FIGO Stage IB Cervical Cancer Research Articles

Surgical resection margin including parametrium and vagina significantly correlates with survival of FIGO stage IB cervical cancer patients treated with radical hysterectomy: Multivariate analysis of 360 patients

Surgical resection margin including parametrium and vagina significantly correlates with survival of FIGO stage IB cervical cancer patients treated with radical hysterectomy: Multivariate analysis of 360 patients

Preoperative nomogram for individualized prediction of parametrial invasion in patients with FIGO stage IB cervical cancer treated with radical hysterectomy

Preoperative nomogram for individualized prediction of parametrial invasion in patients with FIGO stage IB cervical cancer treated with radical hysterectomy

Preoperative nomogram for prediction of microscopic parametrial infiltration in patients with FIGO stage IB cervical cancer treated with radical hysterectomy

ObjectiveThis study aimed to establish a nomogram to predict microscopic parametrial infiltration (PMI) by combining preoperative clinicopathologic factors in FIGO stage IB cervical cancer patients treated by radical hysterectomy (RH). MethodsWe retrospectively analyzed clinicopathologic data of 298 patients with FIGO stage IB cervical cancer treated by RH between February 2000 and March 2015. The nomogram was developed based on multivariate logistic regression analysis of preoperative clinicopathologic data. The accuracy and discriminative ability of the nomogram were evaluated by a concordance index and calibration curve. The low-risk group was predefined as having a predicted probability of PMI <10%. ResultsMultivariate analysis identified diameter-based tumor volume and disruption of the cervical stromal ring on magnetic resonance imaging, serum squamous cell carcinoma antigen level, and menopausal status as independent prognostic factors associated with PMI. The concordance index of the nomogram was 0.940 (95% CI, 0.908–0.967), and calibration plots revealed good agreement between the observed probabilities and nomogram-predicted probabilities (Hosmer Lemeshow test, p=0.574). The nomogram classified 200 out of 298 patients (67.1%) as low risk. In the low-risk group, the predicted probability of PMI was 3.5% and the actual PMI rate was 2.5% (5 out of 200). ConclusionsWe developed a preoperative nomogram predicting microscopic PMI in surgically treated FIGO stage IB cervical cancer patients. The probabilities derived from this nomogram may have the potential to provide valuable guidance for physicians regarding the primary management of FIGO stage IB cervical cancer patients.

Different patterns of tumor size and serum SCC antigen level for prediction of parametrial invasion in pre- and post-menopausal patients with FIGO stage IB cervical cancer

Different patterns of tumor size and serum SCC antigen level for prediction of parametrial invasion in pre- and post-menopausal patients with FIGO stage IB cervical cancer

Clinical tumor diameter and prognosis of patients with FIGO stage IB1 cervical cancer (JCOG0806-A)

ObjectiveIn order to determine indications for less radical surgery such as modified radical hysterectomy, the risk of pathological parametrial involvement and prognosis of FIGO stage IB1 cervical cancer patients undergoing standard radical hysterectomy with pre-operatively assessed tumor diameter ≤2cm were investigated. MethodsWe conducted a retrospective multi-institutional chart review of patients with FIGO stage IB1 cervical cancer who underwent primary surgical treatment between 1998 and 2002. The eligibility criteria for the analyses were (i) histologically-proven squamous cell carcinoma, adenocarcinoma or, adenosquamous cell carcinoma, (ii) radical hysterectomy performed, (iii) clinical tumor diameter data available by MR imaging or specimens by cone biopsy, and (iv) age between 20 and 70. Based on the clinical tumor diameter, patients were stratified into those with the following tumors: i) 2cm or less (cT≤2cm) and ii) greater than 2cm (cT>2cm). We expected 5-year OS of ≥95% and parametrial involvement <2–3% for patients with cT≤2cm who underwent radical hysterectomy. ResultsOf the 1269 patients enrolled, 604 were eligible for the planned analyses. Among these, 571 underwent radical hysterectomy (323 with cT≤2cm and 248 with cT>2cm). Parametrial involvement was present in 1.9% (6/323) with cT≤2cm and 12.9% (32/248) with cT>2cm. Five-year overall survivals were 95.8% (95% CI 92.9–97.6%) in cT≤2cm and 91.9% (95% CI 87.6–94.8%) in cT>2cm patients. ConclusionPatients with cT≤2cm had lower risk of parametrial involvement and more favorable 5-year overall survival. They could therefore be good candidates for receiving less radical surgery.

