Clinical behavior of 203 stage II endometrial cancer cases: The impact of primary surgical approach and of adjuvant radiation therapy

Abstract. Sartori E, Gadducci A, Landoni F, Lissoni A, Maggino T, Zola P, Zanagnolo V. Clinical behavior of 203 stage II endometrial cancer cases: The impact of primary surgical approach and of adjuvant radiation therapy.
The aim of this study was to verify the impact of primary surgical approach and adjuvant radiation therapy (RT) on survival, recurrence rate, and pattern of relapse in stage II endometrial cancer patients. Two hundred three subjects were retrospectively reviewed; 135 (66%) underwent simple hysterectomy (SH) and 68 (34%) radical hysterectomy (RH). Sixty-six of 111 (59%) of stage IIA and 67 of 92 (73%) of stage IIB patients underwent adjuvant radiation therapy. Actuarial survival rates for stage IIA and IIB were 86% and 74% at 5 years and 82% and 68% at 10 years, respectively. Survival rates by surgical procedure were 79% in the SH group and 94% in the RH group at 5 years and 74% and 94% at 10 years, respectively ( P < 0.05). The overall recurrence rate was 13.8% (28/203); by adjuvant treatment it was 18.6% (13/70) in the observation group and 11.3% (15/133) in the RT group. Most of the relapses were locoregional in the observation group and distant in the RT group. Survival rates by RT were not statistically different. Subjects treated with RH improved their survival compared with the SH group; the difference was significant, but randomized studies should confirm this trend. Although adjuvant RT seemed to reduce the recurrence rate, there was no significant difference in survival, and so the role of RT still needs further verification.     

Salvage of isolated vaginal recurrences in women with surgical stage I endometrial cancer: a multiinstitutional experience

The objective of this study was to evaluate the treatment outcomes and risk factors of women with surgical stage I endometrial adenocarcinoma who were initially treated with surgery alone and subsequently developed isolated vaginal recurrences. Patients with surgical stage I endometrial adenocarcinoma diagnosed from 1975 to 2002 were identified from tumor registry databases at seven institutions. All patients were treated with surgery alone including a total hysterectomy, bilateral salpingo-oophorectomy, pelvic (+/- para-aortic) lymph node dissection, and peritoneal cytology and did not receive postoperative radiation therapy. Vaginal recurrences were documented histologically. Metastatic disease in the chest and abdomen was excluded by radiologic studies. Overall survival was calculated by the Kaplan-Meier method. Sixty-nine women with surgical stage I endometrial cancer with isolated vaginal recurrences were identified. Of the 69 patients, 10 (15%) were diagnosed with stage IA disease, 43 (62%) were diagnosed with stage IB disease, and 16 (23%) were diagnosed with stage IC disease. Patients diagnosed with grade 1 disease were 22 (32%), grade 2 disease were 26 (38%), and grade 3 disease were 21 (30%). Among women, 81% with isolated vaginal recurrences were salvaged with radiation therapy. The mean time to recurrence was 24 months, and the mean follow-up was 63 months. Among women, 18% died from subsequent recurrent disease. The 5-year overall survival was 75%. The majority of isolated vaginal recurrences in women with surgical stage I endometrial cancer can be successfully salvaged with radiation therapy, further questioning the role of adjuvant therapy for patients with uterine-confined endometrial cancer at the time of initial diagnosis.     

Radiation-associated endometrial cancers are prognostically unfavorable tumors: a clinicopathologic comparison with 527 sporadic endometrial cancers

