Tumor size and lymph node status determined by imaging are reliable factors for predicting advanced cervical cancer prognosis
- Authors:
- Published online on: March 5, 2015 https://doi.org/10.3892/ol.2015.3015
- Pages: 2218-2224
Abstract
Introduction
Cervical cancer is the third most common type of cancer in the United States. Similarly, in Korea, cervical cancer is the sixth most common malignancy in female individuals and, more specifically, the second most common malignancy in females aged 15–44 years (1). The treatment strategy selected for patients with cervical cancer is based on the International Federation of Gynecology and Obstetrics (FIGO) staging system (2). For instance, surgery is the primary treatment strategy for early stage cervical cancer (stages IA–IIA), while concurrent chemoradiotherapy (CCRT) is the primary treatment strategy for more advanced stages of cervical cancer (stages IIB–IVB) (3). Despite the application of CCRT resulting in significant improvements in the disease-free and overall survival rates of patients with advanced cervical cancer, the survival rates in these patients remain unsatisfactory (4–7). Therefore, adjunctive treatment strategies following CCRT may be considered to improve survival rates for patients with poor prognostic factors, although there are currently no definite treatment guidelines. Therefore, it is important to assess individual prognoses to determine the most effective treatment method. The prognoses of patients with cervical cancer are typically estimated using the FIGO staging system. However, the current FIGO clinical staging system has limited value due to individual variability in physical examinations and a lack of consideration of other important factors, including pathological parameters and lymph node (LN) metastasis (8). Therefore, considering prognostic factors other than the FIGO stage may be required for more accurate prediction of individual prognoses.
At present, numerous prognostic factors, including tumor size, LN involvement, age, pretreatment serum squamous cell carcinoma antigen (SCC-Ag) levels, parametrial invasion and deep stromal invasion (9–17), are used to predict the risk of disease recurrence. However, the majority of previously conducted studies assessed early stage cervical cancer, while only a relatively small number of studies were performed in advanced stage cervical cancer patients.
The aim of the present study was to identify predictors of survival among various clinical variables and identify independent prognostic factors in advanced cervical cancer.
Patients and methods
Patient characteristics
In total, 157 patients diagnosed with stages IIA–IVB cervical cancer, who were treated between January 2006 and December 2010, were retrospectively included in the present analysis. The clinical findings and laboratory results of the included patients were collected from electronic medical records from four Hallym Medical Centers in South Korea (Hallym University Sacred Heart Hospital, Anyang; Kangnam Sacred Heart Hospital, Seoul; Chuncheon Sacred Heart Hospital, Chuncheon; and Kangdong Sacred Heart Hospital, Seoul, Republic of Korea). The study was approved by the Institutional Review Boards of Hallym University Sacred Heart Hospital.
Cases of stage II cervical cancer were subdivided into stages IIA and IIB, according to the FIGO staging system. Although the FIGO staging system was revised in 2009 (2), the number of patients exhibiting cervical cancer of stage IIB or higher was not altered. In addition, tumor size was included as a variable, and cases of revised stage IIA cervical cancer were divided by clinically visible lesion size without affecting the results. The patients were classified into four serum SCC-Ag groups, including the ≤2, 2–5, 5–15 and >15 ng/ml groups. The tumor size was determined as the largest diameter of the primary tumor as measured by computed tomography (CT) or magnetic resonance imaging (MRI), and was categorized as ≤4, 4–6 or >6 cm. Parametrial involvement was determined by physical examination and hydronephrosis by CT scanning or intravenous pyelography. In addition, bladder/rectal invasion was diagnosed by cystoscopic or sigmoidoscopic biopsy, while pelvic/para-aortic LN metastasis was pathologically verified or defined as a nodal size of ≥1 cm using CT or MRI. Patients exhibiting pelvic and para-aortic LN involvement were included in the para-aortic LN-positive group. The number of LN metastases determined from the pathological biopsies was relatively small due to inoperable advanced cervical cancer cases; thus, imaging identification of LN metastases was used as a variable. In addition, high-risk human papilloma virus (HPV) infection was observed using DNA microarray analysis.