Pretreatment risk factors for parametrial involvement in FIGO stage IB1 cervical cancer.

ObjectiveAll patients with stage IB1 cervical cancer do not need to undergo parametrectomy. Some low-risk criteria for parametrial involvement (PI) have been proposed based on pathological findings. The aim of this study was to determine pretreatment risk factors for PI in stage IB1 cervical cancer.MethodsWe retrospectively reviewed 115 patients with stage IB1 cervical cancer who underwent radical hysterectomy or radical trachelectomy. Magnetic resonance imaging (MRI) was performed and serum concentrations of squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 125 (CA-125) were determined in all patients before initial treatment. The following pretreatment factors were investigated: histological variant, maximum tumor diameter, tumor volume (volume index), pelvic lymph node enlargement, and serum tumor markers. Logistic regression analysis was used to select the independent risk factors for PI.ResultsEighteen of the 115 patients (15.7%) were pathologically diagnosed with PI. Multivariate analysis confirmed the following independent risk factors for PI: MRI-based tumor diameter ≥25 mm (odds ratio [OR], 9.9; 95% confidence interval [CI], 2.1 to 48.1), MRI-based volume index ≥5,000 mm3 (OR, 13.3; 95% CI, 1.4 to 125.0), and positive serum tumor markers SCC-Ag ≥1.5 ng/mL or CA-125 ≥35 U/mL (OR, 5.7; 95% CI, 1.3 to 25.1). Of 53 patients with no risk factors for PI, none had PI.ConclusionLess radical surgery may become one of the treatment options for stage IB1 cervical cancer patients with MRI-based tumor diameter <25 mm, MRI-based volume index <5,000 mm3, and negativity for SCC-Ag and CA-125.

A cut-off value of 2 cm in tumor size is of prognostic value in surgically treated FIGO stage IB cervical cancer

ObjectivesLimited knowledge exists about the value of tumor size in surgically treated cervical cancer (CX) using a tumor size of 2cm as cut-off value. MethodsA total of 366 cases of CX FIGO stage IB who received upfront surgery were evaluated regarding tumor size, the prediction of pelvic lymph node involvement, and recurrence-free and overall survival during a median follow-up time of 94months. Tumors ≤2.0cm were defined as small, tumors 2.1–4.0cm as medium sized and those larger than 4cm as bulky disease. ResultsSmall tumors were seen in 28.7%, medium sized in 52.5% and bulky tumors in 18.9%. There was a significant higher frequency of pelvic lymph node involvement with increasing tumor size (13.3% vs. 23.4% vs. 43.5%, respectively; p<0.001) and an increase of recurrent disease (6.7% vs. 18.8% vs. 29.4%, respectively; p<0.001). The 5-year overall survival rate was significantly reduced with increasing tumor size (94.0% vs. 85.1% vs. 69.9%, respectively; p<0.001).Pelvic lymph node involvement and maximal tumor size were independent prognostic factors for both recurrence-free and overall survival in multivariate analysis. ConclusionsThe results support that tumor size is of prognostic impact in FIGO stage IB cervical carcinomas. A further substaging is suggested for tumors up to 4.0cm maximum dimension using a cut-off value of 2.0cm as discriminator. Patients with tumors ≤2.0cm may represent low risk disease.

