Survival of women with surgical stage II endometrial cancer.

OBJECTIVE: The aim of this study was to report survival and determine prognostic factors and results of therapy in women with surgical stage II endometrial cancer. METHODS: Forty-eight consecutive women with surgical stage II endometrial cancer treated at the University of Vermont between March 1984 and March 1998 were reviewed. Patients' characteristics, surgical procedure, postoperative treatment and its complications, and tumor recurrence and its treatment were recorded. In addition, a formal review of their pathological material for confirmation of the diagnosis was performed. RESULTS: The median duration of follow-up was 6.2 years. Three patients (6.3%) had tumor recurrence and two (4.2%) died of their disease. The estimated 5-year overall survival and disease-free survivals were 92.1% (SE = 5.5%, 95% confidence interval: 81.3, 100%) and 89.9% (SE = 5.8%, 95% confidence interval: 78.5%, 100%), respectively. None of the patients treated by total abdominal hysterectomy followed by both whole pelvic and vaginal cuff radiation therapy (the main line of treatment for patients in whom cervical involvement was diagnosed following hysterectomy, n = 20) or by radical hysterectomy (the main line of treatment for patients in whom cervical involvement was known before hysterectomy, n = 11) had tumor recurrence. Three of 17 (17.6%) patients treated with total abdominal hysterectomy followed by either whole pelvic (n = 13) or vaginal cuff (n = 4) radiation therapy had tumor recurrence. The difference between those two groups was statistically significant (0/31 versus 3/17, P = 0.02). There was no difference in survival among women with stage IIA and IIB or women who underwent radical abdominal hysterectomy and those who underwent total abdominal hysterectomy with postoperative pelvic and vaginal cuff radiation. Morbidity secondary to therapy was mild. Age, depth of myometrial invasion, tumor histology, and grade were not significantly related to recurrence. CONCLUSIONS: Survival of women with surgical stage II endometrial cancer is excellent especially among those treated with total abdominal hysterectomy followed by both pelvic and vaginal cuff radiotherapy or by radical abdominal hysterectomy.     

Surgical treatment of unexpected invasive cervical cancer found at total hysterectomy.

OBJECTIVE: To determine the proper management of patients found to have invasive cancer of the cervix on pathologic examination of a uterus removed for benign indications. METHODS: We report 18 patients undergoing hysterectomy who were found to have cervical cancer with invasion deeper than 3 mm and/or lymph-vascular space involvement. None had gross residual tumor following simple hysterectomy. All patients underwent a second operation. Seventeen women underwent a radical parametrectomy, upper vaginectomy, and pelvic lymphadenectomy; one had pelvic and periaortic lymphadenectomy alone because of bilateral grossly positive obturator nodes. RESULTS: Median follow-up was 72 months. One of the 15 women without residual disease or nodal involvement at second operation had pelvic recurrence 66 months after therapy. Three patients with disease identified at radical surgery underwent tailored postoperative pelvic radiation, and two of these had pelvic recurrence. The overall actuarial 5-year survival for the 18 patients was 89%. Operative morbidity was comparable to that of patients undergoing primary radical hysterectomy. CONCLUSION: This study confirms that patients with unexpected invasive cervical cancer found at total hysterectomy can undergo radical re-operation with low morbidity and excellent cure rates.     

Analysis of treatment outcome in patients with endometrial cancer limited to the uterus

OBJECTIVES: The aim of study was to analyse results of treatment patients with uterine-confined endometrial cancer which underwent surgery and postoperative radiotherapy in Center of Oncology in Kraków between 1985 and 1997. MATERIAL AND METHODS: The research included a group of 650 women. All patients undergo total abdominal hysterectomy with bilateral salpingo-oophorectomy and postoperative radiotherapy. 155 patients with intermediate-risk of recurrence (IA-G3, IB-G1, G2) received postoperative whole pelvic irradiation only. In the group of 495 patients with high-risk of recurrence (IB-G3, IC, II) 210 patients received brachytherapy vaginal cuff only and 285 patients whole pelvic and vaginal cuff irradiation. RESULTS: In the group of patients with intermediate-risk of recurrence five NED survival was 93.5%. In the group of patients with high-risk of recurrence five NED survival was statistically lower in patients treated with brachytherapy vaginal cuff only (83.2% vs. 71.9%). CONCLUSION: In uterine-confined endometrial cancer patients, with intermediate-risk of recurrence treated with surgery and postoperative whole pelvis irradiation, 5-year NED survival is above of 90%. In the group of patients with high-risk of recurrence the adjuvant treatment of choice is whole pelvic and vaginal cuff irradiation.     

