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.     

The role of chemotherapy in squamous cell carcinoma of the uterine cervix: a review

A critical review of the potential role of chemotherapy in the management of patients with squamous cell carcinoma of the uterine cervix is presented. Both its role in the management of recurrent and/or metastatic cervical cancer and its usefulness as part of the primary treatment of high-risk patients are discussed. It is emphasized that high-risk patients with cervical cancer should preferably be treated in specialized centers and entered into research protocols.     

宫颈鳞癌微血管密度血管内皮生长因子表达意义的研究

目的探讨宫颈鳞癌微血管密度、血管内皮生长因子(VEGF)蛋白表达在判断肿瘤生物学行为中的意义,以期为宫颈癌的预后评估和指导临床治疗提供新的依据.方法应用免疫组织化学SP法检测宫颈癌组织中微血管密度、VEGF蛋白表达,分析其与肿瘤组织学分级、临床分期及它们相互之间的关系,并分别研究其与预后的关系.结果宫颈鳞癌微血管密度、VEGF蛋白表达与肿瘤组织学分级、临床分期无关;VEGF阳性组微血管密度明显高于阴性组(P＜0.01).微血管密度较高组的存活率低于微血管密度较低组(P＜0.01),VEGF表达对存活率无明显影响(P＞0.05).结论宫颈鳞癌VEGF阳性组微血管密度高于阴性组,说明VEGF有促进宫颈鳞癌血管形成的作用.癌组织中微血管密度与预后有关,提示肿瘤微血管化的评估可能会成为一种新的预测宫颈鳞癌预后的手段.     

A comparison of ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix

OBJECTIVE: The purpose of our study was to investigate a possible difference in ovarian metastasis between squamous cell carcinoma and adenocarcinoma of the uterine cervix and to confirm clinicopathological variables associated with the metastases. METHODS: Clinical and pathological variables of 1064 patients with invasive squamous cell carcinoma and 240 with adenocarcinoma were studied. RESULTS: Ovarian metastasis was found in 14 patients (1.3%) with squamous cell carcinoma and 15 (6.3%) with adenocarcinoma. The mean age of patients with ovarian metastasis of squamous cell carcinoma was 57.4 years, compared to 50.2 years for adenocarcinoma. Ovarian metastasis of adenocarcinoma was more likely to be visible (40.0%) and present in both ovaries (66.7%), while these two characteristics occurred in only 21.4 and 36.7% of patients with squamous cell carcinoma. A logistic regression analysis with clinical variables indicated that clinical stage beyond IIb was a significant variable of squamous cell carcinoma, and more than 30-mm tumor size was significant in adenocarcinoma. CONCLUSION: The incidence of ovarian metastasis of adenocarcinoma of the uterine cervix was significantly higher than that of squamous cell carcinoma. The incidence of adenocarcinoma was associated more closely with tumor size than clinical stage, whereas it was more associated with clinical stage in squamous cell carcinoma. The results thus suggested that the differences in ovarian metastases were caused by the different characteristics of the two types of carcinoma.     

Prognostic significance of epithelial-stromal vascular cuffing and microvessel density in squamous cell carcinoma of the uterine cervix.

OBJECTIVE: Tumor angiogenesis has been shown to play an important role in tumor growth and metastasis. This study examines the prognostic significance of two histological markers of angiogenesis, i.e., vascular cuffing (VC), a bead-like arrangement of microvessels closely surrounding microscopic tumor nests, and microvessel density (MVD), the number of microvessels in a unit area, in cervical squamous cell carcinoma. METHODS: One hundred twenty-two specimens from surgically resected uteri with cervical squamous cell carcinoma were histologically reviewed and immunostained for CD34. VC was graded into "none," "incomplete," and "complete." The MVD was determined by counting the microvessels with a light microscope within a x200 field area where neovascularization occurred most actively. Stromal inflammation was also split into three grades. The relationship of VC or MVD to clinicopathological prognostic factors such as FIGO stage, cervical stromal invasion, lymph-vascular space invasion, pelvic lymph node metastasis, and parametrial invasion was evaluated using univariate and multivariate analyses. RESULTS: The patients with a complete VC pattern showed a significantly worse prognosis compared to those with a pattern graded as either none or incomplete (P<0.011 and P<0.0001, respectively). The Cox regression analysis revealed the complete VC pattern, together with parametrial invasion, to be an independent prognostic indicator for overall survival. MVD and the grading of stromal inflammation showed no significant relationship with VC or overall survival. CONCLUSIONS: The complete VC pattern may therefore be a useful prognostic indicator in cervical squamous cell carcinoma.     