Predicting Factors for Positive Vaginal Surgical Margin Following Radical Hysterectomy for Stage IB1 Carcinoma of the Cervix

To examine the incidence of positive vaginal surgical margins and determine the predicting factors following radical hysterectomy for stage IB1 carcinoma of the cervix. The clinical and histological data of 656 FIGO stage IB1 cervical cancer patients who had radical hysterectomy with bilateral pelvic lymphadenectomy (RHPL) from January 2003 to December 2012 were retrospectively reviewed and were analyzed for their association with a positive vaginal surgical margin. A p-value of < 0.05 was considered significant. Thirty-five patients (5.3%) had positive vaginal surgical margins following RHPL; 24 (3.7%) for intraepithelial lesions and 11 (1.7%) for carcinoma. On multivariate analysis, microscopic vaginal involvement by high-grade squamous intraepithelial lesion and/or carcinoma (adjusted odd ratio (OR) 186.8; 95% confidence interval (CI) 48.5-718.5) and squamous histology (OR 8.7; 95% CI 1.7-44.0), were significantly associated with positive vaginal surgical margin. Microscopic vaginal involvement by HSIL and/ or carcinoma are strong predictors for positive vaginal surgical margins for stage IB1 cervical cancer patients undergoing radical hysterectomy. Preoperative 'mapping' colposcopy or other strategies should be considered to ensure optimal vaginal resection.

Comparison of laparoscopic versus abdominal radical hysterectomy for bulky (≥ 3 cm) FIGO stage IB and IIA cervical cancer

Comparison of laparoscopic versus abdominal radical hysterectomy for bulky (≥ 3 cm) FIGO stage IB and IIA cervical cancer

Tumor-associated CD66b+ neutrophil and CD8+ lymphocyte densities as independent prognostic factors for recurrence in localized cervical cancer: Automated digital image analysis and observer-assisted stereological assessments.

5532 Background: The prognostic impact of tumor-associated immune cells in cervical cancer is unclear. Methods: Automated digital image analysis (DIA) software and observer-assisted stereological (OAS) assessments were used to obtain densities of immunostains for CD66b+ neutrophils, CD163+ macrophages, and CD8+lymphocytes in scanned whole slide images of tumor sections from 101 patients with FIGO stage IB and IIA cervical cancer. Primary end-point was recurrence-free survival (RFS). Results: The highest densities of CD66b+ neutrophils and CD163+ macrophages were observed by OAS in the peritumoral compartment (median 53.1 cells/mm2 and 1.3% area fraction, respectively). DIA required far less human resources than OAS assessments. We observed high correlations between DIA and OAS variables of corresponding parameters; spearman ρ was 0.79 for CD8+ lymphocytes , 0.85 for CD66b+ neutrophils, and 0.92 for CD163+ macrophages (all p &lt;0.0001). Hazard rates for DIA assessments in the global tumor area were comparable with the prognostically strongest OAS assessments in the peritumoral compartment. In multivariate analysis, high density of CD66b+ neutrophils (HR 2.6; 95% CI 1.2–5.7; p = 0.02), low density of CD8+ lymphocytes (HR 2.3; 95% CI 1.1–4.9; p = 0.03), and presence of lymph node metastases (HR 2.6; 95% CI 1.2–5.5; p = 0.02) were independent predictors of poor RFS, whereas FIGO stage and CD163+macrophage density were not. The CD66b/CD8 immunostain index obtained by DIA had excellent discriminatory power for each quartile with 5-year RFS of 92%, 80%, 65%, and 48% for quartile I (&lt;0.019), II (0.02-0.05), III (0.06-0.24), and IV (&gt;0.25), respectively (p = 0.001). Conclusions: High tumor-associated CD66b+ neutrophil and low CD8+ lymphocyte densities are independent prognostic factors for short recurrence-free survival in cervical cancer assessed by DIA and OAS. Combined CD66b+ neutrophil/CD8+ lymphocyte immunostain index obtained by DIA is a strong and cost-efficient prognostic variable with potential for routine application.

