Pattern of lymph node metastasis and the optimal extent of pelvic lymphadenectomy in FIGO stage IB cervical cancer

AIM: To evaluate the distribution pattern of lymph node metastasis and to determine the optimal extent of pelvic lymphadenectomy (LA) in FIGO stage IB cervical cancer. METHODS: The medical records of 187 patients with FIGO stage IB cervical cancer from March 1996 to December 2002 were reviewed retrospectively. The distribution pattern and risk factors of lymph node metastases were analyzed in 31 patients with lymph node metastases confirmed surgically. One hundred patients, who underwent type III hysterectomy with pelvic LA but did not receive any adjuvant treatment, were analyzed to evaluate whether the extent of LA affected the prognosis of FIGO stage IB cervical cancer. Type I LA included the external iliac nodes, hypogastric nodes, obturator nodes, and parametrial nodes. Type II LA included the pelvic nodes described in type I LA, the common iliac nodes, gluteal nodes, deep inguinal nodes and sometimes the presacral nodes. RESULTS: Solitary lymph node metastasis confined to one node group was seen in the obturator, external iliac or hypogastric lymph nodes. All patients with lymph node metastases at multiple sites had metastasis in at least one of these lymph-node groups. There was no significant difference in disease-free survival and overall survival in patients without pathologic high-risk factors according to the type of pelvic LA. CONCLUSION: The extent of LA should be adjusted to reduce complications and not to affect adversely the prognosis of FIGO stage IB cervical cancer patients without pathologic high-risk factors.     

Treatment of cervical cancer with adjuvant chemotherapy versus adjuvant radiotherapy after radical hysterectomy and systematic lymphadenectomy

Aim:  To compare the clinical efficacy focused on post-treatment morbidity between adjuvant chemotherapy (CT) and pelvic radiotherapy (RT) after radical hysterectomy for patients with cervical cancer.
Methods:  A total of 125 patients with cervical squamous cell carcinoma who underwent radical hysterectomy and pelvic lymphadenectomy at Hokkaido University Hospital between 1991 and 2002 were enrolled in the study for retrospective analysis. Seventy patients with recurrent risk factors, including deep stromal invasion, lymph vascular space invasion, parametrial invasion, lymph node metastasis (LNM), and bulky tumor (≥4 cm), received adjuvant therapy; 42 were treated with RT, and 28 were treated with CT. Almost all patients with multiple LNM received RT. Analyses were also performed on a subgroup of 50 patients without multiple LNM (23 RT, 27 CT). Clinical efficacy of post-treatment morbidity and survival was evaluated.
Results:  Because there were more patients with multiple LNM in the RT group, we analyzed disease-free survival in 50 patients without multiple LNM. The 3-year disease-free survival rate was 82.6% with RT and 96.3% with CT ( P  = 0.16). Postoperative bowel obstruction was significantly more frequent in the RT group versus the CT ( P  = 0.007) and no-therapy ( P  = 0.0026) groups. Urinary disturbance was also more frequent in the RT group than in the CT ( P  = 0.0016) and no-therapy ( P  = 0.089) groups.
Conclusion:  CT has the equivalent therapeutic effect as RT with fewer postoperative complications for patients with intermediate risks. A prospective randomized trial is needed to compare CT combined with radical hysterectomy and pelvic lymphadenectomy to RT or chemoradiotherapy.     

Lymphvascular invasion in stage IB cervical carcinoma: prognostic significance and role of adjuvant radiotherapy

The Prognostic significance of lymphvascular invasion (LVI) in stage: IB cervix cancer remains controversial in spite of several recent reports in this literature. This report analyses the impact of LVI in patients undergoing surgery followed by postoperative radiation therapy.
The clinical-pathological records of 110 patients with stage IB carcinoma of the cervix cancer remains controversial in spite of several recent reports in this literature. This report analyses the impact of LVI in patients undergoing surgery followed bu postoperative radiation therapy.sessed for grade, positive margins, depth of invasion, positive nodes, and LVI. Only LVI showed a significant correlation ( P = 0.0002) with local failure. Thirty-two patients with squamous cell carcinoma and LVI were identified. Seventeen of these patients received postoperative radiotherapy and 15 patients received no adjuvant therapy. Both groups were traced for outcome. Four of the 15 patients (27%) with LVI treated with surgery alone developed local recurrence, compared to 0/17 patients who received postoperative radiotherapy ( P = 0.038). The 5-year and 7-year survival of the entire group was excellent, 97.2% and 94.9% respectively. There was a trend towards significance ( P = 0.07) in survival between LVI+ and LVI− patients.
Lymphvascular invasion was significantly associated with increased local failure in our analysis. Although prospective randomized trials are in progress to further evaluate this issue there is growing concern about low accrual because of physicians biases regarding this controversial issue. Adjuvant postoperative radiotherapy appears beneficial in improving local control for LVI patients in our study, but its impact on survival is still questionable. We recommend enrollment of patients in a national cooperative trial whenever possible. Treatment of patients off protocol solely for LVI+ is still quite controversial and must be left to the discretion of the clinician.     