Improved survival in surgical stage I patients with uterine papillary serous carcinoma (UPSC) treated with adjuvant platinum-based chemotherapy

OBJECTIVE: Uterine papillary serous carcinoma (UPSC) is an aggressive form of endometrial cancer characterized by a high recurrence rate and a poor prognosis. Prior studies evaluating treatment of UPSC have been limited by small numbers of patients and inclusion of partially staged patients. The purpose of this study was to evaluate the efficacy of adjuvant platinum-based chemotherapy and vaginal cuff radiation in a large cohort of surgical stage I UPSC patients. METHODS: We retrospectively reviewed 74 stage I patients with UPSC who underwent complete surgical staging at our institution between 1987 and 2004. RESULTS: Stage IA patients were divided into two groups: patients with no cancer in the hysterectomy specimen (defined as no residual uterine disease) and patients with cancer in the hysterectomy specimen (defined as residual uterine disease). Stage IA patients with no residual uterine disease had no recurrences, regardless of adjuvant therapy (n = 12). Stage IA patients with residual uterine disease who were treated with platinum-based chemotherapy had no recurrences (n = 7). However, 6 of 14 (43%) stage IA patients with residual uterine disease who did not receive chemotherapy recurred. The 15 patients with stage IB UPSC who received platinum-based chemotherapy had no recurrences but 10 of the 13 (77%) stage IB patients who did not receive chemotherapy recurred. One of the 7 patients with stage IC UPSC who received platinum-based chemotherapy recurred and 4 of the 5 (80%) stage IC patients who did not receive chemotherapy recurred. Overall platinum-based chemotherapy was associated with improved disease-free survival (P < 0.01) and improved overall survival (P < 0.05) in patients with stage I UPSC. None of the 43 patients who received radiation to the vaginal cuff recurred locally, but 6 of the 31 (19%) patients who were not treated with vaginal radiation recurred at the cuff. CONCLUSIONS: Platinum-based chemotherapy improves the disease-free and overall survival of patients with stage I UPSC and vaginal cuff radiation provides local control. Stage IA UPSC patients with no residual uterine disease can be observed but concomitant platinum-based chemotherapy and vaginal cuff radiation (referred to as chemoradiation) should be offered to all other stage I UPSC patients.     

Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: a Gynecologic Oncology Group study

Between June 20, 1977 and February 5, 1983, the Gynecologic Oncology Group entered 1180 women with clinical stage I or II (occult) endometrial carcinoma into a surgical-pathological staging study. Eight hundred ninety-five patients with endometrioid or adenosquamous carcinoma were evaluable for this study which relates surgical-pathological parameters and postoperative treatment to recurrence-free interval and recurrence site. Proportional hazards modeling of time to recurrence was performed. For patients without metastasis determined by surgical-pathological staging the greatest determinant of recurrence was grade 3 histology adenocarcinoma grade 3, relative risk (RR) = 15; adenosquamous carcinoma grade 3, RR = 8.1; all adenocanthomas, RR = 1.0). Of 48 patients with histologically documented aortic node metastases, 47 had one or more of the following features: (1) grossly positive pelvic nodes, (2) grossly positive adnexal metastasis, or (3) outer one-third myometrial invasion. Pelvic radiation was administered to 48.0% and vaginal brachytherapy alone to 10.2% of patients postoperatively; 41.8% received no adjuvant radiation therapy. None of three recurrences in the vaginal implant group were vaginal or pelvic; 7.4% (7 of 95) of recurrences in the pelvic radiation therapy (RT) group were vaginal and 16.8% were pelvic; 18.2% (8 of 44) of recurrences in the no adjuvant radiation group were vaginal and 31.8% pelvic. Because of the high degree of selection bias no valid comparisons can be made of recurrence-free interval in these groups. The 5-year recurrence-free interval for patients with negative surgical-pathological risk factors (other than grade and myoinvasion) was 92.7%; involvement of the isthmus/cervix 69.8%; positive pelvic cytology 56.0%; vascular space invasion 55.0%; pelvic node or adnexal metastases 57.8%; and aortic node metastases or gross laparotomy findings 41.2%. It is not clear that cervix invasion per se diminishes survival, because it is more often associated with poor tumor differentiation (34.7% versus 24.0%, grade 3) and deep myoinvasion (47.0 vs 18.6%) than cases without cervix invasion. The relapse rate among cervix-positive and -negative cases with grade 3 lesions and deep myoinvasion is not dramatically different (48.8% vs 39.8%). The proportion of failures which were vaginal/pelvic (34.6% for the surgery only group compared to 12.5% of the RT group) appears to favor the use of adjuvant radiation for patients with more than one-third myoinvasion and grade 2 or 3 tumor. There were 97 patients in the study group with malignant cytology of which 29.1% had regional/distant failure, which compares to 10.5% of the cytology-negative patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

