Effectiveness of adjuvant systemic chemotherapy for intermediate-risk stage IB cervical cancer.
ABSTRACT: To examine the effectiveness of systemic chemotherapy following radical hysterectomy for women with intermediate-risk stage IB cervical cancer.This is a retrospective analysis of a previously organized nation-wide cohort study examining 6,003 women with stage IB-IIB cervical cancer who underwent radical hysterectomy between 2004 and 2008 in Japan. Survival of 555 women with stage IB cervical cancer in the intermediate-risk group (deep stromal invasion > 50%, large tumor size > 4 cm, and lympho-vascular space invasion [LVSI]) were examined based on adjuvant therapy patterns: chemotherapy alone (n = 223, 40.2%), concurrent chemo-radiotherapy (n = 172, 31.0%), and radiotherapy alone (n = 160, 28.8%).The most common intermediate-risk pattern was LVSI with deep stromal invasion (n = 216, 38.5%). The most common chemotherapeutic choice was taxane/platinum (52.2%). Women with adenocarcinoma/adenosquamous histology were more likely to receive chemotherapy (P = 0.03), and intermediate-risk pattern was not associated with chemotherapy use (P = 0.11). Women who received systemic chemotherapy had disease-free survival (5-year rate, 88.1% versus 90.2%, adjusted-hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.52-1.83, P = 0.94) and cause-specific survival (95.4% versus 94.8%, adjusted-HR 0.85, 95% CI 0.34-2.07, P = 0.71) similar to those who received concurrent chemo-radiotherapy on multivariable analysis. Similar results were seen among 329 women with multiple intermediate-risk factors (5-year rates for disease-free survival, chemotherapy versus concurrent chemo-radiotherapy, 87.1% versus 90.2%, P = 0.86; and cause-specific survival 94.6% versus 93.4%, P = 0.82). Cumulative local-recurrence (P = 0.77) and distant-recurrence (P = 0.94) risks were similar across the adjuvant therapy types.Our study suggests that systemic chemotherapy may be an alternative treatment choice for adjuvant therapy in intermediate-risk stage IB cervical cancer.
Project description:OBJECTIVE:To examine clinico-pathological factors associated with surgical complications and postoperative therapy for clinical stage IB-IIB cervical cancer. METHODS:This nationwide multicenter retrospective study examined women with clinical stage IB-IIB cervical cancer who underwent radical hysterectomy plus pelvic and/or para-aortic lymphadenectomy between 2008-2009 at 87 institutions of the Japanese Gynecologic Oncology Group (n = 693). Multivariate models were used to identify independent predictors of perioperative grade 3-4 complications and bladder dysfunction. RESULTS:The overall intraoperative and postoperative complication rates were 3.3% and 9.8%, respectively. Clinical stage was not associated with perioperative complications (P = 0.15). Radiotherapy-based adjuvant therapy was significantly associated with an increased risk of postoperative complications (radiotherapy alone: adjusted-odds ratio [OR] 3.19, 95% confidence interval [CI] 1.46-6.99, P = 0.004; radiotherapy plus chemotherapy: adjusted-OR 3.26, 95%CI 1.66-6.41, P = 0.001), whereas chemotherapy was not (P = 0.45). Nerve-sparing surgery significantly reduced the risk of postoperative bladder dysfunction (adjusted-OR 0.57, 95%CI 0.37-0.90, P = 0.02) whereas adjuvant chemotherapy increased the risk of bladder dysfunction (adjusted-OR 2.06, 95%CI 1.16-3.67, P = 0.01). Among women receiving adjuvant chemotherapy, nerve-sparing radical hysterectomy significantly reduced the risk of bladder dysfunction (15.0% versus 32.9%, OR 0.31, 95%CI 0.14-0.68, P = 0.004). After propensity score matching, survival outcomes were similar with both types of adjuvant therapy (radiotherapy-based versus chemotherapy, P>0.05). CONCLUSION:Our study highlighted two distinct complication profiles of adjuvant therapy after radical hysterectomy for clinical stage IB-IIB cervical cancer, with radiotherapy increasing grade 3-4 adverse events and chemotherapy increasing bladder dysfunction. In this setting, nerve-sparing surgery may be useful if chemotherapy is being considered for adjuvant therapy.