Cancer treatment strategies
Of the 157 patients included in the study, 76 were treated with CCRT, 26 with surgery and chemotherapy, 23 with surgery and CCRT and the remaining 32 patients were treated using alternative methods. The patients treated with alternative methods were excluded from the current study due to the low sample number in each treatment group.
Surgical procedures included a radical hysterectomy with pelvic and/or para-aortic LN dissection for patients with stage IIA cervical cancer. Patients receiving CCRT were administered with six weekly infusions of cisplatin (40 mg/m2). Patients with a glomerular filtration rate of <60 ml/min were treated with carboplatin (120 mg/m2); however, if the leukocyte count of the patient reduced to <3,000/m3 or the platelet count decreased to <100,000/m3, the treatment was terminated. Following the completion of chemotherapy, the patients undergoing CCRT received external beam radiation therapy (EBRT) to the entire pelvis using ≤50.4 Gy with a 10 MeV photon and the four-field box technique. Daily doses of EBRT were administered in five fractions/week at 1.8 Gy per fraction. Following EBRT, the patients undergoing radical CCRT received additional EBRT, as well as high-dose intracavitary brachytherapy with iridium-192, in which the dose to point A was 30 Gy in six fractions. When para-aortic LN metastasis was suspected, the patients received extended field radiation therapy with a total dose of 55–60 Gy. Furthermore, patients receiving chemotherapy were administered combination therapy with paclitaxel (135 mg/m2, 24 h infusion on day 1) and cisplatin (50 mg/m2, 1 h infusion on day 2) every three weeks.
Following completion of the therapy, the patients underwent follow-up examinations every three months for the initial two years, every six months for the next three years and annually thereafter. The overall survival was assessed from the point of diagnosis to the point of mortality caused by the specific disease or the date of the final follow-up visit.
Statistical analysis
Kaplan-Meier analysis was used to calculate the disease-specific survival rate from the date of the initial treatment session to the date of disease-specific mortality. Differences in survival rates between the groups were compared using the log-rank test for categorical variables. In addition to the inclusion of age as a continuous covariate, variables identified as significant by univariate analysis were subsequently analyzed using the multivariate Cox proportional hazard model to clarify the association between overall survival and the identified risk factors. P<0.05 was considered to indicate a statistically significant difference and all statistical analyses were performed using the SAS software (version 9.2; SAS Institute Inc., Cary, NC, USA).
Results
Patient characteristics
The clinical characteristics of the patients included in the present multi-institutional study are summarized in Table I. The mean age of the patients at presentation was 57.52±14.06 years.
 | Table I.Clinical, treatment and outcome characteristics of 157 patients with cervical cancer treated between January 2006 and December 2010. |
Univariate analysis of 12 clinical factors
The Cox proportional hazards model was applied to analyze 12 factors, including age, tumor stage, SCC-Ag level, tumor size, parametrial involvement, lower third vaginal involvement, hydronephrosis, bladder/rectal involvement, LN metastasis detected by imaging, LN metastasis detected by pathology, HPV infection and tumor cell type, which were considered to have a prognostic value. Of these factors, the following eight variables demonstrated significantly high relative risk (RR; Table II), in order of decreasing RR: Lower third vaginal involvement (RR, 12.976), pathological LN metastasis (RR, 10.971), tumor size of >6 cm (RR, 8.691), LN metastasis (para-aortic and/or pelvic) detected by imaging (RR, 8.214), hydronephrosis (RR, 3.740), bladder/rectal involvement (RR, 3.216), SCC-Ag of >15 ng/ml (RR 2.480) and tumor stage (RR, 2.228).
| Table II.Cox proportional hazards model for survival of 12 factors considered to have a prognostic value in patients with advanced cervical cancer. |
Furthermore, significant predictive roles were identified for the following eight factors: i) Stage (P<0.0001); ii) tumor size (≤4 vs. 4–6 cm, P=0.0147; and ≤4 vs. >6 cm, P<0.0001); iii) SCC-Ag level of ≤2 vs. >15 ng/ml (P=0.0291); iv) lower third vaginal involvement (P<0.0001); v) hydronephrosis (P=0.0003); vi) bladder/rectal involvement (P=0.0015); vii) pelvic (P=0.0017) or para-aortic (P=0.0019) LN metastasis detected by imaging vs. no metastasis; and viii) pelvic LN identified by pathological analysis (P=0.0289).