INTRODUCTION: Previous reports have suggested that patients who have undergone pelvic radiation for cervical cancer are at risk for developing poorly differentiated endometrial cancers with poor prognoses. MATERIALS AND METHODS: We conducted a retrospective chart and histologic review of patients from Memorial Sloan-Kettering Cancer Center and MD Anderson Cancer Center diagnosed with endometrial cancer after radiation therapy (RT) for cervical cancer from 1976 to 2000. The comparison group comprised MSKCC endometrial cancer patients whose tumors were not radiation associated ("sporadic cancers"). RESULTS: We identified 23 patients who developed endometrial carcinoma or carcinomasarcoma after RT for cervical carcinoma and 527 sporadic endometrial cancer patients. When radiation-associated endometrial cancers (RAECs) were compared with sporadic cancers, significant differences were noted with regard to stage, grade and histologic subtype distribution. In the RAEC group, there were 16 (70%) stages III and IV cancers compared with 101 (19%) in the sporadic group (P<0.001). There were 20 (87%) grade 3 cancers in the RAEC group versus 161 (31%) in the sporadic group (P<0.001). There were 16 (70%) high-risk histologic subtypes (serous, clear cell, carcinosarcoma, undifferentiated) in the RAEC group versus 79 (15%) in the sporadic group (P<0.001). Median survival in the RAEC group was 24 months versus not reached in the sporadic group (P<0.001). Radiation remained a significant factor for poor prognosis in a stratified analysis, in which we compared sporadic and RAEC cancers controlled for age, histology, grade and stage. However, radiation lost significance in a multivariate analysis, in which stage- and grade-matched cancers from both groups were compared. DISCUSSION: The clinicopathologic characteristics of RAECs, which include a preponderance of high-stage, high-grade and high-risk histologic subtypes, indicate that these tumors differ from sporadic endometrial carcinomas. However, patients with RAECs do not appear to have a significantly worse prognosis when compared with patients with high-stage and high-grade sporadic cancers.     

Impact of tumor volume-directed involved field radiation therapy integrated in the management of recurrent ovarian cancer

OBJECTIVES: Assess the role of involved field radiation therapy (IFRT) in recurrent ovarian cancer. METHODS: Thirty-five patients with a diagnosis of epithelial ovarian cancer received radiation therapy at LUMC between 1991 and 2001. Of these, 20 received tumor volume-directed IFRT for localized extraperitoneal recurrences (either as consolidation following debulking surgery or as attempted salvage if unresectable) and form the basis of this report. All patients were heavily pretreated with multiple chemotherapy regimens. Eleven patients had optimal debulking of their recurrences prior to radiation. IFRT was primarily with external beam (median dose 50.4 Gy). Appropriate statistical analyses evaluated association among disease-free (DFS), overall survival (OS), local recurrence-free (LRFS), and various prognostic factors. LRFS was defined as freedom from in-field recurrences and was considered as a measure of effectiveness of radiotherapy. RESULTS: Of 20 patients, 17 had a complete response after RT. The actuarial LRFS, OS, and DFS at 5 years from date of radiation were 66%, 34%, and 34%, respectively. The LRFS at 3 years was 89% for those with optimal resection vs. 42% for those with gross residual/unresectable tumor, which was significantly better (P = 0.04). The corresponding 3-year DFS was 72% vs. 22% and 5-year OS was 50% vs. 19%, respectively. Acute complication of RT was mild, half had Grade 1-2 gastrointestinal (GI) toxicity, three patients had Grade 3-4 late GI effects. CONCLUSION: IFRT is effective in controlling localized recurrences of ovarian cancer, especially after they are optimally debulked (89% local control and 50% 5-year overall survival in this subgroup), and is relatively well tolerated in these heavily pretreated patients.     

Role of wide/radical hysterectomy and pelvic lymph node dissection in endometrial cancer with cervical involvement