Project description:To determine the significance of depth and extent of lymphovascular space invasion (LVSI) on lymph node metastasis and recurrence in endometrial cancer.A case-control study was conducted to examine LVSI-positive (n?=?70) and LVSI-negative (n?=?641) stage I-III endometrial cancer cases that underwent hysterectomy-based surgical staging. The risk of lymph node metastasis and distant recurrence was estimated based on LVSI patterns.In multivariate analysis, deep (>50% invasion), and extensive (?7 foci/slide) LVSI patterns had a significantly increased risk of lymph node metastasis (incidence 57.6% and 72.7%, odds ratio 33.8 and 49.9, respectively, P?<?0.001) as compared to other traditional uterine factors (>50% myometrial tumor invasion, cervical stromal invasion, and adnexal involvement: incidence range 30.4-37.9%, odds ratio range 3.80-7.03). Deep and extensive of LVSI patterns were both significantly correlated to distant recurrence (P?<?0.001). Among women who received postoperative chemotherapy, deep and extensive LVSI patterns did not have increased risks for distant recurrence compared to no LVSI (P?=?0.47 and 0.32, respectively). Among women who received postoperative radiotherapy, the depth of LVSI was significantly associated with recurrence outside the radiated field (P?=?0.02).Depth and extent of LVSI are important predictors for lymph node metastasis and distant recurrence in endometrial cancer.
Project description:BACKGROUND: In this study, we sought to identify a criterion for the intermediate-risk grouping of patients with cervical cancer who exhibit any intermediate-risk factor after radical hysterectomy. METHODS: In total, 2158 patients with pathologically proven stage IB-IIA cervical cancer with any intermediate-risk factor after radical hysterectomy were randomly assigned to two groups, a development group and a validation group, at a ratio of 3 : 1 (1620 patients:538 patients). To predict recurrence, multivariate models were developed using the development group. The ability of the models to discriminate between groups was validated using the log-rank test and receiver operating characteristic (ROC) analysis. RESULTS: Four factors (histology, tumour size, deep stromal invasion (DSI), and lymphovascular space involvement (LVSI)) were significantly associated with disease recurrence and included in the models. Among the nine possible combinations of the four variables, models consisting of any two of the four intermediate-risk factors (tumour size ≥3 cm, DSI of the outer third of the cervix, LVSI, and adenocarcinoma or adenosquamous carcinoma histology) demonstrated the best performance for predicting recurrence. CONCLUSION: This study identified a 'four-factor model' in which the presence of any two factors may be useful for predicting recurrence in patients with cervical cancer treated with radical hysterectomy.
Project description:OBJECTIVE:To compare the survival outcomes of adjuvant radiotherapy and chemotherapy in women with uterine-confined endometrial cancer with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CCC). METHODS:Medical records of 80 women who underwent surgical staging for endometrial cancer were retrospectively reviewed. Stage I UPSC and CCC were pathologically confirmed after surgery. Survival outcomes were compared between the adjuvant radiotherapy and chemotherapy groups. RESULTS:Fifty-four (67.5%) and 26 (32.5%) women had UPSC and CCC, respectively. Adjuvant therapy was administered to 59/80 (73.8%) women (25 radiotherapy and 34 chemotherapy). High preoperative serum cancer antigen-125 level (25.1±20.2 vs. 11.5±6.5 IU/mL, p<0.001), open surgery (71.2% vs. 28.6%, p=0.001), myometrial invasion (MI) ≥1/2 (33.9% vs. 0, p=0.002), and lymphovascular space invasion (LVSI; 28.8% vs. 4.8%, p=0.023) were frequent in women who received adjuvant therapy compared to those who did not. However, the histologic type, MI ≥1/2, and LVSI did not differ between women who received adjuvant radiotherapy and those who received chemotherapy. The 5-year progression-free survival (78.9% vs. 80.1%, p>0.999) and overall survival (77.5% vs. 87.8%, p=0.373) rates were similar between the groups. Neither radiotherapy (hazard ratio [HR]=1.810; 95% confidence interval [CI]=0.297-11.027; p=0.520) nor chemotherapy (HR=1.638; 95% CI=0.288-9.321; p=0.578) after surgery was independently associated with disease recurrence. CONCLUSION:Our findings showed similar survival outcomes for adjuvant radiotherapy and chemotherapy in stage I UPSC and CCC of the endometrium. Further large study with analysis stratified by MI or LVSI is required.