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer

ObjectiveThe objective of this study was to evaluate the potential risk factors associated with parametrial invasion and to identify preoperatively a subgroup of patients at low risk for parametrial involvement who could be appropriate candidates for less radical surgery in FIGO stage IB1 cervical cancer. MethodsWe retrospectively reviewed the medical records of 317 FIGO stage IB1 cervical cancer patients undergoing class III radical hysterectomy and bilateral pelvic lymphadenectomy. Clinocopathologic factors associated with parametrial invasion were analyzed and the risk criteria predicting parametrial involvement were calculated using a logistic regression model. ResultsOf 317 patients, 17 patients (5.4%) had parametrial involvement. Tumor size >3cm (OR, 3.80; [95% CI, 1.19–12.06]; p=0.02) and pelvic lymph node metastasis (OR, 3.02; [95% CI, 1.04–8.79]; p=0.04) were independent pathologic factors for parametrial invasion on multivariate analysis. Significant preoperative factors associated with parametrial involvement were tumor size >3cm (OR, 4.29; [95% CI, 1.43–12.89]; p<0.01) and serum SCC Ag level >1.40ng/mL (OR, 3.27; [95% CI, 1.11–9.69]; p=0.03). We identified 185 low-risk (tumor size≤3cm and SCC≤1.4ng/mL) and 132 high-risk (tumor size>3cm and/or SCC>1.4ng/mL) patients. The rates of parametrial involvement in low- and high-risk patients were 1.1% and 11.4%, respectively (p<0.01). ConclusionsIn this dataset, a model using tumor size and SCC Ag level is highly predictive of parametrial involvement in patients with stage IB1 cervical cancer and may identify candidates for less radical parametrial resection.

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer

A model for prediction of parametrial involvement and feasibility of less radical resection of parametrium in patients with FIGO stage IB1 cervical cancer

Robotics Versus Laparoscopic Radical Hysterectomy with Lymphadenectomy in Patients with Early Cervical Cancer: A Multicenter Study

The aim of this study was to retrospectively compare the safety, morbidity, and recurrence rate of total laparoscopic radical hysterectomy (TLRH) with lymphadenectomy and total robotic radical hysterectomy (RRH) with lymphadenectomy for early cervical carcinoma in a series of 99 consecutive women. We studied 99 consecutive patients with FIGO stage Ia1 (LVSI), Ia2, Ib1, Ib2, and IIa cervical cancer, 76 of whom underwent TLRH and 23 underwent RRH with pelvic lymph node dissection. Para-aortic lymphadenectomy, with the superior border of the dissection being the inferior mesenteric artery, was performed in all cases with positive pelvic lymph nodes discovered at frozen section evaluation. The mean blood loss was 157ml in the RRH group (95% confidence interval [95% CI] 50-400) and 95ml in the TLRH group (95% CI 30-500) (not significant [NS]). The median length of hospital stay was 3days in the RRH group (95% CI 2-7) and 4days in the TLRH group (95% CI 3-7) (NS). The mean operating time was 255min for the TLRH group (95% CI 182-415) compared with 323min in the RRH group (95% CI 161-433) (P<0.05). No significant difference was found between the 2groups when comparing the recurrence rate. Robotic radical hysterectomy can be considered a safe and effective therapeutic procedure for managing early-stage cervical cancer without significant differences, if compared with laparoscopic radical hysterectomy, in terms of the recurrence rate and intraoperative and postoperative complications, although multicenter randomized clinical trials with longer follow-up are necessary to evaluate the overall oncologic outcomes of this procedure.

Pregnancy after lymphadenectomy and neoadjuvant chemotherapy followed by radical vaginal trachelectomy in FIGO stage IB1 cervical cancer

To report a case of full-term delivery after laparoscopic lymphadenectomy and neoadjuvant chemotherapy followed by radical vaginal trachelectomy in bulky stage IB1 cervical cancer. Case report. University hospital. A 27-year-old woman with adenosquamous cervical cancer stage IB1 (4 cm in diameter) that was diagnosed in December 2005. She expressed a wish for fertility-sparing treatment. A laparoscopic pelvic and para-aortic lymphadenectomy was performed and showed no evidence of lymphatic metastasis. The patient subsequently received chemotherapy with Paclitaxel 200 mg/m2 and Cisplatin 100 mg/m2. The treatment cycle was repeated after 3 weeks with Cisplatin reduced to 50 mg/m2, because of creatinine-increase. Radical vaginal trachelectomy was then performed. After histologic examination, carcinoma of only 2 mm in diameter was found in the final specimen. Oncologic and fertility outcome after neoadjuvant chemotherapy and radical vaginal trachelectomy. The patient resumed a normal menstrual pattern 6 weeks after surgery. In December 2008, she conceived and carried and infant to full term. Antenatally, she reported no problems during pregnancy except for gestational insulin-dependent diabetes. She gave birth to a baby boy at 38 weeks' gestation by caesarean section. The newborn (weight, 3500 g; length, 52 cm; Apgar scores, 5/8/10; pH value, 7.28) was monitored in a neonatal ward for 24 hours. The patient is currently under outpatient review and has had 5 years of follow-up with no evidence of recurrence. Neoadjuvant chemotherapy followed by a fertility-sparing surgery may become a valuable option for women with bulky-stage cervical cancer who wish to preserve their fertility potential.