FIGO stage IIIC endometrial carcinoma with metastases confined to pelvic lymph nodes: analysis of treatment outcomes, prognostic variables, and failure patterns following adjuvant radiation therapy.

OBJECTIVES: This study was undertaken to evaluate the prognostic significance of isolated positive pelvic lymph nodes on survival and to analyze other prognostic variables, overall survival, and failure patterns in surgically staged endometrial carcinoma patients with positive pelvic lymph nodes and negative para-aortic lymph nodes following radiation therapy (RT). METHODS: Between January 1, 1987, and December 31, 1997, 782 women underwent primary treatment for uterine cancer at Indiana University Medical Center. Through a review of the medical records, we identified 58 patients with pathologic stage IIIA, 27 patients with pathologic stage IIIB, and 77 patients with pathologic stage IIIC endometrial carcinoma. Patients with pathologically positive or unsampled para-aortic lymph nodes and patients who received preoperative radiation therapy were excluded, leaving a study group of 17 patients with nodal metastases confined to pelvic lymph nodes. Thirteen patients received adjuvant pelvic RT using AP-PA or four-field technique. A median dose of 5040 cGy was delivered. Four patients received whole abdominal irradiation (WAI) delivering a median dose of 3000 cGy. Two patients received vaginal cuff boosts of 1000 and 3560 cGy to 0.5 cm from the vaginal surface mucosa via Cs-137 brachytherapy. Two patients also received adjuvant chemotherapy (cis-platinum and doxorubicin) and/or hormonal therapy (megestrol acetate). Disease-free and overall survivals were estimated using the Kaplan-Meier method of statistical analysis and prognostic variables were analyzed using the log-rank test. RESULTS: With a median follow-up of 51 months the actuarial 5-year disease-free survival was 81% and the actuarial 2-year and 5-year overall survival rates were 81 and 72%, respectively. Univariate analysis revealed that positive peritoneal cytology in conjunction with positive pelvic lymph nodes imparts a greater risk of recurrence and decreased overall survival. There were no pelvic and/or upper abdominal failures, but there were recurrences in the para-aortic lymph nodes (two patients) and distantly (two patients). CONCLUSION: Surgery followed by postoperative pelvic RT is a viable treatment option for pathologically staged stage IIIC endometrial carcinoma with disease confined to the pelvic lymph nodes. Failures in the para-aortic region suggest a possible role for extended-field RT. Patients with positive peritoneal cytology in conjunction with nodal metastasis fared poorly with pelvic RT. Studies evaluating the efficacy of WAI are ongoing. Finally, substages within FIGO stage IIIC are recommended in an effort to better understand and define treatment strategies which might be appropriate for these patients.     

Postoperative pelvic radiotherapy for cervical cancer patients with positive parametrial invasion

OBJECTIVE: To evaluate patterns of failure in cervical cancer patients with histopathologic parametrial invasion treated with postoperative pelvic radiation therapy. METHODS: Records of 117 stages IB-IIB cervical cancer patients with parametrial invasion treated with postoperative radiation therapy from 1985 to 2002 were retrospectively reviewed. Patients were divided into two groups based on status of pelvic lymph nodes. Patterns of recurrence and prognosis by status of pelvic lymph nodes were statistically analyzed. RESULTS: Status of pelvic lymph nodes had significant impact on both recurrence and survival. Extrapelvic recurrence was observed in 23 of 66 node-positive patients compared with 6 of 51 node-negative patients (P = 0.005). Of 66 patients with a positive pelvic lymph node, 18 developed visceral metastases, whereas only three visceral metastases were noted in the 51 node-negative patients (P = 0.003). Five-year overall survival in node-positive and -negative patients was 52% and 89%, respectively (P = 0.0005). Corresponding rates for recurrence-free survival were 44% and 83%, respectively (P = 0.0002). The correlation between nodal metastasis and prognosis was enhanced when node-positive patients were stratified into two groups based on number of positive nodes (n = 1 and n > or = 2). Five-year recurrence-free survival rates for patients with negative, one positive, and two or more positive nodes were 83%, 61%, and 31%, respectively (P = 0.0001). CONCLUSIONS: Extrapelvic recurrence was uncommon in node-negative patients with parametrial invasion. These findings do not support use of systemic therapy for cervical cancer patients with parametrial invasion if pelvic lymph node metastasis is negative.     