Angiogenesis in cervical intraepithelial neoplasia and early-staged uterine cervical squamous cell carcinoma: clinical significance

The objective of this study is to evaluate angiogenesis in cervical intraepithelial neoplasia (CIN), microinvasive squamous cell carcinoma (MIC), and early-staged squamous cell carcinoma (SCC), stage IB-IIA of the cervix. Microvessel density (MVD) was evaluated and correlated with other pathologic prognostic factors and disease outcomes. Four hundred seventy-four cervical specimens were studied. Among these, 100 were designated normal cervix, 30 CIN1, 32 CIN2, 178 CIN3, 74 MIC, and 60 early-staged SCC. MVD per high-power field (x400) of early-staged SCC, MIC, and CIN3 were significantly higher in comparison to CIN2, CIN1, and control subjects (P<0.05). There was no statistically significant difference in MVD between control group, CIN1, and CIN2. In early-staged SCC, no correlation between MVD and pelvic lymph node status, parametrial involvement, depth of stromal invasion, and lymphovascular space invasion was found. Patients with bad outcomes (recurrence or death) showed no statistically different MVD from the ones who had unremarkable clinical courses.     

Long-term outcome and prognostic factors in patients with cervical carcinoma: a retrospective study

This study evaluates treatment outcomes and possible prognostic factors of inoperable cervical cancer patients treated with external beam radiotherapy (EBRT) and high-dose rate brachytherapy (HDR BRT). Between 1993 and 2000, 183 patients with cervical cancer were treated at our institute. Radiotherapy was the sole treatment modality until January 1997; after the announcement of National Cancer Institute in 1999, 40 mg/m(2) of cisplatin (49%) was routinely applied every week. Median age was 54 years (32-92 years). Most patients (88%) had advanced-stage disease (IIB-IIIB). With a median follow-up time of 45 months (6-121 months), the 5-year overall survival (OS), local recurrence-free survival, disease-free survival (DFS), and distant metastasis-free survival (DMFS) rates were 55%, 71%, 51%, and 77%, respectively. Univariate analysis revealed that age, tumor size, lymph node status, and concomitant cisplatin were prognostic factors for OS. The DFS rates were lower in young age group. Patients with tumor greater than 4 cm and age greater than 40 were at greater risk for local recurrence. Distant metastases were more frequent in patients with adenocarcinoma. Concurrent cisplatin use increases DMFS rates (91% vs 78%; P= 0.05). In multivariate analysis, extensive stage, parametrial infiltration, young age, adenocarcinoma histopathology, and lymph node metastasis were negative prognostic factors for OS while concomitant cisplatin increases OS. Likewise, patients with extensive stage, adenocarcinoma, and without concurrent cisplatin administration had more risk for distant metastasis. There was no treatment-related mortality. Grade 3-4 morbidity rates were seen only in eight patients (4%). The combination of EBRT and HDR BRT together with concomitant chemotherapy in the treatment of locally advanced carcinoma of cervix is safe and well tolerated with acceptable morbidity.     

Scalp metastasis from squamous cell carcinoma of the cervix

Abstract. Maheshwari GK, Baboo HA, Ashwathkumar R, Dave KS, Wadhwa MK. Scalp metastasis from squamous cell carcinoma of the cervix.
We describe a 45-year-old woman with squamous cell carcinoma of the cervix stage IIB, who was initially treated with radical radiotherapy. The patient developed multiple scalp metastases 8 months following her treatment. The scalp was involved in the disease as the sole anatomic site of distant cutaneous metastasis. The scalp lesions were treated with palliative radiotherapy. A search of the literature revealed only two cases of such distant metastatic involvement of the scalp from cervical cancer.     

Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors

To evaluate the efficacy of postoperative radiotherapy and to investigate prognostic factors for early-stage cervical cancer patients. From December 1993 to December 2001, 141 patients with stage I-II cervical cancer without para-aortic lymph node (LN) metastases and treated by surgery and postoperative radiotherapy (RT) were included in this study. Indications for postoperative external RT were based on pathologic findings, including LN metastasis, positive surgical margins, parametrial involvement, pT2 tumor, and presence of any two minor risk factors like lymphvascular space involvement, deep stromal invasion, and tumor diameter between 2-4 cm. Sixty-six (47%) patients received RT alone, whereas 59 (42%) were treated with RT and concomitant chemotherapy (CT), and 16 received neoadjuvant CT. Patients with positive vaginal margins also received 27.5 Gy high-dose rate vaginal cuff brachytherapy in five fractions. Median follow-up time was 55 months. The actuarial 5-year overall (OS), disease-free (DFS), locoregional recurrence-free (LRFS), and distant metastases-free (DMFS) survival rates are 70%, 68%, 77%, and 88%, respectively. Univariate and multivariate analyses revealed that level and number of metastatic LNs and concomitant CT were unique significant prognostic factors for OS, DFS, and LRFS. Endometrial involvement, on the other hand, was proven to be significant for DFS and DMFS. Patients with less than three LN metastases or having only obturator LN involvement showed similar prognosis with their counterparts having no LN metastases. On the other hand, patients with either common iliac LN or more than three LN metastases had significantly worse outcome. Our results indicate that level and number of metastatic LNs are the most important prognostic factors determining the survival rates, and patients with upper lymphatic involvement or more than three metastatic LNs seem to need more effective treatment approaches.     

Patients with squamous cell versus adeno(squamous) carcinoma of the cervix, what factors determine the prognosis?

Patients with squamous cell carcinoma of the cervix FIGO stages IB to IV ( n = 306) were compared to patients with adeno(squamous) carcinoma ( n = 70). There was no difference between the mean ages of the groups. In the patients who underwent radical surgical treatment, whether or not in combination with radiotherapy ( n = 209), stepwise regression analysis showed that a positive lymph node status was the most unfavorable prognostic factor, followed by the histologic type (adeno(squamous) carcinoma) and the tumor diameter (> 3 cm). Vascular-space invasion had no additional prognostic value. Patient's age did not affect the prognosis. Distant metastases were not found to be more prevalent in the patients with adeno(squamous) carcinoma. In patients with adeno(squamous) carcinoma and positive lymph nodes, it is worth considering more intensive locoregional treatment than is usually prescribed for these patients and/or adjunctive chemotherapy, because there is a high risk of tumor recurrence.     

The prognostic implications of anaemia in the outcome of patients with early stages of uterine cervix carcinoma

 We studied the prognostic value of anaemia in the evolution of patients with early stages of uterine cervix cancer and treated with radical surgery. An observational study of 114 patients treated for cervical cancer at the ”La Fe” Maternity Hospital in Valencia (Spain) during the period 1971 to 1989. Survival analyses were carried out whereby both recurrence and mortality rates were considered. The level of haemoglobin influences the prognosis of the patients in the study presented, and explains a variation in the disease-free interval in correlation with that of tumour size. However, its influence on the survival interval proved to be somewhat less. Its predictive value is not diminished when associated with other important factors regarding the influence on patient evolution and is seen to be a protector variable against recurrence. Patients with haemoglobin levels of less than 13 gr/dl have a less favourable prognosis and this prognosis worsens still further when levels are lower than 12 gr/dl, which is more frequently the case in patients under 40 years of age and with a greater stromal invasion depth. The influence of haemoglobin levels is equally as important in its influence on prognosis and patient evolution as the volume of the tumour itself. The effect of this variable depends on both the clinical characteristics of the patients and the pathological characteristics of the tumour. Received: 17 October 2001 / Accepted: 28 December 2001     

Adjuvant radiotherapy in carcinomas of the uterine cervix: the prognostic value of hemoglobin levels