Multivariate analysis of clinical factors
Of the eight factors identified as significant by univariate analysis, lower third vaginal involvement, hydronephrosis and bladder/rectal involvement were excluded from multivariate analysis as they are included in the FIGO staging system. In addition, LN metastasis detected by pathology was excluded due to the small number of cases available for analysis (n=46). However, age was included due to its marginal significance and clinical relevance.
The results of the multivariate analysis are summarized in Table III. The RR values were found to be 1.233 [95% confidence interval (CI), 0.918–1.686; P=0.1589] for patient age and 1.460 (95% CI, 0.964–2.210; P=0.0739) for tumor stage. Furthermore, the RR values for ≤2, 2–5, 5–15 and >15 ng/ml SCC-Ag were 1.000, 0.519 (95% CI, 0.153–1.760; P=0.2921), 0.458 (95% CI, 0.149–1.402; P=0.1712) and 0.944 (95% CI, 0.378–2.360; P=0.9022), respectively. In addition, the RR values for tumor sizes of ≤4, 4–6 and >6 cm were 1.000, 3.421 (95% CI, 1.077–10.872; P=0.0371) and 6.599 (95% CI, 1.952–22.311; P=0.0024), respectively. In LN metastasis detected by imaging, the RR values were 2.319 (95% CI, 1.000–5.376; P=0.0499) for positive pelvic LN and 3.204 (95% CI, 0.561–18.302; P=0.1902) for positive para-aortic LN.
| Table III.Multivariate Cox proportional hazards model for survival in advanced cervical cancer patients. |
Of the five factors analyzed, the following two were determined as independent predictive variables by multivariate analysis: i) Tumor size (≤4 vs. 4–6 cm, P=0.0371; and ≤4 vs. >6 cm, P=0.0024); and ii) pelvic LN metastasis detected by imaging vs. no metastasis (P=0.0499). By contrast, para-aortic LN metastasis (P=0.1902), age (P=0.1589), tumor stage (P=0.0739) and serum SCC-Ag level (P>0.1712) were not found to be independent predictive factors.
Survival analysis
In the current study, the median follow-up period was 55 months (range, 12–70 months), the median survival rate was 33.0 months and the mean survival rate was 44.5 months. The Kaplan-Meier method was applied to determine the duration of patient survival according to each of the investigated variables. Significantly different mean survival rates were identified among the various tumor stages (Fig. 1), including 39.91 months for stage IIA, 50.60 months for stage IIB, 14.34 months for stage III and 28.67 months for stage IV (log-rank test, P<0.0001). Although the mean survival duration was significantly different, marked overlapping of the survival durations were observed between stages IIA and IIB, and stages IIIA/B and IVA/B of cervical cancer.
Statistically significant differences in survival were identified according to tumor size and the presence of LN metastasis (Fig. 2). For instance, the mean survival rates of patients with a maximum tumor diameter of ≤4, 4–6 and >6 cm were 66.1, 50.3 and 38.3 months, respectively (log-rank test, P<0.001). Furthermore, the mean survival rates of patients with no LN, pelvic LN and para-aortic LN metastases were 60.9, 49.3 and 22.0 months, respectively (log-rank test, P=0.001). No overlapping in survival duration was identified according to these variables.
Discussion
The FIGO staging system is widely used to select the appropriate treatment strategy and predict the prognosis for cervical cancer (2). Accurate staging of cervical cancer is essential for therapeutic decision-making, determining the prognosis and comparing the results of different treatment modalities (2). However, the current FIGO clinical staging system has limited prognostic accuracy and an increased possibility of staging errors in patients with advanced disease (18–20). Thus, the prognosis of patients with advanced cervical cancer appears to be variable, even among patients at the same stage (17,21). In the present study, a significant overlap of survival duration was observed between cervical cancer stages IIA and IIB, as well as stages IIIA/B and IVA/B (Fig. 1), demonstrating the difficulty of accurately predicting survival using stage alone in advanced cervical cancer cases.
Furthermore, the FIGO staging system does not include pathological factors, such as tumor size and LN involvement, which are established prognostic factors (6,13,18–22). Thus, developing a novel tool for accurate prognostic prediction in advanced cervical cancer is essential.