Radical hysterectomy with adjuvant radiotherapy versus definitive radiotherapy alone for FIGO stage IIB cervical cancer

Objectives

The aim of this study was to compare the treatment outcomes and adverse effects of radical hysterectomy followed by adjuvant radiotherapy with definitive radiotherapy alone in patients with FIGO stage IIB cervical cancer.

Methods

We retrospectively reviewed the medical records of FIGO stage IIB cervical cancer patients who were treated between April 1996 and December 2009. During the study period, 95 patients were treated with radical hysterectomy, all of which received adjuvant radiotherapy (surgery-based group). In addition, 94 patients received definitive radiotherapy alone (RT-based group). The recurrence rate, progression-free survival (PFS), overall survival (OS), and treatment-related complications were compared between the two groups.

Results

Radical hysterectomy followed by adjuvant radiotherapy resulted in comparable recurrence (44.2% versus 41.5%, p = 0.77), PFS (log-rank, p = 0.57), and OS rates (log-rank, p = 0.41) to definitive radiotherapy alone. The frequencies of acute grade 3–4 toxicities were similar between the two groups (24.2% versus 24.5%, p = 1.0), whereas the frequencies of grade 3–4 late toxicities were significantly higher in the surgery-based group than in the RT-based group (24.1% versus 10.6%, p = 0.048). Cox multivariate analyses demonstrated that treatment with surgery followed by adjuvant radiotherapy was associated with an increased risk of grade 3–4 late toxicities, although the statistical significance of the difference was marginal (odds ratio 2.41, 95%CI 0.97–5.99, p = 0.059).

Conclusions

Definitive radiotherapy was found to be a safer approach than radical hysterectomy followed by postoperative radiotherapy with less treatment-related complications and comparable survival outcomes in patients with FIGO stage IIB cervical cancer.     

早期宫颈癌淋巴结转移规律的临床研究

目的 研究早期宫颈癌盆腔淋巴结转移的危险因素及规律,为其选择性淋巴结切除术和术后个性化放疗临床靶体积(clinical target volume,CTV)的勾画提供依据.方法 回顾性分析2009年1月至2015年12月湖南省肿瘤医院收治的7472例接受宫颈癌根治术的早期(Ⅰ A1～ⅡA2)宫颈癌患者的临床资料.结果 ...     

Tailoring adjuvant radiotherapy for stage IB-IIA node negative cervical carcinoma after radical hysterectomy and pelvic lymph node dissection using the GOG score

Objective

The use of adjuvant radiotherapy for early stage node negative patients varies for different institutions. The recognized factors such as deep stromal invasion, lymph vascular space invasion, and size of tumor are the most common factors cited for adjuvant radiotherapy. Studies done have shown that this increases local control but may increase chronic toxicity rates. We report on our use of the GOG score to tailor our treatment decisions.

Methods

A review of all patients staged IB–IIA who underwent Type 3 Radical Hysterectomy and pelvic lymph node dissection (RH) from 1997 to 2007. The GOG score proposed by Delgado et al. was applied, and patients were stratified into 3 groups; < 40: no adjuvant treatment, 40–120: Small Field RT (SmRT), and > 120: Standard Field RT (StRT)

Results

A total of 126 patients matched these criteria. Sixty one patients underwent either SmRT or StRT. There were only 2 known relapses and one death due to inter current illness. The median follow up was 57 months and the 5 year Disease Free Survival was 98.2%. There were no documented Grade 3 or 4 chronic toxicities. There were significantly less (p = 0.025) patients with lower limb lymphedema in the SmRT group compared to StRT.