Anemia has been associated with a poorer treatment response and reduced survival in women undergoing primary radiotherapy (RT) or radiochemotherapy for advanced cervical carcinoma. This study aimed to determine the influence of anemia on outcome in patients with cervical carcinoma undergoing adjuvant RT. Medical records were reviewed for 183 cervical cancer patients who had received adjuvant RT because of risk factors after radical surgery (n= 109) or inadequate primary surgery (simple hysterectomy; n= 74). Kaplan-Meier and Cox regression analyses were used to study hemoglobin levels before and during adjuvant RT in relation to recurrence-free and overall survival. Hemoglobin values > or =11 g/dL were considered normal, while those <11 g/dL indicated anemia. Hemoglobin levels before RT influenced significantly overall survival and recurrence-free survival across the whole group (overall survival--log rank(all patients)= 7.5; df = 1; P= 0.006). However, subgroup analysis showed that the observed difference was mainly due to the group of women who had undergone inadequate primary surgery (overall survival--log rank(inadequate surgery)= 10.8; df = 1; P= 0.001). Multifactorial regression analyses comparing hemoglobin before RT with grading and tumor stage confirmed the prognostic value of hemoglobin values. Maintaining normal hemoglobin values before and during adjuvant RT seems to be important, especially in patients who have had inappropriate simple hysterectomy, which may resemble a therapeutic situation.     

Histological grading and DNA content as predictors of distant metastases in squamous cell carcinoma of the uterine cervix

Summary Squamous cell carcinoma of the uterine cervix with distant metastases can be treated by adjuvant chemotherapy. The at-risk patients are those with histologically proven metastases, the presence of tumour in paracervical tissue and parametrium, evidence of vascular invasion, a great depth of invasion, or poor tumour differentiation. Our studies lead us to believe that differentiation and DNA content are also important criteria.     

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%.     

子宫颈鳞状细胞癌复发患者血清鳞状细胞癌抗原监测的意义

目的探讨血清鳞状细胞癌抗原（SCCAg）在监测宫颈鳞癌患者复发中的意义。方法对1999-2005年收治的72例宫颈鳞癌复发患者血清SCCAg水平与诊断、预后的关系进行单因素和多因素分析。结果72例复发患者中,术后复发30例、放化疗后复发42例,其中血清SCCAg水平升高者61例（占85％）。此61例患者中,20例在随诊中首先出现血清SCCAg水平升高而临床及影像学检查未发现肿瘤,血清SCCAg水平提前升高的中位时间为3个月,平均4．6个月（1～13个月）。72例复发患者中,45例患者无任何临床症状,仅因血清SCCAg水平升高或常规随诊发现复发;27例患者有症状,其中单侧下肢水肿或疼痛15例,阴道不规则流血7例,出现远处转移相关症状5例。细胞或组织病理学检查诊断复发者33例;临床及影像学检查结合血清SCCAg水平诊断复发者39例,其中29例仅依靠血清SCCAg水平升高及影像学检查即诊断复发。72例复发患者的中位生存时间为11个月,平均生存时间为23个月（2～62个月）,总的3年生存率为25％,5年生存率为19％。单因素分析发现,初治前患者血清SCCAg水平、病理分级、复发部位、复发后治疗方式以及复发时、复发后治疗中、治疗后血清SCCAg水平对患者的3年生存率有明显影响（P〈0．01）;但20例血清SCCAg水平提前出现升高的患者与52例血清SCCAg水平未提前升高的患者相比,3年生存率分别为22％、27％,差异无统计学意义（P=0．5761）。多因素分析发现,复发患者仅病理分级、复发后的治疗方式是独立的预后影响因素（P〈0．05）;而复发部位及各种血清SCCAg状态不是独立的预后影响因素（P〉0．05）。结论血清SCCAg水平监测在宫颈鳞癌复发患者中的诊断及其对预后的判断中有一定的价值。     

Lymph node metastasis and lymph vascular space invasion in microinvasive squamous cell carcinoma of the uterine cervix

The objective of this study was to determine whether the depth of invasion was related to lymph vascular space invasion (LVSI) and lymph node metastasis and whether there was a correlation between LVSI and lymph node metastasis in stage IA cervical cancer. The medical records, including surgical notes and pathologic reports, of 202 patients with microinvasive squamous cell carcinoma of the uterine cervix were reviewed retrospectively. There was a positive correlation between the depth of invasion and the LVSI, and the incidence of lymph node metastasis was slightly higher than those reported hitherto for stage IA1 cervical cancer, especially in the depth of invasion of 1-3 mm group. However, among four patients with lymph node metastasis, only two patients had positive LVSI. There was no definite correlation between LVSI and lymph node metastasis. LVSI could not identify the patients with high risk for lymph node metastasis.