As tumor size is closely associated with prognosis, the preoperative division of stage IIA into substages IIA1 and IIA2 has been attempted based on clinical measurements of the maximum tumor diameter (2). The tumor size is reflected in FIGO stages IA–IIA, but not in stage IIB or higher, from which suffered a number of the subjects in the present study. As a consequence, tumor size was analyzed as a prognostic factor in the current study. Classifying tumors into stages IIB1 and IIB2 based on a tumor size of >6 cm was not found to be appropriate for stage IIB cancer.
The Cox proportional hazards model was used to analyze factors considered to be associated with the prognosis of cervical cancer. Significant variables with high RR were identified as follows: Lower third vaginal involvement (RR, 12.976), pathological LN metastasis (RR, 10.971), LN metastasis (para-aortic and/or pelvic) detected by imaging (RR, 8.214), tumor size of >6 cm (RR, 8.691), hydronephrosis (RR, 3.740), bladder/rectal involvement (RR, 3.216) and tumor stage (RR, 2.228). Among these variables, lower third vaginal involvement was associated with a greater risk of poor prognosis compared with bladder/rectal involvement, resulting in uncertainty regarding the reliability of lower third vaginal and bladder/rectal involvement as requirements for FIGO stages IIIB and IVA, respectively. Improvements in palliative treatment, including percutaneous nephrostomy, diversion cystostomy/colostomy and neoadjuvant chemotherapy, may have affected these survival results (23–25).
The involvement of HPV in cervical cancer development is well-established; however, attempts to determine the prognostic significance of the presence or absence of HPV DNA in patients with cervical cancer have yielded conflicting results (26–29). HPV-negative cervical carcinoma was associated with poor survival in a number of reports (26–29), but not in other studies (30,31). Furthermore, high-risk HPV infection is an important and well-established risk factor for cancer development, with a previous study identifying high-risk HPV infection as an independent prognostic factor in early stage cervical cancer (32). However, the present study identified no statistically significant correlation between high-risk HPV infection and cervical cancer prognosis (P=1.0000). This indicates that HPV infection may be associated with prognosis in early but not advanced-stage cervical cancer.
The specific tumor cell type of cervical cancer has been investigated (12). Previous studies have demonstrated that early and advanced stage adenocarcinomas are more aggressive and associated with decreased survival rates (33–36). However, the present study indicated that the tumor cell type was not significantly associated with prognosis (P=0.5831).
Based on the results of the present study, the association between the overall survival and prognostic factors in stage IIA or higher cervical cancer patients are as follows: Survival analysis determined that tumor sizes of >6 cm (P=0.0024) and pelvic LN metastasis detected by imaging (P=0.0499) were independent factors of advanced-stage cervical cancer. Preoperative staging or pretreatment evaluation by CT or MRI have previously been demonstrated as predictive factors (36,37) and are commonly performed, indicating that it may be clinically acceptable to investigate tumor size and LN status by imaging. Thus, based on the present data, it is proposed that the inclusion of tumor size and imaging detection of pelvic LN metastasis in a future FIGO staging system may improve the accuracy of survival prediction. In addition, cancer stage has not been previously identified as an independent risk factor in early stage cervical cancer (22). The results of the present study demonstrated that cancer stage is not an independent risk factor in advanced-stage cervical cancer (P=0.0739) and, thus, verifying that the FIGO stage alone is not an accurate method for predicting the prognosis of advanced cervical cancer. Therefore, modification of the currently employed advanced cervical cancer staging system is required. Furthermore, an SCC-Ag level of >15 ng/ml was associated with survival in univariate analysis; however, it was not identified as an independent variable in the multivariate analysis. Previous studies have reported that SCC-Ag levels were associated with FIGO stage, tumor volume and the risk of developing LN metastasis (38,39); therefore, SCC-Ag may not be an independent risk factor, but is associated with survival. In addition, data from the present study did not support that the age at diagnosis is a prognostic factor, contrary to previous studies (11–13,40). The revised FIGO staging system is considered to provide more accurate details for dividing stage IIA cervical cancer into stages IIA1 and IIA2, according to a tumor size of 4 cm. In addition, the present authors consider it necessary for stages III and IV to be divided into substages according to the tumor size.