OBJECTIVE: The goal of this work was to assess retrospectively the role of wide/radical hysterectomy (RH) and pelvic lymph node dissection (LND) in endometrial cancer with cervical involvement. METHODS; From 1984 to 1993, 82 patients with endometrial cancer and cervical involvement were surgically managed at our institution. Of 57 patients with stage II (59%) or III (41%) disease receiving no preoperative therapy, 22 (39%) had simple hysterectomy (SH) and 35 (61%) had RH. Forty-four patients (77%) had pelvic LND, and 38 (67%) had adjuvant radiotherapy (RT). Median follow-up was 70 months. RESULTS: The 5-year disease-related survival (DRS) and recurrence-free survival (RFS) were 73 and 63%, respectively. Five-year DRS and RFS were 68 and 50%, respectively, in the SH group compared with 76% (P = 0.1) and 71% (P = 0.04) in the RH group. Distant recurrences occurred in 45% of patients with SH and in 23% with RH (P = 0.08). Local recurrence rates did not differ significantly. Considering only stage II tumors, we did not observe any recurrence among patients with negative nodes who had RH, irrespective of the administration of adjuvant RT. By contrast, adjuvant RT improved local control (even if not significantly) in stage II patients who had SH. Five-year DRS of stage III patients was 47%, but it was improved by adjuvant RT in the subgroup of patients who had RH. Independent variables associated with prognosis were stage III disease, deep myometrial invasion, RH, and adjuvant RT. CONCLUSION: RH and adjuvant RT appear to improve prognosis in endometrial cancer with cervical involvement. In particular, radical surgery alone is therapeutic in stage II patients with negative nodes, irrespective of the administration of RT. By contrast, RT can possibly improve local control in stage II patients who previously had SH. Overall, stage III patients have a poor prognosis that can be improved by a combination of radical surgery and adjuvant RT; however, associated therapy directed to extrapelvic sites is probably needed in patients with extrauterine disease.     

Vaginal brachytherapy alone: an alternative to adjuvant whole pelvis radiation for early stage endometrial cancer

OBJECTIVE: Postoperative management of early stage adenocarcinoma of the endometrium remains controversial. The use of pelvic radiation therapy as shown by the Gynecologic Oncology Group (GOG)-99 trial improves the event free interval at the cost of increased toxicity. We reviewed and compared our results treating early stage endometrial adenocarcinoma using hypofractionated high dose rate (HDR) vaginal brachytherapy (VB) alone with the results of the GOG-99. METHODS: From 1992 to 2002, 243 endometrial cancer patients were treated with TAH/BSO and selective lymph node dissection followed by adjuvant radiotherapy (RT). Of these, 50 FIGO stage I-II (occult) adenocarcinoma (no clear cell or serous papillary) of the endometrium were managed with HDR hypofractionated VB as monotherapy using Iridium-192 to a dose of 30 Gy in 6 fractions twice weekly prescribed to a depth of 5 mm and median length of 4 cm. The characteristics, toxicity rates, and outcomes of our patients were compared with the results of the GOG-99. The median follow up of our patients and the GOG-99 were 3.2 years and 5.8 years, respectively. RESULTS: Patient characteristics including age, stage, and grade were similar in our study and the GOG-99. The local recurrence rate in our study, the pelvic RT arm of the GOG-99, and the no RT arm of the GOG-99 were 4% (n = 2), 2% (n = 3), and 9% (n = 18), respectively. In our study, one patient failed in the vagina alone and a second patient failed in the vagina and pelvis. In the GOG-99, the vagina as a component of locoregional failure was also the most common failure site in the no RT arm 77.8% (n = 14) and in the RT arm 100% (n = 3). The 2-year cumulative recurrence rate in our study was 2%, which compares favorably with the GOG-99 pelvic RT arm (3%) and observation arm (12%). Four-year survival rates of the no RT arm of the GOG-99, the RT arm of the GOG-99, and our study with HDR VB were 86%, 92%, and 97%, respectively. Chronic grade 2 toxicity rates were reduced by the use of VB compared to pelvic RT, especially GI toxicity 0% vs. 34% (P value < 0.001), and GI obstruction 0% vs. 7% (P value = 0.08). CONCLUSION: Stage I-II (occult) endometrial adenocarcinoma treated with postoperative HDR vaginal brachytherapy has similar overall survival, locoregional failure rates, and cumulative recurrence rates to standard fractionation external beam pelvic RT with the benefit of much lower toxicity rates and shorter overall treatment time.     

