptide antigen (TPA), squamous cell carcinoma antigen (SCC-Ag), and carcinoembryonic antigen (CEA) in the sera of cervical carcinoma patients, especially in those with a poor prognosis. METHODS: In this retrospective study, the preoperative serum SCC-Ag, TPA, and CEA were analyzed in 779 patients with cervical squamous cell carcinoma of stage Ib-IIa who received radical hysterectomy and pelvic lymph node dissection (RAH-PLND) between 1984 and 1994. RESULTS: Due to poor predictive value and poor correlation between serum CEA and clinico-pathological factors, CEA was abandoned in this study. Elevated TPA and SCC-Ag levels, pelvic lymph node metastasis (PLNM), lymphvascular space involvement (LVSI) and deep stromal invasion (DSI) were associated with poor survival time by univariate analysis. The correlation study showed that elevated serum TPA was significantly related to PLNM, LVSI, and DSI (p = 0.004, 0.008, and 0.021, respectively), and SCC-Ag was related to PLNM and bulky tumor size (p = 0.001 and 0.02, respectively). In the multivariate analysis, only PLNM and LVSI remained independently significant indicating poor survival. Further stratification studies by PLNM and LVSI showed that elevated TPA levels could even indicate higher recurrence rates in patients with PLNM (p = 0.045), as well as SCC-Ag in patients with LVSI (p = 0.038). CONCLUSIONS: The results suggest that both elevated TPA and SCC-Ag levels depicting poor prognosis in stage Ib-IIa cervical SCC, especially indicates a group of high-risk patients who may need more aggressive therapy.     

A comparison of prognoses of FIGO stage IB adenocarcinoma and squamous cell carcinoma

OBJECTIVES: The objective of this study was to compare clinical and pathologic variables and prognosis of FIGO stage IB adenocarcinoma and squamous cell carcinoma of uterine cervix. METHODS: A retrospective review was performed of 521 patients with stage IB squamous cell carcinoma and adenocarcinoma of cervix who treated primarily by type 3 hysterectomy and pelvic and/or para-aortic lymphadenectomy at Hacettepe University Hospitals between 1980 and 1997. RESULTS: Age, tumor size, grade, depth of invasion, lymph node metastasis, parametrial, vaginal, and lymphvascular space involvement (LVSI) were not different between two cell types except number of the lymph nodes involved. Metastasis to three or more lymph nodes was significantly higher in adenocarcinoma. Overall and disease-free survival were 87.7%, 84.0% versus 86.4%, 83.1% for squamous cell carcinoma and adenocarcinoma, respectively (P > 0.05). The rate and site of recurrence were not different between two cell types. Multivariate analysis of disease-free and overall survival revealed independent prognostic factors as tumor size, LVSI, number of involved lymph node, and vaginal involvement. CONCLUSION: Prognosis of FIGO stage IB cervical cancer patients who were treated by primarily radical surgery was found to be same for those with adenocarcinoma and squamous cell carcinoma.     

Identifying local tumor variables for operable node-negative, margin-free patients with bulky cervical carcinoma of FIGO stage IB, IIA and IIB without adjuvant therapies

PURPOSE: To identify local risk factors for FIGO IB, IIA and IIB bulky cervical squamous cell carcinoma (tumor size > or = 4 cm) patients with node-negative, margin-free tumors treated by radical hysterectomy, pelvic lymph node and para-aortic lymph node dissections without adjuvant therapies. MATERIALS AND METHODS: Thirty-four patients were recruited between 1976 and 1989 because they all declined any postoperative adjuvant therapy. The pathology reports showed that all the specimen margins were free from cancer cells with no para-aortic or pelvic lymph node metastases. The survival interval was calculated starting from the time of surgical intervention to the time of death or the end of this study in the year 2000. RESULT: Tumor variables including cell differentiation, depth of stromal invasion, parametrial invasion, vaginal invasion, uterine body invasion, age, and FIGO stage were analyzed. Only vaginal invasion showed statistical significance for decreasing patient disease-free survival in both univariate and multivariate analyses with p values of 0.003 and 0.002, respectively. CONCLUSION: For node-negative and margin-free patients with bulky cervical squamous cell carcinoma with operable stage IB and IIB, surgical intervention alone could suffice when no vaginal invasion is noted plus an 85% survival rate could be achieved. A prospective pilot study should be initiated although this study showed an excellent survival rate which is perhaps due to the limited number of cases.     