Oncologic Results and Surgical Morbidity of Laparoscopic Nerve-Sparing Radical Hysterectomy in the Treatment of FIGO Stage IB Cervical Cancer: Long-Term Follow-Up

The aim of this study was to evaluate a long-term follow-up data for oncologic results and surgical morbidity of a laparoscopic nerve-sparing radical hysterectomy (NSRH) in the treatment of FIGO stage IB cervical cancer. This was a retrospective study that comprised consecutive 125 patients with cervical cancer stage IB1 (n = 105) and IB2 (n = 20) who underwent a laparoscopic NSRH (Piver type III) by a gynecologic oncologist without selecting patients from January 1999 to December 2007. In regression analysis, the operating time (R linear = 0.311, P < 0.001) and estimated blood loss (R linear = 0.261, P < 0.001) were decreased, whereas the number of harvested pelvic lymph nodes (R linear = 0.250, P < 0.001) was increased. Seventeen patients (13.6%, 17/125) were found to have pelvic node metastasis. Para-aortic node metastasis had occurred in 2 patients (5.1%, 2/39). There were high urological complications (13/125, 10.4%) related to radical surgery. Forty-one patients (33%) needed transfusions. Positive surgical margins did not exist. Patients were able to self-void at a mean of 10.3 days postoperatively. The return rates to normal voiding function at postoperative 14 and 21 days were 92.0% and 95.2%, respectively. Thirteen patients (IB1 n = 9, IB2 n = 4) experienced a recurrence postoperatively. Six patients (IB1 n = 3, IB2 n = 3) died of recurrent disease. Five-year disease-free survival rates of cervical cancer IB1 and IB2 were 92% and 78%, respectively (P = 0.1772). Five-year overall survival rates of cervical cancer IB1 and IB2 were 96% and 83%, respectively (P = 0.0437). A laparoscopic NSRH for FIGO stage IB cervical cancer was comparable to open NSRH in terms of early recovery of bladder function. It did not compromise surgical radicality, but revealed high urological complications, long operating time, and much blood loss, compared with conventional radical hysterectomy. However, these surgical morbidities were corrected with increase in experiences.

Matched-case comparison for the efficacy of neoadjuvant chemotherapy before surgery in FIGO stage IB1-IIA cervical cancer

Objective To evaluate whether neoadjuvant chemotherapy before surgery (NCS) is more efficient than primary surgical treatment (PST) for improving clinical outcomes in FIGO stage IB1-IIA cervical cancer. Methods We conducted a matched-case comparison where 61 patients treated with NCS were matched to 183 treated with PST. We compared intermediate- and high-risk factors, the need of adjuvant radiotherapy, disease recurrence and survivals between NCS and PST. Patients with ≥ 2 intermediate- or ≥ 1 high-risk factors received adjuvant concurrent chemoradiation using cisplatin-based chemotherapy. Results NCS reduced more definitely intermediate- and high-risk factors than PST in stage IIA disease in spite of little difference of them in stage IB disease (large tumor size, 25% vs. 52.4%; deep stromal invasion, 57.1% vs. 82.1%; lymphovascular space invasion, 35.7% vs. 65.5%; parametrial invasion, 17.9% vs. 41.7%; p < 0.05). Moreover, ≥ 2 intermediate-risk factors were less common in NCS than PST despite no difference of the number of high-risk factors between the 2 treatments, which decreased the need of adjuvant radiotherapy in patients with stage IIA disease who received NCS (46.4% vs. 84.5%, p < 0.01). Although there were no differences in progression-free survival and disease recurrence between the 2 treatments, NCS led to poorer overall survival than PST in stage IIA disease with no difference of it in stage IB disease. Conclusions The efficacy between NCS and PST may be similar in FIGO stage IB cervical cancer. However, NCS can lead to poor prognosis despite the reduction of intermediate-risk factors and the need of adjuvant radiotherapy in FIGO stage IIA disease.