Project description:OBJECTIVE:To evaluate the effect of lymph-vascular space invasion (LVSI) on location of recurrences in Danish patients with endometrial cancer. METHODS:This national cohort study (2005-2012) included 4,380 radically operated patients (no visual tumor, all distant metastasis removed). LVSI status was recorded in 3,377 (77.1%). In stage I patients, 2.6% received adjuvant radiotherapy and 1.4% adjuvant chemotherapy. Adjusted Cox regression was used to compare actuarial recurrence rates. RESULTS:LVSI was present in 18.7% of 3,377 patients with known LVSI status. Of these, 7.6% stage I patients with LVSI experienced an isolated locoregional and 19.4% a non-locoregional recurrence. Compared to no LVSI, 5-year recurrence rate was higher (25.5% vs. 8.5%) in patients with LVSI and the frequency of distant recurrences was strikingly higher (stage I: 15.2% vs. 2.7%), the effect being similar across International Federation of Gynecology and Obstetrics stages and histological types. In intermediate-risk stage I patients with LVSI, 8.0% experienced an isolated locoregional recurrence compared to 20.1% with non-locoregional recurrence, giving these patients a seriously adverse risk of survival. A separate analysis in patients with recurrences demonstrated that those with LVSI had significantly more distant recurrences (55.4% vs. 29.9%) and fewer isolated vaginal recurrences (24.3% vs. 42.8%) than patients with no LVSI. CONCLUSION:LVSI is a strong independent risk factor for the development of non-locoregional recurrences even in intermediate-risk stage I endometrial cancer. The non-locoregional recurrence pattern suggests a future focus for optimization of postoperative treatment in these patients.
Project description:The metastasis of cervical carcinoma is associated with the lymphovascular spread. The primary objective of the present study was to determine the prognostic value of lymphovascular space invasion (LVSI) in patients with early-stage cervical cancer in Jilin, China.In this retrospective cohort study, patients with early-stage cervical cancer (stage IB-IIA) at the Second Hospital of Jilin University from February 2014 to December 2016 were included in the analysis. All included participants underwent radical hysterectomy with pelvic lymphadenectomy. LVSI was identified by hematoxylin and eosin (H&E) staining. The primary outcomes are overall survival (OS) and progression-free survival (PFS). Kaplan-Meier curves were used to calculate the patient's survival. Survival was compared using the log-rank test, while risk factors for the prognosis were assessed by Cox regression analysis.The incidence of LVSI was positively associated with the depth of stromal invasion (P?=?.009) and lymph node metastasis (LNM, P?<?.001). LVSI is an independent factor that affects OS (P?=?.009) and PFS (P?=?.006) in patients with early stage cervical cancer. LNM status is an independent factor that affects postoperative OS (P?=?.005).The incidence of lymphatic vessel infiltration is positively associated with the depth of stromal invasion and LNM. LVSI is an independent risk factor for the prognosis of early cervical cancer. The results suggest that further large-scale studies are needed to improve the treatment for patients with LVSI.
Project description:OBJECTIVES:There is no consensus on whether giving adjuvant concurrent chemoradiotherapy (CCRT) is more effective than adjuvant radiotherapy (RT) alone in patients with early stage cervical cancer and intermediate-risk factor(s). The purpose of this study was to evaluate survival difference according to adjuvant treatment in the intermediate-risk group. METHODS:From 2000 to 2014, the medical records of patients with stage IB-IIA cervical cancer and a history of radical hysterectomy with pelvic lymph node dissection, followed by pelvic RT at a dose ?40 Gy were retrospectively reviewed. Among these, 316 patients with one or more intermediate-risk factor(s) and no high-risk factors were included. The criteria defined the intermediate-risk group as those patients with any of the following intermediate-risk factors: lymphovascular space involvement, over one-half stromal invasion, or tumor size ?4 cm. RESULTS:The median follow-up duration was 70 months (range: 3-203 months). According to adjuvant treatment (adjuvant RT alone vs. adjuvant CCRT), the 5-year recurrence-free survival rates (90.8% vs. 88.9%, p=0.631) and 5-year overall survival rates (95.9% vs. 91.0%, p=0.287) did not show a significant difference in patients with any of the intermediate-risk factors. In multivariate analysis, a distinct survival difference according to adjuvant treatment was not found regardless of the number of risk factors. CONCLUSION:The present study showed that giving RT together with chemotherapy is not more effective than RT alone for stage IB-IIA cervical cancer patients with intermediate-risk factor(s). TRIAL REGISTRATION:ClinicalTrials.gov Identifier: NCT01101451.