Prognostic value of p53 expression in stage IB1 cervical carcinoma

The purpose of this retrospective study was to evaluate the patterns of p53 expression in stage IB1 squamous cell carcinoma of the uterine cervix, to compare p53 expression with clinicopathological findings, and to assess its prognostic value. 27 patients with stage IB1 squamous cell carcinoma of the uterine cervix underwent abdominal radical hysterectomy and pelvic lymph node dissection. Expression of p53 was studied immunohistochemically. Overexpression of p53 was detected in 33.3% of the tumors, low expression was seen in 11.1%, and negative expression was found in 55.6%. Deep cervical stromal invasion (> or = 1/2) was found to be associated with the increased risk of lymph node metastases (odds ratio = 17.5). A significantly lower percentage of patients survived when p53 overexpression was observed (p = 0.0315). Univariate analysis revealed that tumor size (2-3.9 cm), lymph node metastasis, tumor invasion into parametria, tumor invasion into blood/lymph vessels, squamous cell carcinoma antigen (> or = 2 ng/ml), and p53 overexpression had a significantly lower recurrence-free survival rate. None of these above factors obtained significance in the multivariate analysis. This study suggests that expression of p53 may be indicative of an unfavorable prognosis in patients with stage IB1 squamous cell carcinoma of the uterine cervix.     

High-risk group in node-positive patients with stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy and postoperative pelvic irradiation

OBJECTIVE: The goal of this study was to identify risk factors in patients with node-positive stage IB, IIA, and IIB cervical carcinoma after radical hysterectomy with pelvic lymph node dissection and postoperative irradiation. METHODS: Two hundred forty-two patients with FIGO stage IB, IIA, and IIB cervical carcinoma underwent radical hysterectomy with pelvic lymph node dissection; pathological analysis of the surgical specimen showed positive lymph nodes in 59 patients. These 59 patients were further treated with postoperative radiotherapy. Eighteen patients were in stage IB, 4 in stage IIA, and 37 in stage IIB. Histological tumor type, tumor size, lymph-vascular space invasion, parametrium infiltration, number of positive nodes, and involvement of common iliac nodes were assessed for correlation with cancer recurrence. RESULTS: When all these variables were assessed in the Cox proportional regression analysis, parametrium infiltration (P = 0. 0199) and number of positive nodes (two or more nodes) (P = 0.0483) revealed the factor correlating significantly with disease-specific survival. Based on these two factors, node-positive patients could be divided into low-risk (n = 11), intermediate-risk (n = 29), and high-risk (n = 19) groups. The 5-year disease-specific survival for the low-risk group was 100% which was significantly better than the 39.1% for the high-risk group (P = 0.0012). CONCLUSION: For patients in the high-risk group, it may be worthwhile to consider new strategies to improve survival.     

Can initial serum cyfra 21-1, SCC antigen, and TPA levels in squamous cell cervical cancer predict lymph node metastases or prognosis?

OBJECTIVE: The aim of this study was to determine whether lymph node metastases or prognosis can be predicted by initial serum Cyfra 21-1, tissue polypeptide antigen (TPA), and squamous cell carcinoma antigen (SCC-Ag) levels in squamous cell cervical cancer. METHODS: Pretreatment serum levels of 92 patients were correlated with clinicopathologic parameters and prognostic data. The clinical performance of the tests was evaluated by their receiver operating characteristic curves. The prognostic power of the variables was assessed using Cox regression analysis. RESULTS: Serum levels of each marker were significantly related to tumor stage, size, and depth of infiltration. The clinical performance of each marker in predicting lymph node metastases or parametrial involvement was poor. In the stepwise Cox regression analysis, regarding patients with early stage cervical cancer (stage Ib/IIa, n = 63), tumor size (P = 0.0005) was the only independent prognostic factor for disease-free interval. Lymph node status (P = 0.0014), tumor size (P = 0.004), and parametrial involvement (P = 0.025) were independent risk factors for survival. Considering all patients with stages Ia through IVb disease, tumor size (P = 0.0001) and TPA level (P = 0. 026) were independent risk factors for disease-free interval, whereas tumor size (P = 0.0001) and parametrial involvement (P = 0. 0002) were risk factors for survival. CONCLUSIONS: Pretreatment Cyfra 21-1, TPA, and SCC-Ag levels were strongly related to tumor burden, but insufficiently reliable for identifying patients at risk of the presence of lymph node metastases or parametrial involvement. Serum levels of each marker showed no independent prognostic value in early stage cervical cancer.     