Pathologic stage III endometrial cancer treated with adjuvant radiation therapy

Gerszten K, Faul C, Huang Q. Pathologic stage III endometrial cancer treated with adjuvant radiation therapy. Int J Gynecol Cancer 1999; 9: 243–246.
This study was undertaken to evaluate the outcome of pathologic stage III endometrial carcinoma treated with adjuvant radiation therapy (RT). A retrospective review was performed on 32 patients receiving adjuvant RT following abdominal hysterectomy for stage III endometrial carcinoma (19 IIIA, 2 IIIB, 11 IIIC) between 1980 and 1996. Papillary-serous and clear cell adenocarcinomas were excluded. Pathologic nodal sampling was performed on 25 patients (78%). All patients received postoperative external beam RT to the pelvis and 25 of 32 received an additional brachytherapy boost to the vaginal apex. Three patients with involved para-aortic nodes received extended field RT. Mean follow up was 70 mos. Twenty-four patients remain disease-free at mean follow-up of 68 mos. Distant recurrence (DR) occurred in 7 patients at mean of 38 mo. Two local failures were associated with DR. Six patients died of disease after recurrence despite salvage systemic therapy. One patient developed isolated local failure (vaginal apex) and remains disease-free 37 mo after surgical/chemotherapeutic salvage. 5 of 8 (45%) stage IIIC patients developed recurrence vs. only 2 of 19 (10%) stage IIIA cases. 2 of 3 patients treated with extended field RT for positive para-aortic nodal disease remain disease-free at 128 and 56 mo. Long-term survival can be achieved in stage III endometrial carcinoma. Few patients with either adnexal metastases or positive cytology alone develop recurrence. However, patients with stage IIIC disease fare poorly with local therapy alone .     

Does Radical Hysterectomy for Clinically Apparent Stage II Endometrial Cancer Affect Risk of Local Recurrence?

ObjectiveCompare recurrence-free survival (RFS) and morbidity between radical hysterectomy (RH) and simple hysterectomy (SH) for clinically diagnosed stage II endometrial cancer.MethodsA multicentre, retrospective study, from 2000 to 2015, involving patients with endometrial cancer with cervical involvement preoperatively and stromal invasion on final pathology. Wilcoxon rank-sum test, Fisher exact test, Kaplan-Meier survival functions, and Cox proportional hazards models were used for analysis.ResultsNinety of 1613 patients had clinical stage II endometrial cancer; 57 underwent RH and 33 underwent SH, with no difference in adjuvant treatment or morbidity. About half of patients (51%) had pathologic stage III–IV disease. Mean follow-up was 3.3 and 3.8 years for SH and RH, respectively. Thirty-three percent of patients with RH and SH experienced a recurrence. Most recurrences were distant: 90% with SH and 79% with RH. There was no difference in RFS between groups (2-year: SH 65% vs. RH 75%; 5-year: SH 54% vs. RH 63%; P = 0.72). Controlling for stage, adjuvant treatment, and margin status, RH was not associated with RFS (HR 0.62; 95% CI 0.28–1.35). Among 44 patients with pathologic stage II disease, 7 had a recurrence (4 SH and 3 RH); 6 of 7 had distant recurrences.ConclusionsFifty-one percent of patients with clinical stage II endometrial cancer had advanced disease on final pathology, highlighting the importance of surgical staging. RH was not associated with RFS or reduced morbidity. Most recurrences were distant. Although RH could be performed to achieve negative surgical margins, SH may be sufficient for central, small tumours given the high risk of advanced disease and distant recurrence. Research efforts should further elucidate the ideal management of these patients.     

Analysis of risk factors for recurrence and effective adjuvant therapy in patients with endometrial cancer

Objective: The aim of this study was to explore risk factors for recurrence and effective adjuvant therapy in endometrial cancer.

Methods:

Methods: Between 1985 and 1999, 170 patients with uterine endometrial cancer received initial therapy at the National Defense Medical College Hospital. We retrospectively analyzed risk factors including; histopathological features, operative procedures, adjuvant therapies and surgical staging.

