Radiotherapy in the adjuvant setting of cervical carcinoma: treatment, results, and prognostic factors (original) (raw)
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International Journal of Gynecological Cancer, 2022
Background The role of adjuvant treatment in the intermediate-risk group of patients with early-stage cervical cancer is controversial and is supported by a single randomized Gynecologic Oncology Group (GOG) 92 study performed more than 20 years ago. Recent retrospective studies have shown excellent local control in this group of patients after radical surgery with no additional adjuvant treatment. Primary Objective To evaluate if adjuvant (chemo) radiation is associated with a survival benefit after radical surgery in patients with intermediate-risk cervical cancer. Study Hypothesis Radical surgery alone is non-inferior to the combined treatment of radical surgery followed by adjuvant (chemo)radiation in disease-free survival in patients with intermediate-risk cervical cancer. Trial Design This is a phase III, international, multicenter, randomized, non-inferiority trial in which patients with intermediate-risk cervical cancer will be randomized 1:1 into arm A, with no additional treatment after radical surgery, and arm B, receiving adjuvant external beam radiotherapy±brachytherapy ± concomitant chemotherapy. Patient data will be collected over 3 years post-randomization of the last enrolled patient for primary endpoint analysis or for 6 years for the overall survival analysis. Major Inclusion/Exclusion Criteria Patients with intermediate-risk early-stage cervical cancer (IB1-IIA), defined as lymph node-negative patients with a combination of negative prognostic factors (tumor size >4 cm; tumor size >2 cm and lymphovascular space invasion; deep stromal invasion >2/3; or tumor-free distance <3 mm) with squamous cell carcinoma or human papillomavirus (HPV)-related adenocarcinoma, are eligible for the trial. Primary Endpoint Disease-free survival defined as time from randomization to recurrence diagnosis. Sample Size 514 patients from up to 90 sites will be randomized. Estimated Dates for Completing Accrual and Presenting Results It is estimated that the accrual will be completed by 2027 (with 3 additional years of follow-up) and primary endpoint results will be published by 2031. Estimated trial completion is by 2034. Trial Registration NCT04989647.
Annals of Surgical Oncology, 2015
Background. The aim of this study was to identify clinical variables that may predict the need for adjuvant radiotherapy after neoadjuvant chemotherapy (NACT) and radical surgery in locally advanced cervical cancer patients. Methods. A retrospective series of cervical cancer patients with International Federation of Gynecology and Obstetrics (FIGO) stages IB2-IIB treated with NACT followed by radical surgery was analyzed. Clinical predictors of persistence of intermediate-and/or high-risk factors at final pathological analysis were investigated. Statistical analysis was performed using univariate and multivariate analysis and using a model based on artificial intelligence known as artificial neuronal network (ANN) analysis. Results. Overall, 101 patients were available for the analyses. Fifty-two (51 %) patients were considered at high risk secondary to parametrial, resection margin and/or lymph node involvement. When disease was confined to the cervix, four (4 %) patients were considered at intermediate risk. At univariate analysis, FIGO grade 3, stage IIB disease at diagnosis and the presence of enlarged nodes before NACT predicted the presence of intermediate-and/ or high-risk factors at final pathological analysis. At multivariate analysis, only FIGO grade 3 and tumor diameter maintained statistical significance. The specificity of ANN models in evaluating predictive variables was slightly superior to conventional multivariable models. Conclusions. FIGO grade, stage, tumor diameter, and histology are associated with persistence of pathological intermediate-and/or high-risk factors after NACT and radical surgery. This information is useful in counseling patients at the time of treatment planning with regard to the probability of being subjected to pelvic radiotherapy after completion of the initially planned treatment.
Radiotherapy and Oncology, 1999
Background and purpose: The aim of this study was to assess the results of treatment (surgery alone or surgery and postoperative radiotherapy) for early-stage cervical carcinoma and to determine the morbidity associated with adjuvant radiotherapy. A subset of these patients (n 10) was irradiated postoperatively for tumor related negative prognostic factors only and this retrospective analysis was also performed to determine if this decision was right and if the selection for this treatment was based on the right criteria.