The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy

The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC-Ag of CEA in all patients had limited additional effect in predicting the prognostic significance.     

Identification of High-Risk Groups among Node-Positive Patients with Stage IB and IIA Cervical Carcinoma

The purpose of the present study was to identify a subset of high-risk patients among surgically treated node-positive patients with stage IB and IIA cervical carcinoma. From 1982 through 1991, 334 patients underwent radical hysterectomy for FIGO stage IB and IIA cervical carcinoma. In 68 patients pathological analysis of the surgical specimen revealed positive pelvic nodes. In this group, a Cox proportional hazard analysis was performed to examine the prognostic significance of clinicopathological variables. Only for adenocarcinoma (P= 0.002) and parametrium infiltration (P= 0.003) was evidence of an association with prognosis found. Based on these two factors, patients with positive pelvic nodes were categorized into a low-risk group (squamous cell carcinoma without parametrium infiltration,N= 33) and a high-risk group (squamous cell carcinoma with parametrium infiltration or adenocarcinoma,N= 34). The 5-year disease-specific survival in the low-risk group was 94% compared with 60% in the high-risk group (P= 0.003). For patients in the high-risk group, there is an urgent need for alternative adjuvant treatment to improve outcome.     

Combination of squamous cell carcinoma-antigen, carcinoembryonic antigen, and carbohydrate antigen 19-9 predicts positive pelvic lymph nodes and parametrial involvement in early stage squamous cell carcinoma of the uterine cervix

Aim: We examined the correlations between the pretreatment values of four tumor markers (squamous cell carcinoma [SCC]-antigen, carcinoembryonic antigen [CEA], carbohydrate antigen [CA]19-9, and CA125) and postsurgical high-risk factors (parametrial involvement and positive pelvic lymph nodes) in women with SCC of the uterine cervix who had International Federation of Gynecology and Obstetrics clinical stage IB and IIA disease and underwent radical hysterectomy. Material and Methods: In this retrospective study, we reviewed 291 patients between April 1989 and December 2008. The first 200 subjects, studied between 1989 and 2001, served as the training set, and another 91 subjects, studied between 2002 and 2008, comprised the test set. To evaluate the correlations between pretreatment tumor markers and postsurgical high-risk factors, the χ(2) -test and logistic regression analysis were used for univariate and multivariate analysis, respectively. Results: Multivariate analysis with receiver-operator curves showed that the combination of SCC-antigen, CEA, and CA19-9 strongly predicted postsurgical high-risk factors. Analysis of the training set showed that 66.7% (95% confidence interval, 52.6-84.8%) of patients who tested positive for at least two of these three tumor markers had postsurgical high-risk factors. Similar results were obtained with the test set. Conclusions: Preoperative levels of SCC-antigen, CEA, and CA19-9 are useful for predicting the status of postsurgical high-risk factors in women with SCC of the uterine cervix who undergo radical hysterectomy.     

Clinical significance of tumor size in stage IB and II carcinoma of the uterine cervix

Abstract. Kawagoe T, Kashimura M, Matsuura Y, Sugihara K, Toki N, Aoki T. Clinical significance of tumor size in stage IB and II carcinoma of the uterine cervix.
The purpose of the present study was to investigate the correlation between tumor size and prognosis in stage IB and II cervical cancer and to elucidate the adequacy of new FIGO staging system for cervical cancer. The subjects included 128 patients with cervical cancer (stage IB = 86, IIA = 18, and IIB = 24) who had undergone radical hysterectomy. The largest tumor size of the pathology specimen was measured in two dimensions, and the correlation between tumor size and prognosis was investigated. In addition, tumor size of the pathology specimen was compared with the largest tumor diameter measured by MRI in stage IB cancers. Patients with a tumor size greater than 3 cm² had a significantly worse 5-year survival rate (63%) when compared to those with tumor size no greater than 3 cm² (96%) ( P < 0.0001). Multivariate analysis revealed that independent prognostic factors were tumor size ( P = 0.003) and lymph node metastasis ( P = 0.015). By regression analysis, the largest tumor size of the pathology specimen was relatively well correlated with the largest tumor diameter by MRI in stage IB cancers; 3 cm² of tumor size in the pathology specimen corresponded to 3.4 cm of tumor diameter by MRI. The adequacy of new FIGO staging system was considered relatively acceptable.     