However, the current study presents a number of limitations. The first limitation is that the LN status was determined by CT or MRI imaging, despite the accuracy of LN metastasis detection by CT or MRI varying between 75–86 and 75–100%, respectively, and thus potentially biasing the current results (41). To eliminate this bias, determination of the LN status by pathological examination is required. However, staging surgery in patients with advanced stage cervical cancer is associated with potential morbidity. Recently, positron emission tomography (PET)-CT has been proven to be a useful tool for detecting LN metastasis with high sensitivity and specificity (42); thus, assessment of LN status using PET-CT may aid in reducing bias. The second limitation is that the present study included 33 patients with small cell carcinoma, adenocarcinoma and adenosquamous cell carcinoma, which are more likely to metastasize compared with other nonsquamous cell carcinoma histological types. Inclusion of these patients may have influenced the estimation of other prognostic variables, including the HPV infection status, SCC-Ag levels and age. Another limitation is the fact that patients underwent various treatment strategies (including, surgery plus chemotherapy, surgery plus CCRT and CCRT alone), which may have potentially influenced the survival analysis in the present study. In addition, the HPV types were not analyzed, since HPV typing was not available at Kangdong Sacred Heart Hospital or Kangnam Sacred Heart Hospital during the study period. Finally, the significance of the present study is limited due to its retrospective nature and small number of patients included. These limitations may be overcome by conducting a large sample size randomized trial.
In conclusion, accurately predicting survival rates in advanced cervical cancer is difficult using the stage alone. In the present study, tumor size and pelvic LN metastasis determined by CT and/or MRI were identified as independent predictive factors for the prognosis of stage II–IV cervical cancer. These factors may provide more clinically significant prognostic data compared with the currently used FIGO staging system.
Acknowledgements
This abstract was presented at the 15th Biennial Meeting of the International Gynecologic Cancer Society, November 8-11, 2014, Melbourne, Australia, and published as abstract no. IGCSM-0886 in the International Journal of Gynecological Cancer, Volume 24, Issue 9, 2014.
References
|
Ferlay J, Soerjomataram I, Ervik M, et al: GLOBOCAN 2008: Cancer incidence, mortality and prevalence worldwide. IARC Press; Lyon: 2008 | |
|
Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet. 105:103–104. 2009. View Article : Google Scholar : PubMed/NCBI | |
|
Lilic V, Lilic G, Filipovic S, Milosevic J, Tasic M and Stojilijkovic M: Modern treatment of invasive carcinoma of the uterine cervix. J BUON. 14:587–592. 2009.PubMed/NCBI | |
|
Keys HM, Bundy BN, Stehman FB, et al: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med. 340:1154–1161. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Morris M, Eifel PJ, Lu J, et al: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med. 340:1137–1143. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Rose PG, Bundy BN, Watkins EB, et al: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 340:1144–1153. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Whitney CW, Sause W, Bundy BN, et al: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol. 17:1339–1348. 1999.PubMed/NCBI | |
|
Kupets R and Covens A: Is the International Federation of Gynecology and Obstetrics staging system for cervical carcinoma able to predict survival in patients with cervical carcinoma?: an assessment of clinimetric properties. Cancer. 92:796–804. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Noguchi H, Shiozawa I, Sakai Y, Yamazaki T and Fukuta T: Pelvic lymph node metastasis of uterine cervical cancer. Gynecol Oncol. 27:150–158. 1987. View Article : Google Scholar : PubMed/NCBI | |