Conclusion

Our study confirms the utility of the GOG score to tailor radiotherapy for this cohort of patients. This has been proven to be high in efficacy and low in morbidity.     

High cyclooxygenase-2 expression in stage IB cervical cancer with lymph node metastasis or parametrial invasion

OBJECTIVE: The enzymes cyclooxygenase (COX)-1 and -2 are necessary for the synthesis of prostaglandins. COX-2 is usually absent in normal cells and is upregulated and expressed as a product of the "immediate early" gene during inflammatory processes. In previous studies, the expression of COX-2 has been shown to be induced by proinflammatory cytokines, and suggestions have been made that overexpression of COX-2 suppresses apoptosis and is directly related to tumor growth. We have attempted to determine a relationship between tumor invasion and metastasis of uterine cervical cancer and COX and apoptosis by comparing the protein expression of apoptosis, COX-1, and COX-2 in tumor tissues. METHODS: The subjects were 36 patients who were FIGO stage IB uterine cervical cancer patients who underwent surgery at Ajou University Hospital. There were 12 cases with lymph node or parametrial involvement. All tissues were subjected to immunohistochemical staining for COX-1, -2, and TUNEL method for apoptosis detection, and the following results were obtained. RESULTS: Tumor tissues confirmed by cytokeratin were separated into tumor surface, tumor stroma, and invasion site portions, in which decreased apoptosis was observed in the invasion sites. COX-2 expression was observed in all tumor tissues and was especially strong in the tumor invasion site. Therefore, it is suggested that COX-2 expression may suppress cell apoptosis at the tumor invasion site. When COX-2 expression was investigated according to the groups with regard to the presence of lymph node or parametrial involvement, there was a statistically significant (Mann-Whitney U test) COX-2 expression difference in the tumor invasion site (P value = 0.040) and the tumor stroma (P value = 0. 028). CONCLUSIONS: In surgically treated stage IB cervical cancer patients, COX-2 was significantly expressed when lymph node or parametrial involvement was present. These results suggest that the expression of COX-2 in stage IB cervical cancer may downregulate apoptotic processes and thus enhance tumor invasion and metastasis.     

Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection

Abstract. Kim SM, Choi HS, Byun JS. Overall 5-year survival rate and prognostic factors in patients with stage IB and IIA cervical cancer treated by radical hysterectomy and pelvic lymph node dissection.
The objective of this paper was to analyze the 5-year survival rate and prognostic factors for stage Ib and IIa cervical cancer treated by radical hysterectomy. A total of 366 patients with invasive cervical cancer treated by radical hysterectomy from June 1985 to June 1994 at Chonnam National University Hospital, Kwangju, Korea were retrospectively analyzed. Survival analysis was performed using the Kaplan-Meier estimator. Multivariate analysis was performed using the Cox proportional hazards regression model. The overall 5-year survival rate was 92% in stage Ib and 87% in stage IIa. Factors assessed for prognostic value included age, FIGO stage, cell type, tumor size, depth of invasion, lymphovascular space invasion (LVSI), and pelvic lymph node metastases (LNM). In the multivariate analysis, age, cell type, and lymph node metastases were independent predictors of survival. Lower survival was associated with age greater than 50 years, adenocarcinoma, and presence of lymph node metastases. The higher survival rates in patients with single lymph node involvement or lymph node metastases below the level of the common iliac nodes (85 and 84.6%, respectively) versus multiple or extrapelvic lymph node metastases (50 and 20%, respectively) were statistically significant ( P < 0.01). In conclusion, patients who had lymph node metastases, adenocarcinoma, and were older than 50 years had a poorer survival rate. Such patients require more intense postoperative treatment and closer surveillance. Low-risk patients with a single lymph node metastasis below the level of the common iliac nodes may benefit from thorough lymphadenectomy without adjuvant therapy to prevent unpleasant complications.     

Drain-site metastasis after radical hysterectomy for squamous cervical cancer

Drain-site metastasis occurred after radical hysterectomy for squamous cervical cancer.     