Missing association between telomerase activity and clinicopathological features in patients with early stage carcinoma of the cervix

OBJECTIVES: This study was undertaken to evaluate the association between the telomerase activity in the tumor and clinicopathological findings in patients with stage IB-IIA (FIGO) carcinoma of the cervix. METHODS: Thirty-eight patients with carcinoma of the cervix submitted to radical hysterectomy were prospectively from January 1998 to November 2001. Samples from the tumor were taken and analyzed by the telomerase PCR-TRAP-ELISA kit. Clinicopathological characteristics such as age, stage, tumor size, grade of differentiation, lymphatic vascular space invasion (LVSI), parametrial involvement and status of pelvic lymph nodes were also recorded. RESULTS: Patient's mean age was 49.3+/-1.99 years (29-76 years). The clinical stage (FIGO) was IB in 35 patients (92.1%) and IIA in 3 patients (7.9%). The histological classification identified squamous cell carcinoma in 33 patients (86.8%) and adenocarcinoma in 5 patients (13.2%). There was no association between age, clinical stage, histological classification, tumor size, grade of differentiation and presence of LVSI with tumoral telomerase activity. The telomerase activity was not associated with the presence of vaginal involvement (P=0.349), parametrium involvement (P=0.916), pelvic lymph node metastasis (P=0.988) or tumoral recurrence (P=0.328) in patients with carcinoma of the cervix. CONCLUSIONS: Telomerase activity in the tumor is not associated with clinicopathological findings or tumor recurrence in patients with early stage cervical carcinoma.     

Carcinoma of the cervix in young females (35 years, and younger)

This retrospective study involved 55 patients, 35 years old or less with invasive carcinoma of the cervix. There were 49 squamous carcinomas, 3 adenocarcinomas, and 3 unusual varieties. Thirty-five patients had stage IB disease; 4 had stage IIA disease; 6 had stage IIB disease; 5 had stage IIIB disease, and 3 had stage IV disease. Treatments employed were either radical hysterectomy and node dissection, irradiation, or irradiation followed by radical surgery. Our overall 5-year disease-free survival among young females with stage IB disease was observed to be only 43%; stage IIA only 25%; stage IIB only 17%, and no survivors in more advanced stages.     

DNA ploidy level as prognostic factor in low stage carcinoma of the uterine cervix

Flow cytometry was used to measure DNA content of tumor cells in paraffin-embedded archival material from 89 patients with squamous cell carcinoma of the cervix uteri stages IB and IIA. Patients were all treated with radical hysterectomy and transperitoneal lymphadenectomy. Twenty-four percent received radiotherapy postoperatively because of tumor spread into parametria or positive lymph nodes. Ploidy grade was compared to other prognostic factors. DNA-aneuploidy was seen in 44 (49%), DNA-diploidy in 16 (18%) and 29 (33%) of the tumors were DNA-periploid. Sixty-nine (78%) patients were in FIGO stage IB, 20 (22%) in IIA. In 19 (21%) lymph node metastases were found, vasoinvasion in 25 (28%). Overall disease-specific 5-year survival was 80%. There was a significant effect of positive lymph nodes (90% vs 47%) and vasoinvasion (87% vs 64%) on the 5-year survival (resp. P less than 0.01 and P = 0.02). No correlation was found between stage (81% for IB vs 80% for IIA) or DNA-ploidy grade (81% for aneuploidy, 82% for periploidy, 79% for diploidy) and survival (resp. P = 0.9 and P = 0.8). Ploidy grade was equally divided over other prognostic factors. In stepwise Cox regression analysis DNA-ploidy grade showed no independent effect on survival. We conclude that DNA flow cytometry in this material was of no additional prognostic value.     

Prognostic value of pre-treatment circulating monocyte count in patients with cervical cancer: comparison with SCC-Ag level

Objective

Higher level of circulating monocyte has been reported to be related with higher cancer incidence and mortality. We investigated the role of pre-treatment circulating monocyte count for cancer specific survival in cervical squamous cell carcinoma patients comparing with pre-treatment squamous cell carcinoma-related antigen (SCC-Ag) level.