Results:

Results: Although the prognosis in stage I and II patients was fairly good, recurrences were observed in patients with stage Ib or worse. Vagina walls were the frequent site of recurrence. About a half of relapses which occurred within seven months after surgery were observed during adjuvant chemotherapy. Multivariate analysis revealed that myometrial invasion ( P = 0.0231) was the only risk factor for recurrence. Although the prognosis in stage III and IV patients was generally poor, serosal invasion in stage III disease seemed to be an im-portant risk factor. With regard to adjuvant therapy in stage I–III patients who could receive optimal cytoreductive surgery; the risk of recurrence was significantly ( P = 0.0127) lower in patients receiving radiation therapy than in those receiving chemotherapy including platinum agents.

Conclusion:

Conclusion: The data suggested that in stage I–III patients with optimal cytoreductive surgery, myometrial invasion is an independent risk factor for recurrence and radiation therapy is more effective than chemotherapy as adjuvant therapy.     

Potential therapeutic role of para-aortic lymphadenectomy in node-positive endometrial cancer

OBJECTIVE: The aim of this study was to assess the potential therapeutic role of para-aortic lymphadenectomy (PAL) in high-risk patients with endometrial cancer. METHODS: We studied two groups of patients with endometrial cancer who underwent operation at Mayo Clinic (Rochester, MN) during the interval 1984 to 1993: (1) 137 patients at high risk for para-aortic lymph node involvement (myometrial invasion >50%, palpable positive pelvic nodes, or positive adnexae), excluding stage IV disease, and (2) 51 patients with positive nodes (pelvic or para-aortic), excluding stage IV disease. By our definition, PAL required removal of five or more para-aortic nodes. RESULTS: In both groups, no significant difference existed between patients who had PAL (PAL+) and those who did not (PAL-) in regard to clinical or pathologic variables, percentage irradiated, or surgical or radiation complications. Among the 137 high-risk patients, the 5-year progression-free survival was 62% and the 5-year overall survival was 71% for the PAL- group compared with 77 and 85%, respectively, for the PAL+ group (P = 0.12 and 0.06, respectively). For the 51 patients with positive nodes, the 5-year progression-free survival and 5-year overall survival for the PAL- group were 36 and 42% compared with 76 and 77% for the PAL+ group (P = 0.02 and 0.05, respectively). Lymph node recurrences were detected in 37% of the PAL- patients but in none of the PAL+ patients (P = 0.01). Multivariate analysis suggested that submission to PAL was a cogent predictor of progression-free survival (odds ratio = 0.25; P = 0.01) and overall survival (odds ratio = 0.23; P = 0.006). CONCLUSIONS: These results suggest a potential therapeutic role for formal PAL in endometrial cancer.     

Reliability of sentinel node assay in vulvar cancer: the first Croatian validation trial

Objectives

To evaluate patterns of recurrence in 1988 FIGO stage IC endometrioid endometrial adenocarcinoma.

Methods

A prospectively maintained endometrial cancer database was utilized to identify all patients with stage IC endometrioid endometrial adenocarcinoma treated between 2/93 and 6/09. Patterns of recurrence and risk factors were analyzed.

Results

One hundred thirty-four patients with stage IC endometrial cancer were identified. Median age was 66 years (range, 31-91 years). All patients were initially treated surgically, and 79% underwent comprehensive surgical staging with lymphadenectomy. Median number of lymph nodes removed was 18 (range, 1-45). Fifty-one patients (38%) had FIGO grade 1 tumors, 55 (41%) had grade 2 tumors, and 28 (21%) had grade 3 tumors. The majority of patients (91%) received adjuvant radiation therapy. With a median follow-up of 36 months (range, 0.6-141.4 months), 10 patients recurred. Of these, 2 (20%) were grade 1, 2 (20%) were grade 2, and 6 (60%) were grade 3. Nine (90%) of these recurrences had a distant component and 7 (70%) were fatal. Overall, the 3 year cumulative incidence failure rate for grade 1/2 tumors was 5.4%; for grade 3 tumors it was 28.9% (P < 0.001). Age, BMI, and lymphovascular invasion were not associated with an increased risk of recurrence.

