The management of inoperable Stage I endometrial cancer using intracavitary brachytherapy alone: A 20-year institutional review

doi:10.1016/j.brachy.2008.11.006

Brachytherapy

Volume 8, Issue 3, July–September 2009, Pages 278-283

https://doi.org/10.1016/j.brachy.2008.11.006 Get rights and content

Abstract

Objective

To review our institution's results with primary low dose rate (LDR) intracavitary brachytherapy using Heyman's capsules for medically inoperable cancer of the endometrium.

Methods

The study was a retrospective review of inoperable early-stage endometrial cancer patients at the Cross Cancer Institute in Edmonton, Canada, treated with primary radiotherapy from January 10, 1986 to July 17, 2006. Forty-four patients with International Federation of Gynaecology and Obstetrics (FIGO) clinical Stage I disease were included in the study. Kaplan–Meier survival analysis was performed to obtain estimates of overall survival (OS), disease-free survival, and disease-specific survival (DSS). Tumor grade was assessed as a potential predictor of OS by comparing survival curves using a log-rank test.

Results

The median OS time was 75.5 months (95% confidence interval 55.6–95.3 months). For the entire group, the 5- and 10-year OS was 60.5% and 24.0%, respectively. The 5- and 10-year DSS was 87.7% and 79.7%, respectively. For a subset treated as planned, the 5- and 10-year OS was 54.5% and 34.5%, respectively. The 5- and 10-year DSS was 83.0% and 76.4%, respectively. When stratified by grade, trends in survival analysis are inversely related to grade. Both the trend analysis and the log-rank test were statistically significant at a p < 0.05 level.

Conclusions

Our experience with LDR brachytherapy for the treatment of Stage I endometrial cancer is comparable to surgical treatment and to results reported in the literature for high dose rate brachytherapy. Further study that would help define the indications for a primary radiotherapeutic approach in early-stage endometrial cancer may lower current thresholds for recommending primary radiotherapy versus surgery.

Introduction

Endometrial cancer refers to cancer originating from the internal lining of the body of the uterus. Worldwide, the incidence of endometrial cancer in 2002 was 199,000 or 3.9% of cancers in women (1). The highest incidences are in North America (22.0 per 100,000) and Europe (11.8–12.5 per 100,000). Rates are low in southern and eastern Asia and most of Africa (less than 3.5 per 100,000). In the United States, it is the most common gynecologic cancer, representing 6% of all female cancers in 2005 (2).

Fortunately, most women present with potentially curable disease. Mortality worldwide in 2002 was estimated to be 50,000 or 1.7% of cancer deaths in women (1). The American Cancer Society has estimated that in the United States in 2006, there will be 41,200 new cases and 7,350 new cancer deaths because of endometrial cancer. It is a cancer of postmenopausal women; worldwide, 91% of cases occur in women 50 years and older (1).

Endometrial carcinoma is usually treated and staged surgically according to the criteria established in 1988 by the International Federation of Gynaecology and Obstetrics (FIGO). Surgical treatment consists of total abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node sampling, and peritoneal fluid cytologic evaluation. Most surgically staged endometrial cancers present with Stage I disease (71%) (3). Before 1988, and currently in cases that cannot be staged surgically, FIGO clinical staging criteria (1971) have been used.

Approximately 1–3% of early-stage endometrial cancer patients are deemed inoperable because of factors such as advanced age, obesity, or other medical conditions (4). Early-stage patients considered to be at high surgical risk can be treated with radiotherapy alone as the primary modality of treatment [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20]. Radiotherapy techniques used have included various combinations of external beam radiotherapy (EBRT), high- or low-dose-rate (HDR or LDR) uterine intracavitary brachytherapy, and HDR or LDR vaginal intracavitary brachytherapy. Reported disease-specific survival (DSS) rates have been comparable to those of women undergoing hysterectomy.

Section snippets

Methods

For this study, we carried out a retrospective chart review of all inoperable early-stage endometrial cancer patients at the Cross Cancer Institute in Edmonton, Alberta treated with primary radiotherapy from January 10, 1986 to July 17, 2006. Patients were staged clinically with routine blood chemistries, clinical examination, a chest X-ray, and imaging of the abdomen and pelvis for some as well. Followup including morbidity assessment was carried out by a radiation oncologist or gynecologic

Results

Fifty patients were reviewed for the study. We excluded 6 patients with Stage II disease or greater. Four patients had Stage II disease. These patients were treated with a planned combination of EBRT and ICRT. A patient with Stage III disease was treated with EBRT and ICRT. A sixth patient was excluded because Stage IV disease was treated with a combination of chemotherapy, EBRT, and ICRT with a palliative intent. The 44 remaining patients included in the study were presumed to have Stage I

Discussion

While recognizing the limitations of our study in terms of its retrospective nature and sample size, studies published on primary radiotherapy for the treatment of endometrial cancer are sparse and varied. In our literature search using the PubMed database, we could find no contemporary study that addressed the efficacy of LDR brachytherapy alone in the primary management of early endometrial cancer. In 1985, Patanaphan et al. found an absolute 5-year survival rate of 56% and a determinate