Methods

We retrospectively enrolled patients with squamous cell carcinoma of the cervix (FIGO stage IB to IVA) who had complete blood cell counts with differential cell count and serum SCC-Ag level within 2 weeks before starting initial treatment and were treated at Samsung Medical Center, Seoul, Korea, from 1996 to 2007.

Results

The 788 patients in our study group had a median follow-up of 53.4 months and a five-year survival rate of 87.8%. The median value for pre-treatment circulating monocyte count was 349/μl (21-1463), and the median concentration of SCC-Ag was 1.6 ng/ml (0.1-362.0). In multivariable analysis, the pre-treatment circulating monocyte count was an independent prognostic factor for progression-free survival and overall survival in locally advanced disease (P = 0.007 and P = 0.038) but not in case of SCC-Ag for overall survival. The combined index of monocyte count and SCC-Ag level could enhance the prognostic value of SCC-Ag alone in patients with locally advanced cervical squamous cell carcinoma.

Conclusions

A higher pre-treatment circulating monocyte count is independently associated with poor prognosis in patients with locally advanced cervical squamous cell carcinoma. The pre-treatment circulating monocyte count may be considered as an adjunctive biomarker with SCC-Ag.     

Prognostic significance of histopathological classification in patients with carcinoma of the uterine cervix

In a retrospective study of 724 patients with histologically proven carcinoma of the uterine cervix from 1980 through 1986, the histological classification and clinical stage (FIGO) were investigated for their prognostic value. The clinical stage was very important in relation to prognosis. The histological type of the squamous cell carcinoma (keratinizing, large cell non-keratinizing, small cell non-keratinizing) did not have any value in predicting survival, but small cell non-keratinizing tumor showed a less favorable prognosis than other tumors when surgery was employed. As to survival, there was no difference between adenocarcinoma and squamous cell carcinoma when compared in all patients, but adenocarcinoma had a worse prognosis than squamous cell carcinoma when surgery was employed. The pelvic lymphnode status at operation was correlated with the clinical stage. Adenocarcinoma had more positive nodes than squamous cell carcinoma. There was no significant difference in the frequency of pelvic node involvement among cell types of squamous cell carcinoma. The present histopathological classification of the uterine cervical carcinoma was of little prognostic value in predicting patient outcome.     

Postoperative radiotherapy in stage IB squamous cell cervical cancer

OBJECTIVE: The purpose of the study was to evaluate postoperative whole pelvic radiation for high-risk patients with FIGO Stage IB cervical cancer. METHODS: One hundred and forty-eight patients with Stage IB squamous cell carcinoma of the cervix underwent radical hysterectomy and pelvic lymphadenectomy. The low-risk group included patients without unfavorable prognostic factors who were treated only by surgery. The high-risk group included women with pelvic node metastases, with positive or close surgical margins, clinical tumor size > 4.0 cm, depth of stromal invasion > 1/3 the cervical wall, grade 3 tumor and presence of lymphovascular space involvement. High-risk patients received whole pelvic radiotherapy between two and four weeks after surgery. RESULTS: Seventy patients (47.3%) were low risk and 78 patients (52.7%) were high risk. Locoregional recurrences were diagnosed in nine cases (12.8%) in the surgery group and in 11 patients (14.1%) assigned to radiotherapy. The incidence of distant metastases was 2.8% in the surgery group and 6.4% in the surgery and radiotherapy group. Overall survival at five years was 88.6% in the low-risk group and 84.7% in the high-risk group. CONCLUSION: Five-year overall survival, locoregional and distant metastases were similar in the low-risk and high-risk groups of patients, thus emphasizing the value of whole pelvic radiation in patients with unfavorable prognostic factors in Stage IB cervical cancer.     

P63 and EGFR as prognostic predictors in stage IIB radiation-treated cervical squamous cell carcinoma