Conclusions

Patients with stage IC, grade 3 endometrial cancer had a significantly increased risk of recurrence (28.9%). All of these recurrences had a distant component and the majority were fatal. Further investigation into the addition of adjuvant systemic therapy in these high-risk patients is warranted.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.     

Analysis of vaginal recurrences in stage I endometrial adenocarcinoma

OBJECTIVE: To determine the risk of vaginal recurrence in Stage 1 endometrial cancer and treatment morbidity associated with different therapeutic approaches MATERIAL AND METHODS: Between 1995 and 2005, 341 patients with clinical Stage I endometrial cancer were treated at Istanbul Medical Faculty. One hundred and forty-four women were included in this study as the follow-ups and records were complete. The patients with no myometrial invasion received no further therapy following hysterectomy. When there was superficial myometrial invasion postoperative vaginal vault radiation was used, and if deep myometrial invasion was present, external pelvic radiation was given. RESULTS: Overall 5-year survival rate for all patients with Stage I disease was 80%. Nine patients (6.25%) developed recurrent disease, three of whom had vaginal recurrences. All three vaginal recurrences were small and diagnosed at routine follow-up exam within 51 months of primary therapy. CONCLUSION: This selective treatment protocol for patients with Stage I endometrial cancer avoided radiation entirely in 38% of the patients while achieving a very low rate of vaginal recurrence and good overall survival.     

Does oncologic specialization influence outcomes following surgery in early stage adenocarcinoma of the endometrium?

OBJECTIVE: To evaluate treatment outcomes in women with early-stage endometrial cancer (FIGO IA, IB, IC, or IIA) surgically managed by a general gynecologist (GYN) or a gynecologic oncologist (GYO). METHODS AND RESULTS: 349 women treated from 1990-2003 were studied. Median follow-up was 3.7 years. Ninety-five were classified as high-intermediate risk (HIR: stages IB grade III, IC grade II or III, any stage IIA). 110 women received adjuvant radiotherapy. The GYO group had more unfavorable tumor characteristics based on stage and grade (P<0.0001), shorter follow-up (median 3.1 vs. 5.1 years, P=0.0002), and an absolute 12% less likelihood of receiving adjuvant radiotherapy (P=0.04). Local and distant failures were not significantly different. Overall survival favored GYN patients (P=0.02) with no difference in disease-specific survival (P=0.38). Multivariate analysis for disease-free survival revealed HIR disease (P=0.04) and GYO treatment (P=0.049) to be significant, with a trend for age相似文献   

Interstitial Brachytherapy for Vaginal Recurrences of Endometrial Carcinoma

OBJECTIVE: The aim of this study was to evaluate the efficacy of interstitial brachytherapy in the management of vaginal recurrences of endometrial carcinoma. METHODS: Thirty patients received interstitial irradiation, with or without external beam radiotherapy. They were followed for a minimum of 5 years or until death. RESULTS: The median age was 66 years at initial diagnosis of endometrial cancer. FIGO stages included Stage I (n = 18), Stage II (n = 7), and Stage III (n = 5). All patients were treated originally by total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without lymphadenectomy, and 13 (43%) also received postoperative adjuvant whole pelvis radiotherapy as part of their primary treatment. Vaginal recurrences were diagnosed at a mean interval of 29 months after hysterectomy (range, 3-119 months). No patient had clinical evidence of pelvic sidewall extension or of distant metastatic disease. All patients were treated with interstitial brachytherapy; each implant delivered a mean maximal tumor dose of 25.5 Gy. Eighteen patients (60%) also received external beam radiotherapy (mean dose, 48 Gy) as part of their treatment for vaginal recurrence. Twenty-eight patients (93%) experienced a complete clinical response. Ten patients relapsed in the vagina (n = 5) or at distant sites (n = 5). Eleven patients are dead of disease. From the time of vaginal recurrence, the median overall survival was 60 months and the cause of death adjusted 5-year survival rate was 65%. Major morbidity included radiation proctitis (n = 2), fistula (n = 2), and radiation stricture (n = 1). CONCLUSION: Interstitial irradiation resulted in favorable local control as well as a 5-year survival rate and morbidity comparable to that reported previously for conventional brachytherapy.     