|
Avall-Lundqvist EH, Sjövall K, Nilsson BR and Eneroth PH: Prognostic significance of pretreatment serum levels of squamous cell carcinoma antigen and CA 125 in cervical carcinoma. Eur J Cancer. 28A:1695–1702. 1992. View Article : Google Scholar : PubMed/NCBI | |
|
Rutledge FN, Mitchell MF, Munsell M, Bass S, McGuffee V and Atkinson EN: Youth as a prognostic factor in carcinoma of the cervix: a matched analysis. Gynecol Oncol. 44:123–130. 1992. View Article : Google Scholar : PubMed/NCBI | |
|
Kosary CL: FIGO stage, histology, histologic grade, age and race as prognostic factors in determining survival for cancers of the female gynecological system: an analysis of 1973–87 SEER cases of cancers of the endometrium, cervix, ovary, vulva, and vagina. Semin Surg Oncol. 10:31–46. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Brewster WR, DiSaia PJ, Monk BJ, Ziogas A, Yamada SD and Anton-Culver H: Young age as a prognostic factor in cervical cancer: results of a population-based study. Am J Obstet Gynecol. 180:1464–1467. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Ishikawa H, Nakanishi T, Inoue T and Kuzuya K: Prognostic factors of adenocarcinoma of the uterine cervix. Gynecol Oncol. 73:42–46. 1999. View Article : Google Scholar : PubMed/NCBI | |
|
Wagenaar HC, Trimbos JB, Postema S, et al: Tumor diameter and volume assessed by magnetic resonance imaging in the prediction of outcome for invasive cervical cancer. Gynecol Oncol. 82:474–482. 2001. View Article : Google Scholar : PubMed/NCBI | |
|
Miller TR and Grigsby PW: Measurement of tumor volume by PET to evaluate prognosis in patients with advanced cervical cancer treated by radiation therapy. Int J Radiat Oncol Biol Phys. 53:353–359. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Tseng JY, Yen MS, Twu NF, et al: Prognostic nomogram for overall survival in stage IIB-IVA cervical cancer patients treated with concurrent chemoradiotherapy. Am J Obstet Gynecol. 202:174. e171–177. 2010. | |
|
Van Nagell JR Jr, Roddick JW Jr and Lowin DM: The staging of cervical cancer: inevitable discrepancies between clinical staging and pathologic findinges. Am J Obstet Gynecol. 110:973–978. 1971.PubMed/NCBI | |
|
Averette HE, Ford JH Jr, Dudan RC, Girtanner RE, Hoskins WJ and Lutz MH: Staging of cervical cancer. Clin Obstet Gynecol. 18:215–232. 1975. View Article : Google Scholar : PubMed/NCBI | |
|
Lagasse LD, Creasman WT, Shingleton HM, Ford JH and Blessing JA: Results and complications of operative staging in cervical cancer: experience of the Gynecologic Oncology Group. Gynecol Oncol. 9:90–98. 1980. View Article : Google Scholar : PubMed/NCBI | |
|
Seo Y, Yoo SY, Kim MS, et al: Nomogram prediction of overall survival after curative irradiation for uterine cervical cancer. Int J Radiat Oncol Biol Phys. 79:782–787. View Article : Google Scholar : PubMed/NCBI | |
|
Behtash N, Karimi Zarchi M and Deldar M: Preoperative prognostic factors and effects of adjuvant therapy on outcomes of early stage cervical cancer in Iran. Asian Pac J Cancer Prev. 10:613–618. 2009.PubMed/NCBI | |
|
Angioli R, Plotti F, Montera R, et al: Neoadjuvant chemotherapy plus radical surgery followed by chemotherapy in locally advanced cervical cancer. Gynecol Oncol. 127:290–296. 2012. View Article : Google Scholar : PubMed/NCBI | |
|
Lapitan MC and Buckley BS: Impact of palliative urinary diversion by percutaneous nephrostomy drainage and ureteral stenting among patients with advanced cervical cancer and obstructive uropathy: a prospective cohort. J Obstet Gynaecol Res. 37:1061–1070. 2011. View Article : Google Scholar : PubMed/NCBI | |
|
Sardi JE, Giaroli A, Sananes C, et al: Long-term follow-up of the first randomized trial using neoadjuvant chemotherapy in stage Ib squamous carcinoma of the cervix: the final results. Gynecol Oncol. 67:61–69. 1997. View Article : Google Scholar : PubMed/NCBI | |
|