The prognostic factors for patients with early cervical cancer treated by radical hysterectomy and postoperative radiotherapy

PURPOSE: This study was undertaken to evaluate the efficacy of postoperative radiotherapy (post-OP RT) and to investigate the prognostic factors for early-stage cervical cancer patients who were treated by radical surgery, and the pathological findings suggested a relatively high risk of relapse with surgery alone. MATERIALS AND METHODS: From January 1990 to December 1995, 222 patients with stage IB-IIA cervical cancer, treated by radical surgery and a full course of post-OP RT, were included in this study. The indications for post-OP RT were based on pathological findings, including lymph node metastasis, positive surgical margins, parametrial extension, lymphovascular permeation, and invasion of more than two-thirds of the cervical wall thickness. The radiation dose of external beam was 44-45 Gy to the whole pelvis and 50-54 Gy to the true pelvis. One hundred seventy-two patients also received intravaginal brachytherapy as a local boost. The minimal follow-up period was 2 years. RESULTS: The actuarial 5-year overall and disease-specific survival rates for all patients were 76 and 82%, respectively. The tumor control rate within the pelvis reached 94%, and distant metastasis was the major cause of treatment failure. Univariate analysis of clinical and pathological parameters revealed that clinical stage, bulky tumor size, positive lymph nodes, parametrial extension, and histologic type were significant prognostic factors. After multivariate analysis, only positive lymph nodes (P = 0.01), bulky tumor size (P = 0.02), and parametrial extension (P = 0.05) independently influenced the disease-specific survival (DSS). For patients with lymph node metastasis, the number and location of the nodal involvement significantly affected the prognosis. The 5-year DSS for patients with no, one, and more than one lymph node metastasis were 87, 84, and 61% (P = 0.0001), respectively. Patients with upper pelvic lymph node metastasis had a higher incidence of distant metastasis (50% vs 16% in lower pelvic node group, P = 0.03). In the subgroup of single lower pelvic nodal metastasis, the prognosis was similar to that of patients without lymph node involvement (5-year DSS 85% vs 87%, P = 0.71). CONCLUSION: Our results indicate that post-OP RT can achieve very good local control in stage IB-IIA cervical cancer patients whose pathological findings show risk features for relapse after radical surgery. The prognostic factors for treatment failure identified in this study can be used as selection criteria for clinical trials to test the effects of other adjuvant treatments, such as chemotherapy. Patients with a single lower pelvic lymph node metastasis have a relatively good prognosis and may not need adjuvant treatment beyond radiation therapy.     

Correlation of angiogenesis and recurrence-free survival of early stage cervical cancer patients undergoing radical hysterectomy with pelvic lymph node dissection

AIM: To assess the correlation between the intensity of tumor angiogenesis, expressed as microvessel density, and recurrence-free survival in patients with early stage cervical cancer. METHODS: In a historical cohort study of patients with early stage cervical cancer undergoing radical hysterectomy with pelvic lymph node dissection at Songklanagarind Hospital during January 1998-December 2004, histological slides were immunostained for factor VIII-related antigen. Microvessel density was scanned at low magnification to identify the area with the highest number of vessels. Stained microvessels were counted at high magnification (x200) in an examination area of 0.25 mm2. Microvessel density and other potential prognostic factors were considered as covariates in multivariate Cox-proportional hazards regression models to evaluate their association with recurrence-free survival. RESULTS: One hundred and sixty-four patients were included in the study, and 16 patients developed recurrent disease during follow-up. The overall 5-year recurrence-free survival was 86.9% (95% confidence interval [CI] 78.9-92.0). In the multivariate analysis, microvessel density (hazard ratio [HR], for > or =9 vs <6 vessels per high power field: 5.8, 95% CI 1.5-22.7; P = 0.013), tumor size (HR for maximum diameter > or =2 vs <2: 3.6, 95% CI 1.2-10.7; P = 0.017) and parity (HR for > or =3 vs <3: 3.6, 95% CI 1.2-10.7; P = 0.018) were identified as significant independent prognostic factors for recurrence-free survival. CONCLUSION: Microvessel density is an independent prognostic parameter for recurrence-free survival in patients with early stage cervical cancer. Microvessel density at or above the cut-off point of nine vessels per high power field had significantly poorer recurrence-free survival.     

Completed versus aborted radical hysterectomy for node-positive stage IB cervical cancer in the modern era of chemoradiation therapy

Objective

Debate continues about optimal management of patients with node-positive stage I cervical cancer. Our objective was to determine if patient outcomes are affected by radical hysterectomy in the modern era of adjuvant chemoradiation.