Project description:OBJECTIVES:To assess the survival of patients with cervical cancer (CC). Since the recommendations concerning cervical cancer management adopted by Polish medical societies do not differ significantly from the ESGO or non-European guidelines, and the fact that evaluation of the system for CC treatment in Poland, as well as the mortality rate of Polish women with CC, which is 70% higher than the average for European Union (EU) countries, justifies the hypothesis that treatment of CC in Poland deviates from the Polish and international recommendations. This article puts forward the current management of cervical cancer in Poland and discusses it in the context of ASCO guidelines. MATERIAL AND METHODS:A survey retrospective multicenter analysis of the medical records of 1247 patients with cervical cancer who underwent treatment for disease and who had completed at least two years of follow-up. RESULTS:Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower. CONCLUSION:Within the IA to II A cervical cancer patients studied group, the methods of treatment remained in line with ASCO guidelines for countries with the highest standard of care. Although concurrent radiotherapy and chemotherapy is a standard treatment of FIGO IB to IVA cervical cancer patients in enhanced- and maximum-resources settings, in our analysis, we found that the percentage of women subjected to chemotherapy was lower than in countries where total survival rates were lower. Our findings, together with the inconsistencies within the cervical cancer screening program, may be one of the explanations of poorer survival rate of women with cervical cancer in Poland.
Project description:This was a nation-wide retrospective study in Japan examining women who underwent radical hysterectomy for clinical stage IB-IIB cervical cancer with pelvic and/or para-aortic lymph node metastasis between 2004 and 2008. Time to recurrence or death and patterns of disease recurrence were compared based upon the adjuvant treatment pattern: whole pelvic radiotherapy alone (n?=?253), concurrent chemoradiotherapy (CCRT, n?=?502) and chemotherapy alone (n?=?319). Women who received chemotherapy alone had similar recurrence (5-year rates, 36.6% vs. 34.1%, adjusted-hazard ratio [HR] 0.95, 95% confidence interval [CI] 0.70-1.28, P?=?0.72) and cervical cancer mortality (24.7% vs. 21.8%, adjusted-HR 0.96, 95% CI 0.67-1.38, P?=?0.83) rates compared to those who received CCRT on multivariate analysis. However, when recurrence patterns were stratified, chemotherapy treatment was independently associated with decreased risk of distant recurrence (5-year cumulative rates, 19.2% vs. 24.6%, adjusted-HR 0.47, 95% CI 0.31-0.71, P?<?0.001) but increased risk of local recurrence (23.9% vs. 14.3%, adjusted-HR 2.03, 95% CI 1.34-3.08, P?=?0.001) compared to CCRT. Non-squamous histology, parametrial involvement and high lymph node ratio were independent predictors for local recurrence, and presence of multiple risk factors was associated with high 5-year cumulative local recurrence rate in the chemotherapy group: no risk factor 3.9%, single factor 14.2-22.1%, and multiple risk factors 27.8-71.9% (P?<?0.001). In conclusion, while exhibiting different recurrence patterns, systemic chemotherapy may be as effective a postoperative treatment as radiation-based therapy in node-positive high-risk stage IB-IIB cervical cancer. When tumor exhibits certain risk factors, chemotherapy alone is likely insufficient for local control and adding pelvic irradiation to systemic chemotherapy is recommended in this subgroup.
Project description:OBJECTIVES:Emerging evidence suggests that extent of lymphovascular space invasion (LVSI) predicts for risk of lymph node metastasis in endometrioid uterine cancers. However, this correlation remains unknown in the setting of uterine serous carcinoma (USC). We sought to examine the association between extent of LVSI and other histopathologic characteristics with risk of nodal metastasis for women with USC. MATERIALS/METHODS:Pathological data from all cases of uterine serous carcinoma between July 1998 to July 2015 at our institution were reviewed. Descriptive, univariate, and multivariate logistic regression analysis of selected pathologic features were performed. RESULTS:88 patients with USC underwent total abdominal or laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and selective lymphadenectomy. Surgical staging revealed the following FIGO stage distributions: I (41%), II (8%), III (32%), IV (19%). LVSI was present in 44 (50%) patients. 36 patients (41%) had LN metastases with median number of total nodes removed of 17 (range, 1-49). On univariate analysis, depth of myometrial invasion, LVSI, tumor size, and cervical stromal involvement were significantly associated with nodal involvement. In a multivariate model, LVSI (OR 6.25, 95% CI 2.2-18.0, p<0.01) and cervical stromal involvement (OR 3.33, 95% CI 1.10-10.0, p=0.03) were the only factors that remained significant. Among patients with LVSI-positive disease, extensive LVSI was associated with increased risk of nodal involvement compared to focal LVSI (90% vs 29%, p=0.04). CONCLUSIONS:Presence and extent of LVSI, and cervical stromal invasion are important predictors for lymph node metastasis in uterine serous carcinoma.