Prognostic factors in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy

OBJECTIVE: The purpose of the present study was to identify prognostic factors and recurrent patterns in pathologic parametrium-positive patients with stage IB-IIB cervical cancers treated by radical surgery and adjuvant therapy. METHODS: The patient population consisted of 84 individuals presenting with stage IB-IIB cervical cancers and histologically proven parametrial invasion. All these patients were treated postoperatively with adjuvant external whole pelvic irradiation, combination chemotherapy, or chemoradiotherapy. RESULTS: The 5-year disease-free survival rate was found to be 67.2% and 5-year overall survival rate, 75.4%. Multivariate analysis revealed that vaginal invasion (p=0.0008), lymph node metastasis (p=0.002), and non-squamous histology (p=0.010) were independent indicators of the disease-free survival rates and that the vaginal invasion (p=0.009) and lymph node metastasis (p=0.011) were independent prognostic factors for the overall survival rates. The 5-year overall survival rate was approximately 90% for patients without these risk factors. Disease recurrence was observed in 26 patients (31.0%) with a median time of 16.5 months (range, 5-59 months) from the surgery. Hematogenous recurrences, including those in the lung, liver, and bone, were significantly higher in patients with non-squamous cell carcinomas (p=0.008). Distant lymph node recurrences were significantly higher in patients with positive pelvic lymph node and vaginal invasion (p=0.004 and p=0.023, respectively). Pelvic recurrences were significantly higher in patients with vaginal invasion (p=0.026). CONCLUSIONS: Vaginal invasion and lymph node metastasis are independent indicators for disease-free and overall survival rates in pathologic parametrium-positive patients with stage IB-IIB cervical cancer treated by radical surgery and adjuvant therapy. The survival rate is excellent in the patients without these risk factors. Hematogenous recurrence may be evident in patients with non-squamous cell carcinomas.     

Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients

OBJECTIVE: The aim of this study was to analyze FIGO Stage IIIc endometrial cancer (EC) patients to better define clinicopathologic associations, patterns of failure, and survival. METHODS: Charts were abstracted from EC patients with lymph node metastasis from 1989 to 1998. Data on clinicopathologic variables, adjuvant treatment, site of first recurrence, and survival were collected. Associations between variables were tested by chi(2) and Wilcoxon rank sums. Survival analyses were performed by the Kaplan-Meier method, and multiple regression analysis was done by the Cox proportional hazards model. RESULTS: From 607 EC patients evaluated, 47 (8%) were identified with FIGO Stage IIIc disease. All 47 underwent hysterectomy and pelvic lymph node (PLN) sampling, and 42/47 had para-aortic lymph node (PALN) sampling. Stage IIIc disease was defined by positive PLN alone in 38%, positive PLN and PALN in 41%, and positive PALN alone in 17%. Twelve of 47 also had positive peritoneal cytology and/or adnexal metastases. Grade III tumors were present in 56% and >50% myometrial invasion in 61%. No association between depth of invasion (DOI) and grade was seen, however. Nearly 1/3 of cases had papillary serous or clear cell histology. Postoperative adjuvant treatment included whole abdominal radiation (36%), pelvic radiation with (19%) and without (17%) extended field, chemotherapy (17%), and oral progestins (11%). The 3-year and 5-year survival estimates for all patients were 77 and 65%, respectively. At a median follow-up of 37 months, 5 patients are alive with disease, and 10 are dead of disease. A distant site of first recurrence was most common (21%), followed by pelvic failure (9%). Only 1 patient has had an abdominal recurrence. Univariate predictors of survival included age, DOI, and extranodal disease, but not grade, histology, or PALN involvement. For the 12 patients with nodal disease and positive cytology and/or adnexa, 3-year survival was 39% versus 93% for those patients without evidence of extranodal disease. In a multivariate analysis only DOI was an independent predictor of survival (P = 0.03). CONCLUSIONS: Once lymph node involvement occurs, the importance of additional extranodal disease increases. Consideration of substaging Stage IIIc patients based on positive adnexa or cytology is supported by the data. The extent which adjuvant treatments contributed to the 77% 3-year survival remains to be defined. The patterns of failure suggest a possible role for combined modalities in future treatments.     