Conclusion

Our institution's 20-year history with Ir192 LDR intracavitary brachytherapy using Heyman's capsules in the treatment of early-stage endometrial cancer for inoperable patients is comparable not only with previously reported results in the literature, but also with the gold standard of surgical management with or without adjuvant radiotherapy. Comparisons with other management approaches such as palliative EBRT or progestin therapy alone warrants further study. It is timely to remind ourselves

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Cited by (20)

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations, part II
2021, Gynecologic Oncology
Citation Excerpt :
Several studies evaluated patients in this unique circumstance. The five-year overall survival following primary radiation therapy ranges from 39 to 71% [78,79] but locoregional control and cancer-specific survival can be excellent with rates of 90% and 86% respectively in one study of 45 inoperable clinical stage I patients treated with high-dose rate image-guided brachytherapy [80,81] Imaging may be used to assess for extrauterine disease.
In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women.
This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.
Toxicity and outcomes associated with high-dose rate brachytherapy for medically inoperable endometrial cancer
2021, Brachytherapy
Citation Excerpt :
Therefore, it is essential that these women have effective, safe treatment alternatives. Multiple studies have shown that for these patients, radiotherapy in the form of BT with or without EBRT can be an effective modality (4, 6, 12–14). Studies have yielded 5-year disease-free survival (DFS) as high as 88% in patients treated with definitive radiation.
To evaluate toxicity in inoperable endometrial cancer (EC) treated with definitive radiation therapy (RT).
Patients treated with definitive RT for EC were retrospectively reviewed. EQD2 values were calculated for bladder, rectum, and sigmoid. Acute and late toxicities were retrospectively graded. Descriptive statistical analysis was performed.
Fifty-one patients were included. The majority of patients had endometrioid histology (N = 46, 90.2%) and Grade 1 disease (N = 32, 62.75%). Thirty-seven patients (72.5%) were treated with image-guided BT (IGBT) and 14 (27.5%) with two-dimensional BT. Forty patients (78.4%) received EBRT + BT and 11 (21.57%) received BT alone. No grade 2 (G2) or higher toxicities were reported with BT alone. G2 or higher acute toxicities with EBRT + BT were G2 proctitis (N = 2, 5.0%) and G3 proctitis (N = 1, 2.5%). Late toxicities included G3 vaginal stenosis (N = 1, 2.5%), proctitis (N = 1, 2.5%), enteritis (N = 1, 2.5%), and one G4 gastrointestinal bleed. One- and 2-year local control were 100% with BT alone and 93% and 89%, respectively, with EBRT + BT. One- and 2-year locoregional control were 100% with BT and 97% and 93%, respectively, with EBRT + BT. Recurrence-free survival was 89% at 1 and 2 years with BT alone compared to 87% and 80% with EBRT + BT. One- and 2-year overall survival were 88% and 72% with BT alone compared to 94% and 84% with EBRT + BT. There were no statistically significant differences in cancer control between the two groups.
Women with inoperable EC treated with definitive RT have low toxicity rates and durable local control.
Radiation and hormonal therapy for primary treatment of stage I endometrial cancer and long-term survival
2020, Gynecologic Oncology
Estimate the association between non-surgical management (NSM) (e.g. hormonal or radiation therapy) and overall survival among women with stage I endometrioid endometrial cancer (EEC) and identify patient and facility characteristics associated with receipt of NSM.
Women >45 years of age with clinical stage I EEC were identified in the National Cancer Database from 2004 to 2016. Women treated with NSM were compared with women treated initially with hysterectomy. Patient and facility characteristics associated with NSM were evaluated using logistic regression models. Association with overall survival was examined using log-rank tests, Kaplan-Meier curves, and Cox proportional hazards regression models with and without propensity score matching (PSM).
A total of 112,469 women underwent treatment for stage I EEC between 2004 and 2016. 2776 (3%) received NSM, of whom 1987 (71%) received radiation therapy, 688 (25%) received hormonal therapy, and 101 (4%) received both. Older age, black race, higher Charlson-Deyo scores, Medicaid insurance, and low annual facility hysterectomy volume were associated with receiving NSM. The 5-year survival rate was 40% (95%CI: 37%–42%) for women with NSM compared to 89% (95%CI: 88%–89%) for hysterectomy. Women treated with NSM died at a faster rate than those who underwent primary hysterectomy (HR 7.6, 95%CI: 7.2–8.0; p < 0.001). This statistically significant difference in survival persisted in adjusted Cox proportional hazards models and after PSM.
Women treated with NSM had a significantly higher risk of death compared to those undergoing hysterectomy for stage I EEC. Caution should be used when selecting patients for NSM given its worse outcomes.
Uterine Cancer
2019, Abeloff’s Clinical Oncology