Harima Y, Sawada S, Nagata K, Sougawa M and Ohnishi T: Human papilloma virus (HPV) DNA associated with prognosis of cervical cancer after radiotherapy. Int J Radiat Oncol Biol Phys. 52:1345–1351. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Riou G, Favre M, Jeannel D, Bourhis J, Le Doussal V and Orth G: Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA. Lancet. 335:1171–1174. 1990. View Article : Google Scholar : PubMed/NCBI | |
|
Higgins GD, Davy M, Roder D, Uzelin DM, Phillips GE and Burrell CJ: Increased age and mortality associated with cervical carcinomas negative for human papillomavirus RNA. Lancet. 338:910–913. 1991. View Article : Google Scholar : PubMed/NCBI | |
|
Ikenberg H, Sauerbrei W, Schottmüller U, Spitz C and Pfleiderer A: Human papillomavirus DNA in cervical carcinoma - correlation with clinical data and influence on prognosis. Int J Cancer. 59:322–326. 1994. View Article : Google Scholar : PubMed/NCBI | |
|
Rose BR, Thompson CH, Cossart YE, Elliot PE and Tattersall MH: Papillomavirus DNA and prognosis in cervical cancer. Lancet. 337:4891991. View Article : Google Scholar : PubMed/NCBI | |
|
Lombard I, Vincent-Salomon A, Validire P, et al: Human papillomavirus genotype as a major determinant of the course of cervical cancer. J Clin Oncol. 16:2613–2619. 1998.PubMed/NCBI | |
|
Burger RA, Monk BJ, Kurosaki T, et al: Human papillomavirus type 18: association with poor prognosis in early stage cervical cancer. J Natl Cancer Inst. 88:1361–1368. 1996. View Article : Google Scholar : PubMed/NCBI | |
|
Nakanishi T, Ishikawa H, Suzuki Y, Inoue T, Nakamura S and Kuzuya K: A comparison of prognoses of pathologic stage Ib adenocarcinoma and squamous cell carcinoma of the uterine cervix. Gynecol Oncol. 79:289–293. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Eifel PJ, Burke TW, Morris M and Smith TL: Adenocarcinoma as an independent risk factor for disease recurrence in patients with stage IB cervical carcinoma. Gynecol Oncol. 59:38–44. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Sigurdsson K, Hrafnkelsson J, Geirsson G, Gudmundsson J and Salvarsdóttir A: Screening as a prognostic factor in cervical cancer: analysis of survival and prognostic factors based on Icelandic population data, 1964–1988. Gynecol Oncol. 43:64–70. 1991. View Article : Google Scholar : PubMed/NCBI | |
|
Hricak H, Gatsonis C, Chi DS, et al: American College of Radiology Imaging Network 6651; Gynecologic Oncology Group 183: Role of imaging in pretreatment evaluation of early invasive cervical cancer: results of the intergroup study American College of Radiology Imaging Network 6651 - Gynecologic Oncology Group 183. J Clin Oncol. 23:9329–9337. 2005. View Article : Google Scholar : PubMed/NCBI | |
|
Subak LL, Hricak H, Powell CB, Azizi L and Stern JL: Cervical carcinoma: computed tomography and magnetic resonance imaging for preoperative staging. Obstet Gynecol. 86:43–50. 1995. View Article : Google Scholar : PubMed/NCBI | |
|
Gadducci A, Tana R, Cosio S and Genazzani AR: The serum assay of tumour markers in the prognostic evaluation, treatment monitoring and follow-up of patients with cervical cancer: a review of the literature. Crit Rev Oncol Hematol. 66:10–20. 2008. View Article : Google Scholar : PubMed/NCBI | |
|
Takeda M, Sakuragi N, Okamoto K, et al: Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix. Acta Obstet Gynecol Scand. 81:451–457. 2002. View Article : Google Scholar : PubMed/NCBI | |
|
Kapp DS, Fischer D, Gutierrez E, Kohorn EI and Schwartz PE: Pretreatment prognostic factors in carcinoma of the uterine cervix: a multivariable analysis of the effect of age, stage, histology and blood counts on survival. Int J Radiat Oncol Biol Phys. 9:445–455. 1983. View Article : Google Scholar : PubMed/NCBI | |
|
Boss EA, Barentsz JO, Massuger LF and Boonstra H: The role of MR imaging in invasive cervical carcinoma. Eur Radiol. 10:256–270. 2000. View Article : Google Scholar : PubMed/NCBI | |
|
Kidd EA, El Naqa I, Siegel BA, Dehdashti F and Grigsby PW: FDG-PET-based prognostic nomograms for locally advanced cervical cancer. Gynecol Oncol. 127:136–140. 2012. View Article : Google Scholar : PubMed/NCBI |