Outcomes after definitive re-irradiation with 3D brachytherapy with or without external beam radiation therapy for vaginal recurrence of endometrial cancer

BackgroundLimited outcome data exists on salvage re-irradiation for vaginal relapse of previously-irradiated endometrial cancer. We report our 10-year experience with management of vaginal recurrence using definitive intent re-irradiation brachytherapy with or without EBRT.MethodsA retrospective review was performed on 22 patients treated with definitive-intent re-irradiation brachytherapy ± EBRT for vaginal recurrence of endometrial cancer. The cumulative rectosigmoid and bladder D2cc (EQD2) were limited to <75 Gy and <90 Gy, respectively. Kaplan-Meier and Cox proportional hazards modeling were used to estimate survival. Severe (grade 3 or higher) radiation-related toxicities, defined according to CTCAE v4, were recorded.ResultsPrior radiation therapy consisted of vaginal brachytherapy (54.5%), pelvic EBRT (22.7%), or combination pelvic EBRT and brachytherapy (22.7%). Median re-irradiation interval was 26.6 months. Salvage re-irradiation consisted of EBRT with brachytherapy in 50.0% and brachytherapy alone in 50.0%. Median HR-CTV D90 (EQD2) was 64.5 Gy (IQR: 49.6–75.8). Median cumulative D2cc for bladder, rectum, and sigmoid were 72.1 Gy (range: 30.3–81.8), 70.6 Gy (range: 32.0–80.5), and 52.7 Gy (range: 29.6–75.3), respectively. At a median follow-up of 27.6 months, 3-year local control, regional control, disease-free survival, and overall survival rates were 65.8%, 76.6%, 40.8%, and 68.1%, respectively. There were no grade ≥ 3 acute or late rectosigmoid or bladder toxicities.ConclusionRe-irradiation with 3D conformal brachytherapy for vaginal recurrence is feasible and safe as long as cumulative dose to surrounding normal organs is limited, and offers a chance to potentially salvage 40% of patients presenting with vaginal recurrence in the setting of prior pelvic radiation.     

The role of radiation therapy in early endometrial cancer.

Few randomized studies have addressed the best choice of adjuvant radiation therapy after surgery for stage I endometrial cancer. Although whole pelvic radiation decreases the incidence of pelvic and vaginal cancer recurrence, there is no convincing evidence that it improves survival in women who have been completely staged. Several studies have indicated that women with high-risk stage I endometrial adenocarcinoma are treated adequately with extended surgical staging and vaginal cuff radiation. In the absence of randomized trials suggesting that whole pelvic radiation improves survival, it should be limited only to the highest risk stage I subgroups. Vaginal cuff brachytherapy appears to provide excellent local control of disease with minimal morbidity.     

Predicting pelvic lymph node metastasis in endometrial carcinoma

BACKGROUND: To determine the possibility of individualizing the pelvic lymph node dissection in patients with endometrial cancer, the relationship between pelvic lymph node (PLN) metastasis and various prognostic factors was retrospectively investigated. METHODS: From 1979 to 1994, 175 patients with endometrial carcinoma were treated with either total or radical hysterectomy combined with a PLN dissection as initial therapy. The prognostic factors examined included clinical stage, patient age, histological grade, the microscopic degree of myometrial invasion (DMI), cervical invasion, adnexal metastasis, and macroscopic tumor diameter (TD). RESULTS: Of the 175 patients undergoing PLN dissection, 24 (14%) had PLN metastasis. An endometrial cancer with PLN metastasis had a significantly longer diameter than those without PLN metastasis. The frequency of PLN metastasis increased along with increases in tumor diameter. A logistic regression analysis revealed DMI and TD to be independently correlated with PLN metastasis. The formula based on the coefficients of TD and DMI obtained from the analysis also showed a good correlation, which allowed us to estimate the probability of patients having PLN metastasis. CONCLUSIONS: DMI and TD could accurately estimate the status of PLN in endometrial carcinoma patients.     