Conservative management of stage I endometrial carcinoma after surgical staging.

OBJECTIVE: The aim of this study was to determine the outcomes of Stage I endometrial carcinoma patients who are managed without adjuvant radiation after comprehensive surgical staging. METHODS: A computerized hospital database identified women diagnosed with adenocarcinoma of the endometrium from 1993 to 1998. A chart review identified 864 women as having primary surgery for adenocarcinoma of the endometrium. A total of 670 of 864 patients (78%) underwent comprehensive surgical staging with total hysterectomy, bilateral salpingo-oophorectomy, pelvic/para-aortic lymphadenectomy, and peritoneal cytology. After 57 patients with high-risk histologic subtypes were excluded, 613 patients remained for analysis. RESULTS: A total of 321 of 325 Stage IB patients (99%) did not receive adjuvant radiation. Fifteen of 321 patients (5%) recurred; 9 recurred in the pelvis or vagina. All 9 local recurrences were salvaged with whole pelvic radiation (XRT) and brachytherapy (BT). Seventy-seven patients were diagnosed with Stage IC disease; 53 (69%) received no adjuvant therapy. Four patients (8%) recurred, of which 2 recurred in the vagina. Three of 4 patients (75%) were salvaged, 2 with XRT/BT and 1 with surgery and chemotherapy. For all Stage I patients, the 5-year disease-free survival was 93% and the 5-year overall survival was 98%. CONCLUSIONS: Surgically staged patients with endometrial carcinoma confined to the uterine corpus have a small risk of recurrence and the majority of these recurrences can be salvaged with radiation therapy. Conservative management of Stage I endometrial carcinoma patients is an effective treatment strategy.     

Cost-effectiveness of adjuvant radiotherapy in intermediate risk endometrial cancer

OBJECTIVES: Endometrial cancer is the most common gynecologic malignancy in the United States. Adjuvant radiotherapy in patients with intermediate risk disease (stage IB, IC, and occult stage II) is controversial. Despite no proven survival advantage, a significant number of women undergo this treatment annually. The purpose of this study was to compare the estimated health and economic outcomes for adjuvant whole pelvic radiotherapy to no treatment with salvage therapy for recurrence. METHODS: A decision analytic model was created to estimate the costs of adjuvant pelvic radiotherapy versus no adjuvant radiotherapy in patients with intermediate risk endometrial cancer. Data used was gathered from published literature and institutional data on costs. The model incorporates complications, recurrence rates, treatment of recurrence, and survival in each group. RESULTS: In the base case analysis, adjuvant pelvic radiation reduced the recurrence rate by 50%. Cost-effectiveness as measured by cost per recurrence prevented was highly sensitive to the probability of recurrence and the efficacy of adjuvant therapy. In our model the mean costs of Strategy 1 with observation and treatment reserved until the time of recurrence would be $5016. In contrast the mean cost of Strategy 2 which incorporated adjuvant radiotherapy would be $21,159. Cost per recurrence prevented based on the incremental cost-effectiveness is thus $225,215. In the highest risk subgroup, using the upper limit of the 90% confidence limit of efficacy seen in GOG Protocol 99, cost/recurrence prevented was approximately $50,000. Results did not differ when using parameters solely from GOG 99 or PORTEC. CONCLUSIONS: Although adjuvant pelvic radiation does not appear to improve survival for intermediate risk endometrial cancer patients, it does prevent recurrences, at a net positive cost compared to no therapy. Data are not currently available to incorporate quality of life information into cost-effectiveness analyses. Obtaining such data would allow cost/quality-adjusted life year gained to be estimated. This information is necessary to determine if the extra costs of adjuvant radiotherapy in patients with intermediate risk endometrial cancer are acceptable by current health care policy standards.     