OBJECTIVES: The purpose of this study was to determine the relation between p63, p53-related gene, epidermal growth factor receptor (EGFR), and spontaneous apoptosis in relation to radiotherapy in patients with FIGO stage IIB cervical carcinoma, who had undergone radiation and concurrent chemotherapy, retrospectively. METHODS: Eighty-four patients with FIGO stage IIB squamous cell carcinoma (SCC) of the uterine cervix, who were treated with radiotherapy and concurrent chemotherapy between 1991 and 1996, were included in the present study. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the expressions of p63 and EGFR, which were determined by immunohistochemistry and with apoptosis by TUNEL on tissue-arrayed slides. Univariate and multivariate analyses were performed to determine the prognostic factors that influence patient survival. RESULTS: Overall the indices of the expressions of p63 and EGFR in stage IIB cervical carcinoma were 18.7 and 26.6%, respectively, and these were found to be correlated. EGFR expression was significantly associated with extrapelvic failure (P = 0.03), whereas p63 was associated with locoregional failure (P = 0.03). The spontaneous apoptotic index showed no prognostic value, but the immunoreactivities of p63 and EGFR were associated with a worse prognosis by both univariate (P = 0.01 and 0.04, respectively) and multivariate analysis (95% CI:2.0-4.4, RR:3.2 and 95% CI:4.9-8.7, RR:6.7, respectively). CONCLUSIONS: The expression of p63 gene is associated with poor survival and locoregional failure, whereas EGFR expression was found to be a prognostic predictor of extrapelvic failure. Both molecules were found to be potent molecular risk factors in patients with FIGO stage IIB SCC of the uterine cervix, who had received radiotherapy and concurrent chemotherapy.     

Identification of prognostic factors and risk groups in patients found to have nodal metastasis at the time of radical hysterectomy for early-stage squamous carcinoma of the cervix

In a retrospective study conducted at the University of Alabama at Birmingham, the University of Michigan, and the Mayo Clinic, 185 patients with previously untreated FIGO stage IB and IIA squamous cell carcinoma of the cervix were found to have nodal metastasis at the time of radical hysterectomy and pelvic lymphadenectomy. Of these patients, 103 received adjuvant pelvic irradiation. Cancer recurred in 76 patients; the median time to recurrence was 3.1 years. The prognostic significance of patient age, clinical stage, lesion diameter, number and location of nodal metastases, and use of adjuvant radiation therapy was determined by multivariate analysis. Only patient age (P = 0.0006), lesion diameter (P less than 0.0001), and number of nodal metastases (P = 0.0004) were noted to be significant factors in determining overall survival. Rates of recurrence were also related to these factors. Employment of these significant variables led to identification of four risk groups. In general, patients with small cervical lesions (diameter less than 1 cm) and no more than two nodes with metastases fell into the low-risk category; those patients with large cervical lesions (diameter greater than 4 cm) and more than two involved nodes fell into the high-risk category. All other patients were categorized into intermediate-risk groups. Ten-year survival was 92% in the low-risk group (n = 13), 70% in the low-intermediate-risk group (n = 66), 56% in the high-intermediate-risk group (n = 66), and 13% in the high-risk group (n = 20). This risk group classification identifies subgroups of early-stage cervical carcinoma patients found to have nodal metastasis at the time of radical hysterectomy that warrant appropriately selected adjuvant therapy.     

Concurrent chemoradiotherapy followed by adjuvant chemotherapy in uterine cervical cancer patients with high-risk factors

OBJECTIVES: To determine whether concurrent chemoradiotherapy (CCRT) followed by adjuvant chemotherapy is better than CCRT alone in the management of FIGO stage bulky IB and IIB uterine cervical cancer. METHODS: Two hundred and five FIGO stage bulky IB and IIB patients with squamous cell carcinoma of the uterine cervix treated with CCRT were divided into 2 groups: (1) CCRT alone (n=103, Group A) and (2) CCRT plus adjuvant chemotherapy (n=102, Group B), and treatment outcomes were retrospectively compared between the two patient groups. RESULTS: Only 63% of patients received all three planned cycles of adjuvant chemotherapy, while 16% received only one cycle because of increased treatment-related morbidity or other causes. There were no treatment-related deaths. Although 37 patients experienced failures after completion of treatment, no significant differences were found in patterns of local and regional failures between the two groups. The incidence of distant metastasis, including para-aortic or supraclavicular lymph node metastases, was not reduced in patients of Group B (8% in Group A vs. 7% in Group B). Overall five-year actuarial survival rates for Group A and Group B patients were 85% vs. 80%, and five-year disease-free survival rates were 83% vs. 78%, respectively. CONCLUSIONS: Our data failed to show discernable therapeutic advantage of adjuvant chemotherapy with given after CCRT for the management of FIGO stage bulky IB and IIB uterine cervical cancer patients. A future clinical trial will be necessary to test the clinical efficacy of the adjuvant treatment using newly developed agents in uterine cervical cancer patients.