Adjuvant therapy for stage I uterine sarcoma

A retrospective evaluation of adjuvant therapy in 64 patients with Stage I sarcoma was undertaken. A combination of operation and adjuvant radiation was compared with operation alone. A decreased recurrence of both pelvic and distant tumor was noted for endometrial sarcoma but not for leiomyosarcoma treated with adjuvant radiation. A Cox regression analysis showed a trend for improved survival, but the results were not statistically significant. Survival after vaginal cuff recurrence and treatment with radiation therapy (two patients) or combined radiation and chemotherapy (one patient) is reported. Seven patients received adjuvant chemotherapy with Adriamycin-based regimens. Chemotherapy alone did not statistically decrease recurrence in this small sample.     

子宫颈鳞癌Ⅰb～Ⅱa期患者预后预测系统的建立及其临床意义

目的分析子宫颈鳞癌Ⅰb~Ⅱa期患者的预后影响因素并建立预后预测系统,以探讨其在指导术后辅助治疗中的作用。方法回顾性分析接受手术治疗的306例Ⅰb~Ⅱa期宫颈鳞癌患者的临床病理资料,对影响其预后的因素进行单因素和多因素分析。结果306例患者的5年生存率为78 1%。单因素分析结果显示,与其预后有关的因素为淋巴结转移、病理分化程度、肿瘤直径、宫旁组织浸润、深肌层浸润和脉管内瘤栓(P<0 05);多因素分析结果显示,淋巴结转移、深肌层浸润、宫旁组织浸润是影响其预后的独立危险因素(P<0 05)。根据危险因素的不同建立预后预测系统,即将患者分为低危组、中危组和高危组3组,其5年生存率分别为90 3%、83 9%和43 1%。低危组(无危险因素或仅宫旁组织浸润)局部复发的发生率仅为2 2%;中危组(深肌层浸润或合并有宫旁组织浸润)局部复发的发生率为13 5%,远处转移的发生率为1 3%, 局部复发合并远处转移的发生率为0 6%;高危组(淋巴结转移或合并其他危险因素)局部复发和远处转移的发生率分别为25 9%和48 3%,局部复发合并远处转移的发生率为10 3%。结论淋巴结转移、深肌层浸润、宫旁组织浸润是影响Ⅰb~Ⅱa期宫颈鳞癌患者预后的独立因素;根据预后影响因素建立的预后预测系统有助于指导术后辅助治疗。     

Randomized study of preoperative radiation and surgery or irradiation alone in the treatment of stage IB and IIA carcinoma of the uterine cervix: final report

A prospective randomized study in selected patients with Stage IB and IIA carcinoma of the uterine cervix was carried out at Washington University between January 1966 and December 1979. Patients were randomized to be treated with irradiation alone consisting of 1000 cGy whole pelvis, additional 4000 cGy to the parametria with a step wedge midline block, and two intracavitary insertions for 7500 mgh; or irradiation and surgery, consisting of 2000 cGy whole pelvis irradiation, one intracavitary insertion for 5000-6000 mgh followed 2 to 6 weeks later by a radical hysterectomy with pelvic lymphadenectomy. A total of 40 patients with Stage IB and 16 with Stage IIA were randomized to be treated with irradiation alone. A similar group of 48 patients with Stage IB and 14 with IIA were randomized to the preoperative radiation and surgery group. The 5-year, tumor-free actuarial survival for Stage IB patients treated with radiation was 89% and with preoperative radiation and surgery 80%. In Stage IIA, the tumor-free actuarial 5-year survival was 56% for the irradiation alone group and 79% for the patients treated with preoperative radiation and radical hysterectomy. In the patients with Stage IB treated by irradiation alone only one pelvic failure combined with distant metastasis occurred, and 3 patients developed distant metastasis. In the 48 patients treated with combined therapy, there were six pelvic failures (12.5%) all combined with distant metastases and two distant metastases alone. In the 16 patients with Stage IIA treated with radiotherapy alone, there were four pelvic failures (all parametrial), three of them combined with distant metastasis. In the 14 patients treated with irradiation and surgery, two developed a pelvic recurrence, and one distant metastasis. In the preoperative radiation group, the incidence of metastatic pelvic lymph nodes was 6.3% in Stage IB and 7.1% in Stage IIA. Major complications of therapy in the patients treated with radiation alone (10%) consisted of one rectovaginal fistula, two vesicovaginal fistulas, and one rectal stricture. In the preoperative radiation group, three ureteral strictures and two severe proctitis-rectal strictures were noted (8%). The present study shows no significant difference in therapeutic results or morbidity for invasive carcinoma of the uterine cervix Stage IB or IIA treated with irradiation alone or combined with a radical hysterectomy and lymphadenectomy.     