Laparoscopic pelvic anatomy of nerve‐sparing radical hysterectomy

Many reports regarding nerve-sparing radical hysterectomy have been published. However, most reports have been based on systematic descriptions via laparotomy or cadaver dissection. The aim of this work was to describe the pelvic anatomy of nerve-sparing radical hysterectomy via laparoscopy, with specific focus on the inferior hypogastric plexus. This study is based on 125 patients with FIGO stage IB cervical cancer who had undergone laparoscopic nerve-sparing radical hysterectomies since 1999. The inferior hypogastric plexus was demonstrated via laparoscopy and was comprised of afferent fibers from the sacral root (S2, S3, and S4), sacral sympathetic ganglion, and hypogastric nerve, and efferent fibers forming its vesical, uterovaginal, and rectal branches. During the dissection of the posterior leaf of the vesicouterine ligament, various vesical veins were identified. If the cut edge of an inferior vesical vein was pulled medially with upward traction, the vesical branches of the inferior hypogastric plexus were exposed and these were divided into medial and lateral branches. The magnified view of laparoscopy made it possible to dissect nerves and vessels meticulously and to secure a clear resection margin during the dissection of the deep part of the cardinal ligament, uterosacral ligament, and posterior leaf of the vesicouterine ligament.

The twenty-first century role of Piver-Rutledge type III radical hysterectomy and FIGO stage IA, IB1, and IB2 cervical cancer in the era of robotic surgery: a personal perspective

Type III radical hysterectomy reported in 1974 by Piver, Rutledge, and Smith is considered worldwide by many as the standard surgical therapy for invasive cervical carcinoma stage IB and IIA. With the increasing number of robotic surgeries being performed for early stage cervical cancer worldwide, the purpose of the paper is to present our personal perspective of the 21st century role of Piver-Rutledge type III radical hysterectomy for stage IB cervical cancer in the era of robotic surgery using the da Vinci robot.

Comparison of Laparoscopic and Abdominal Radical Hysterectomy for Patients with FIGO Stage Ib1 Cervical Cancer: A Nonrandomized Prospective Analysis

Comparison of Laparoscopic and Abdominal Radical Hysterectomy for Patients with FIGO Stage Ib1 Cervical Cancer: A Nonrandomized Prospective Analysis

A validation study of new risk grouping criteria for postoperative treatment in stage IB cervical cancers without high-risk factors: Rethinking the Gynecologic Oncology Group criteria

Objective The aim of this study was to verify whether the Gynecologic Oncology Group (GOG) criteria are valid in a different cohort of patients and to investigate simplified new criteria tailoring adjuvant radiation therapy in patients with intermediate-risk factors after radical hysterectomy. Study design We analyzed the data of 332 patients with FIGO stage IB cervical cancer who underwent radical hysterectomy between 1994 and 2007. Two hundred and twenty-five patients without high-risk factors (lymph node metastasis, parametrial invasion, or positive surgical margins) were identified and were classified into low-risk and high-risk groups according to the GOG criteria and new criteria based on combinations of intermediate-risk factors (large tumor size, deep stromal invasion, lymph-vascular space invasion). We evaluated the prognostic significance of both criteria. Results We identified 140 low-risk patients and 85 high-risk patients in the application of the GOG criteria. Low-risk patients had significantly better disease-free survival (DFS) ( P = 0.001) and overall survival (OS) ( P = 0.013) than high-risk patients. There were 145 low-risk patients and 80 high-risk patients on applying the new criteria. Low-risk patients had significantly better DFS ( P = 0.001) and OS ( P = 0.013) than high-risk patients. The receiver operating characteristic (ROC) curves showed that both criteria had similar performance for predicting which patients would have help from adjuvant therapy. Conclusion This study demonstrated that the GOG criteria were still valid in the different population, the simplified new criteria were convenient to apply in practice, and the performance of the new criteria was as good as the GOGs.