Current Oncology
The standard of care for early-stage cervix cancer is radical hysterectomy with pelvic lymphadenectomy. Adjuvant radiotherapy (RT) or chemoradiotherapy may be administered to reduce the risk of recurrence in patients considered to be at elevated risk based on a combination of pathologic factors. We performed a retrospective review to determine oncologic outcomes in patients treated for early-stage cervix cancer and to determine if surgical approach impacted oncologic outcomes or the decision to use adjuvant therapy. In total, 174 women underwent radical hysterectomy and pelvic lymphadenectomy over the 15-year period. Most of these women (146) had open surgery and 28 had minimally invasive surgery (MIS). In total, 81 had adjuvant pelvic RT; 76 in the open surgery group (52%) and 5 in the MIS group (18%). Five-year PFS and OS, respectively, were 84% and 91%. Five-year PFS was significantly lower in patients who had MIS vs. open surgery, without a difference in 5-year OS, suggesting MI...
Molecular and Clinical Oncology, 2013
The efficacy of radiotherapy (RT) for adenocarcinoma (AC) is controversial, although patients with AC of the uterine cervix are treated in a similar manner to those with squamous cell carcinoma (SCC). This retrospective study was conducted to evaluate the efficacy of adjuvant RT for patients with AC compared to those with SCC following radical hysterectomy. A total of 820 patients with stage IB-IIB cervical cancer, who underwent type III radical hysterectomy between 1997 and 2003, were retrospectively examined; the sample included 280 patients with AC and 540 with SCC. A total of 139 patients with AC and 327 with SCC underwent adjuvant treatment. The histological type did not affect the outcome for patients with stage I disease; however, stage II patients with AC exhibited a significantly worse 5-year overall survival (OS) rate compared to those with SCC. Patients with SCC exhibited significantly higher lymph node involvement compared to those with AC in stage IB1; however, there were no differences between stages IB2 and II. Among patients with lymph node involvement, patients with AC exhibited a significantly worse 5-year survival rate compared to those with SCC (46.4 vs. 72.3%, respectively; P=0.0005). Among patients receiving adjuvant RT, those with AC recurred more frequently compared to those with SCC, particularly in the pelvic cavity, including the vaginal stump and̸or pelvis (24.6 vs. 10.5%, respectively; P= 0.0022). By contrast, the histological type did not affect the incidence of recurrence in paraaortic lymph nodes and̸or distant recurrence. In conclusion, RT may not suffice as an adjuvant treatment for patients with cervical AC following radical hysterectomy.
International Journal of Gynecological Cancer, 1991
This paper addresses evolving concepts in the definition and management of patients with invasive cervical cancer Stages IB and HA who are at increased risk for recurrence after radical hysterectomy and pelvic lymphadenectomy. The discussion will be restricted to the more common histological types, squamous and adenocarcinomas, and their variants. It is suggested that outcome is determined both by lymph node metastases and by certain attributes of the primary tumor. There is evidence that the anatomic sites of relapse for tumor-associa ted and nodal-associated risk factors may be dissimilar, which suggests different therapeutic approaches and opportunities for improving outcome.
American Journal of Obstetrics and Gynecology, 2009
Prognostic factors in early cervical cancer have been debated for many years and have been used as an indication for postradical hysterectomy radiation therapy. A recent Gynecologic Oncology Group protocol suggested that large lesions, deep invasion, or capillary-like space had better recurrence-free survival, but not overall survival, if postoperative radiation was given. When the published data were evaluated, the authors' conclusions were questioned. The choice of prognostic factors does not seem appropriate based on the data that were presented.