Outcome and Management of Pathological Stage I Endometrial Carcinoma Patients with Involvement of the Lower Uterine Segment

OBJECTIVE: The objective was to evaluate the clinicopathologic characteristics and outcome of pathologic stage I endometrial carcinoma patients with lower uterine segment (LUS) involvement. METHODS: We retrospectively reviewed the characteristics and outcomes of pathologic stage I endometrial carcinoma patients treated with primary surgery at our institution between 1988 and 1998. The significance of LUS involvement was examined with univariate and multivariate analyses. Median patient follow-up was 37.3 months. RESULTS: Of the 98 cases reviewed, 41 (42%) had LUS involvement. No differences were seen in the clinicopathologic features, extent of surgical staging, or adjuvant therapies between patients with and without LUS involvement. Univariate analysis revealed that grade, lymphovascular invasion (LVI), myometrial invasion (MI), and histology were correlated with recurrence. While the 5-year actuarial disease-free survival was worse in women with LUS involvement (80.3 vs 94.0%) compared to those without, this difference did not reach statistical significance (P = 0.14). Moreover, after controlling for pathologic features in a multivariate model, LUS involvement was not correlated with patient outcome (P = 0.98; hazard rate 0.97; 95% confidence interval 0.24, 4.0). LUS was also not correlated with pelvic recurrence. Of 25 low-risk patients (superficial MI and grade 1-2 disease) with LUS involvement, none recurred in the pelvis following surgery alone. In contrast, pelvic recurrence was common (5/12 or 41.6%) in high-risk patients (deep MI and/or grade 3 tumors) following surgery alone regardless of LUS involvement. CONCLUSION: LUS involvement is common in pathologic stage I endometrial carcinoma but is not correlated with a worse outcome. Moreover, in the absence of adverse pathologic features, LUS involvement is not associated with an increased risk of pelvic recurrence and should not be used as an indication for adjuvant radiation therapy.     

Adjuvant radiation therapy is not necessary in the management of endometrial carcinoma stage I, low-risk cases

In an attempt to create uniform nationwide guidelines for the management of all stages of endometrial carcinoma, and to limit the use of adjuvant radiation therapy in stage I disease to high-risk patients only, a protocol was developed by the Danish Endometrial Cancer group (DEMCA). From September 1986 through August 1988, 1214 women in Denmark with newly diagnosed carcinoma of the endometrium have been treated according to this protocol. This figure represents all endometrial carcinomas diagnosed in Denmark during this 2-year period. The primary treatment was total abdominal hysterectomy and bilateral salpingo-oophorectomy and no preoperative radiation therapy was delivered. In 1039 cases no macroscopic residual tumor and/or microscopic tumor tissue in the resection margins was found following surgery. Based on surgery and histopathology, these patients were classified as: P-stage I low-risk (grade 1 & 2 and 50% myometrial invasion), P-stage I high-risk (grade 1 & 2 and> 50% myometrial invasion, and grade 3), P-stage II and P-stage III (Group 1). Distribution was as follows: P-I low-risk 641 patients, P-I high-risk 235, P-II 105 and P-III (Group 1) 58 patients. No postoperative radiation therapy was given to P-I low-risk cases. P-I high-risk, P-II, and P-III (Group 1) cases received external radiation therapy. Recurrence rate at 68–92 months follow-up was 45/641 (7%) in P-I low-risk, 36/235 (15%) in P-I high-risk, 30/105 (29%) in P-II, and 27/58 (47%) in P-III (Group 1) cases. Fifteen of 17 vaginal recurrences in P-I low-risk cases were salvaged (mean observation time 61 months).     

Conservative treatment may be beneficial for young women with atypical endometrial hyperplasia or endometrial adenocarcinoma

OBJECTIVE: To evaluate whether an alternative treatment to radical hysterectomy exists for young women with endometrial adenocarcinoma. DESIGN: A review of the literature (70 articles) plus personal results. SETTING: University hospital. PATIENT(S): Women with atypical endometrial hyperplasia or adenocarcinoma. MAIN OUTCOME MEASURE(S): The recurrence rate and the pregnancy rate after conservative therapy. CONCLUSION(S): Conservative treatment of well-differentiated stage I endometrial adenocarcinoma can be considered in young patients, with close surveillance to diagnose any possible recurrence.