Endometrial cancer is the most common gynecologic malignancy in the United States. Abnormal uterine bleeding is the most common presenting symptom for women diagnosed with endometrial cancer. Although genetic factors account for a small percentage of women with endometrial cancer, women with Lynch syndrome have a markedly increased risk for this disease. Lynch syndrome patients have mutations in DNA mismatch repair genes, creating alterations in microsatellite regions. Additionally, the Cancer Genome Atlas was analyzed and compelling evidence revealed that four categories of endometrial cancers exist. These four categories may confer different prognosis for patients with this malignancy. Due to the fact that most cancers are confined to uterus, surgery is a mainstay of treatment. The role of lymphadenectomy is debatable; however, the introduction of the sentinel lymph node technique has introduced a possible surgical alternative with reduced morbidity. Adjuvant therapy is not yet standardized and randomized trials are ongoing, which may help maximize treatment outcomes. Moreover, novel therapies are being introduced into the treatment of endometrial cancer in hopes of improving survival outcomes for women.
Endometrial cancer in an increasingly obese population: Exploring alternative options when surgery may not cut it
2018, Gynecologic Oncology Reports
Citation Excerpt :
As such, exploring alternative treatment options for this patient population is crucial, and radiation and hormonal therapy have often been utilized for non-surgical candidates. Several studies have investigated outcomes after radiation therapy alone in early endometrial cancer and it remains a viable option for local disease control in patients who cannot undergo surgery following an endometrial cancer diagnosis (SGO Clinical Practice Endometrial Cancer Working Group et al., 2014; Potish et al., 1985a; Varia et al., 1987a; Shenfield et al., 2009a). Hormonal therapy may be another treatment alternative for this particular group of patients.
The study objectives were to describe outcomes of obese patients with early endometrial cancer following primary non-surgical treatment, assess predictors of response, and estimate the increased surgical risk for these women.
Retrospective chart review identified women with early stage endometrial cancer at a single institution with BMI ≥ 30 kg/m² who did not undergo surgery as primary treatment modality due to obesity and medical co-morbidities. Clinicopathologic factors were abstracted, characteristics of responders vs. non-responders compared and the National Surgical Quality Improvement Program (NSQIP) surgical risk calculator utilized to quantify surgical risks.
Fifty-one patients were identified, with a mean BMI of 49.0 kg/m². The NSQIP calculator predicted a significantly higher complication rate for our cohort compared to the expected average risk for hysterectomy (18.8% vs 7.2%, p < .0001). The majority of patients were treated with radiation alone (49%), followed by hormone therapy (45.1%). Response rates were 38.1% for women treated with hormones and 63.6% in the radiation group (p = .063). No significant differences were identified between responders and non-responders with regard to NSQIP scores, BMI, co-morbidities or age. Among those with persistent or progressive disease, 87.5% responded to secondary treatment. Only one death was from cancer progression. Two individuals died following treatment complications (one surgical, one chemotherapy); the remaining twelve deaths were due to pre-existing co-morbidities.
Hormone and radiation therapy are both viable options for obese patients deemed to have too significant risk of surgical complications. Pursuing surgical intervention in this population may do more harm than good.
Management of elderly patients with early-stage medically inoperable endometrial cancer: Systematic review and National Cancer Database analysis
2017, Brachytherapy
To evaluate the effectiveness of radiation therapy among elderly patients who are deemed medically inoperable.
We searched PubMed to identify studies from the past 25 years that reported outcomes of medically inoperable endometrial cancer patients treated with radiation alone. The National Cancer Database (NCDB) was queried to identify patients 65 years and older with Stage I–II medically inoperable endometrial cancer. Univariable and multivariable models were performed to investigate the impact of prognostic factors on overall survival.
Thirteen papers met inclusion criteria for the systematic review. Overall survival for Stage I tumors at 5 years was 30–95%. Reported pelvic control for the 888 total patients with Stage I tumors was 80–100% and 61–89% for Stage II. Late complications for all patients treated ranged from 0% to 21% across patients. The NCDB analysis demonstrated that any radiotherapy was associated with improved survival over no local therapy. Combination therapy (external beam radiation therapy + brachytherapy) was associated with the most favorable survival with a hazard ratio (HR) of 0.442 (p < 0.001 over no radiotherapy), although benefits were also seen with external beam radiation therapy alone (HR 0.694, p < 0.001) and with brachytherapy alone (HR 0.499, p < 0.001) compared to no radiotherapy.
The available evidence suggests high rates of local control after radiation therapy for elderly women with Stage I–II medically inoperable endometrial cancer. Our analysis of the NCDB suggests that radiation therapy improves survival, and combination therapy provides the most favorable outcomes. Given a relatively favorable toxicity profile, definitive radiation therapy should be considered a preferred approach for patients with medically inoperable endometrial cancer.

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Point/CounterpointThe management of inoperable Stage I endometrial cancer using intracavitary brachytherapy alone: A 20-year institutional review

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Int J Gynaecol Obstet

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Gynecol Oncol

Point/Counterpoint
The management of inoperable Stage I endometrial cancer using intracavitary brachytherapy alone: A 20-year institutional review