Post-operative radiotherapy in patients with early stage cervical cancer
Gynecologic Oncology, 2014
The aim of this study is to investigate the impact of treatment policy changes in cervical cancer patients treated with adjuvant (chemo) radiotherapy. Between 1970 and 2007, 292 patients received adjuvant radiotherapy after a radical hysterectomy with pelvic lymphadenectomy for early stage cervical carcinoma. All patients received pelvic radiotherapy (40 Gy-46 Gy in 1.8 Gy-2 Gy/fraction). Vaginal vault brachytherapy boost (10-14 Gy) was increasingly used for patients with high-risk factors, and since 1993 systematically applied in patients with at least 2 of the 3 risk factors: adenocarcinoma, nodal involvement and parametrial invasion. Cisplatin-based chemotherapy was introduced in this group of patients from 2000. The 5-year cumulative risk of local recurrence (CRLR) was 13% (95%CI 9%-17%), resulting in an overall 5-year survival (OS) of 78% (95%CI 83%-73%). Since 1970, the OR for the 5-year locoregional recurrence risk (LRR) decreased from 2.5 to 1.15 (linear-OR=-0.02/year). The OR for the 5-year mortality risk reduced from 2.2 in 1970 to 1.0 in 2007 (linear-OR=-0.03/year). The largest risk reductions were observed before 1990 with a minor rise after 2002. The risk of severe late toxicity reduced from 1.8% to 1.5% (linear-OR=-0.03/year). The addition of concomitant adjuvant chemotherapy since 2000 may have benefited a subgroup of patients with squamous cell carcinoma, but not the patients with adenocarcinoma, and after introduction of chemotherapy the risk of severe late toxicity tripled from 2% to 7%. Since 1970, tumour recurrence risk and mortality have decreased, as radiation dose increased. The potential benefit of concomitant adjuvant chemotherapy could not be demonstrated in this nonrandomized study.
Purpose: To investigate, in a phase III randomized trial, whether postoperative external-beam irradiation to the standard pelvic field improves the recurrence-free interval and overall survival (OS) in women with Stage IB cervical cancers with negative lymph nodes and certain poor prognostic features treated by radical hysterectomy and pelvic lymphadenectomy. Methods and Materials: Eligible patients had Stage IB cervical cancer with negative lymph nodes but with 2 or more of the following features: more than one third (deep) stromal invasion, capillary lymphatic space involvement, and tumor diameter of 4 cm or more. The study group included 277 patients: 137 randomized to pelvic irradiation (RT) and 140 randomized to observation OBS). The planned pelvic dose was from 46 Gy in 23 fractions to 50.4 Gy in 28 fractions. Results: Of the 67 recurrences, 24 were in the RT arm and 43 were in the OBS arm. The RT arm showed a statistically significant (46%) reduction in risk of recurrence (hazard ratio [HR] ؍ 0.54, 90% confidence interval [CI] ؍ 0.35 to 0.81, p ؍ 0.007) and a statistically significant reduction in risk of progression or death (HR ؍ 0.58, 90% CI ؍ 0.40 to 0.85, p ؍ 0.009). With RT, 8.8% of patients (3 of 34) with adenosquamous or adenocarcinoma tumors recurred vs. 44.0% (11 of 25) in OBS. Fewer recurrences were seen with RT in patients with adenocarcinoma or adenosquamous histologies relative to others (HR for RT by histology interaction ؍ 0.23, 90% CI ؍ 0.07 to 0.74, p ؍ 0.019). After an extensive follow-up period, 67 deaths have occurred: 27 RT patients and 40 OBS patients. The improvement in overall survival (HR ؍ 0.70, 90% CI ؍ 0.45 to 1.05, p ؍ 0.074) with RT did not reach statistical significance. Conclusions: Pelvic radiotherapy after radical surgery significantly reduces the risk of recurrence and prolongs progression-free survival in women with Stage IB cervical cancer. RT appears to be particularly beneficial for patients with adenocarcinoma or adenosquamous histologies. Circumstances that may have influenced the overall survival differences are considered. © 2006 Elsevier Inc. Stage IB cervical cancers, Postoperative pelvic irradiation, Prognostic factors.