Methods

Cervical cancer patients diagnosed from 2000 to 2008 were identified. Demographics, therapy, clinicopathologic data, progression free survival (PFS), overall survival (OS), total radiation exposure, and grade 3-4 complications were analyzed by student t, Mann-Whitney, Fisher's exact, Kaplan-Meier, and log rank tests.

Results

This single-institution review evaluated forty-one of 334 (13.4%) patients scheduled to undergo radical hysterectomy that had gross nodal disease diagnosed intraoperatively. 15 underwent aborted radical hysterectomy following lymphadenectomy; the remaining 26 underwent radical hysterectomy and lymphadenectomy. Eleven patients undergoing radical hysterectomy underwent whole pelvic radiation therapy (WPRT) while 8 (30.7%) patients underwent WPRT and postoperative vaginal brachytherapy (BT) for local treatment secondary to close margins. All patients undergoing aborted radical hysterectomy underwent WPRT and BT. With mean follow-up of 42.3 months, there were no significant differences in urinary, gastrointestinal, or hematologic complications between groups. When comparing those undergoing radical hysterectomy to aborted radical hysterectomy, there were no significant differences in local recurrence (11.5% vs 26.7%, p = 0.39) or distant recurrence (19.2% vs. 33.3%, p = 0.45), PFS (74.9 months vs 46.8 months, p = 0.106), or OS (91.8 months vs 69.4 months, p = 0.886).

Conclusions

Treatment of patients with early stage cervical cancer and nodal metastasis may be tailored intraoperatively. Completion of radical hysterectomy and lymphadenectomy decreases radiation exposure without apparently compromising safety or outcome in the era of adjuvant chemoradiation.     

Effect of radiotherapy on pelvic lymph node metastasis in cervical cancer stages IB2–IVA: a retrospective analysis of two comparative series

Efficiency of radiotherapy in controlling lymph node metastasis is a controversial issue. A continuous series of 87 patients affected by cervical cancer stages IB2-IVA and treated using pelvic radiotherapy is presented. A retrospective comparison is made between two populations. In the two populations, a staging lymphadenectomy was carried out before the onset of the therapeutic program. In the first population (53 patients), the pelvic nodes only were dissected and in the second one (34 patients), the pelvic lymph nodes were left in place and the paraaortic nodes only were dissected. In both series, a completion surgery was performed after finalization of the radiotherapy. It was carried out at open abdomen in both series. It included a systematic pelvic dissection for the patients whose pelvic nodes had been intentionally left in place at the time of the initial staging lymphadenectomy. Both series were identical as far as classic risk factors were concerned (FIGO stage, maximal tumor diameter, lymphovascular space involvement). The radiotherapy administered to the pelvis was the same in both populations. The number of patients with pelvic lymph node metastasis was 21 (39.6%) in the first population versus 6 (17.6%) in the second one (P = 0.03). The percentage of positive lymph nodes among the retrieved lymph nodes was 18.94 in the first population versus 2.8 in the second one (P = 0.0001). Pelvic radiotherapy is likely to control most of the pelvic lymph node metastasis, but not all of them. Practical deductions and further developments are discussed.     

Class III vs class II radical hysterectomy in stage IB cervical carcinoma: a comparison of morbidity and survival

The classical Piver III and a modified class II radical hysterectomy were applied in stage IB patients with cervical cancer and were compared as to morbidity and disease-free survival (DFS). Class III was performed in a group of 68 cases and class II in 50. The mean observation period was 31 and 69 months respectively. Most of the prognostic factors (age, histology, grade, bulky tumors, lymph node (LN) metastases) were comparable in the two groups. Postoperative irradiation was given to 31% and 64% of the type III and II hysterectomy group respecitvely ( P <0.05). Perioperative morbidity (mean operative time, blood units transfused, febrile cases and hospital stay) was quite similar. Major complications (mainly voiding problems) were significantly more frequent in class III operation. However, DFS was higher (86.5% vs 76.5%, P <0.05) after class III hysterectomy. These data indicate that class III operation is a more morbid procedure but appears to be advantageous regarding survival. In order to reduce morbidity without compromising therapeutic results (tailoring the radicality), a better insight in the prognostic factors is necessary.