Management of endometrial cancer with suspected cervical involvement

The 1989 International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer cells for operative assessment of the extent of uterine disease, grade, and sites of metastasis before assigning a stage to the cancer. In the current study, 70 endometrial cancer patients with suspected cervical involvement based on a positive endocervical curettage or punch biopsy were treated with initial surgery followed by tailored radiation or chemotherapy. Only 37% of the patients had operative findings consistent with the preoperative suspicion of stage II disease. Postoperative therapy was determined by the extent of cervical involvement, depth of myometrial invasion, cell type, tumor grade, and the presence and location of extra-uterine disease. Based upon these parameters, 21 patients were believed to have low risk for pelvic recurrence and received no adjuvant therapy (90% 5-year survival); 38 patients received postoperative pelvic radiation because of high-risk factors for pelvic recurrence or pelvic nodal involvement (65% 5-year survival); and 11 patients received chemotherapy and/or extended radiation because of extrapelvic disease (no 5-year survivors). The approach outlined supports initial surgery for cases of endometrial cancer with suspected cervical involvement. This approach permits accurate surgical staging under the new FIGO system, avoids radiotherapy in many patients whose disease is less extensive than suspected preoperatively, and can accomplish good local control with limited morbidity.     

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.     

External pelvic radiation therapy in stage IC endometrial carcinoma

OBJECTIVE: To evaluate outcomes of patients with stage IC endometrial carcinoma treated with external whole pelvic radiation but not vaginal brachytherapy. METHODS: Sixty-one women with stage IC endometrial carcinoma had postoperative pelvic radiation without vaginal brachytherapy. The median age was 69 years (range 44-87 years). Most subjects had histologic findings of adenocarcinoma (71%) and grade 2 or 3 disease (74%). The median pelvic irradiation dose was 48.6 Gy (range 43.2-50.4 Gy). No patients received adjuvant chemotherapy or hormonal therapy. The median follow-up time was 69.5 months (range 7-196 months). RESULTS: The 5-year actuarial disease-free and overall survivals of the entire group were 86.7% and 97.6%, respectively. No patient developed local (vaginal) recurrence. One patient had recurrent disease in the lateral pelvis. Ten patients (16.4%) had distant (extrapelvic) metastases. No serious sequelae were noted, including vaginal necrosis, small bowel obstruction, proctitis, or fistulae. CONCLUSION: Local control was excellent in stage IC endometrial carcinoma treated with adjuvant radiation therapy alone. Attention needs to be focused on efforts to control extrapelvic recurrence in patients with this disease.     

Doxorubicin as an adjuvant following surgery and radiation therapy in patients with high-risk endometrial carcinoma, stage I and occult stage II: a Gynecologic Oncology Group Study

The Gynecologic Oncology Group studied the use of adjuvant doxorubicin after surgery and radiation therapy for endometrial carcinoma in a randomized, prospective manner. The study population consisted of patients clinically stage I or II (occult) who, after surgical-pathologic evaluation, had one or more risk factors for recurrence: greater than 50% myometrial invasion, pelvic or aortic node metastasis, cervical involvement, or adnexal metastases. All patients without aortic node metastasis received 5000 rads to the whole pelvis at 160-180 rads per day. If aortic node metastasis was documented, aortic field radiation to the top of T12 was offered. The aortic target dose was 4500 rads at 150 rads per day. After completion of radiation therapy, the patients were randomized to receive doxorubicin bolus therapy (60 mg/m2 starting dose) to a maximum cumulative dose of 500 mg/m2. Between November 1977 and July 1986, 92 patients were entered into the doxorubicin (DOX) treatment arm, and 89 patients entered the no-DOX arm. There was no statistically significant difference in survival or progression-free interval of the two arms. The 5-year survival rates for patients with deep myometrial invasion, cervical involvement, and pelvic node metastases were similar (63-70%), whereas the rate for patients with aortic node metastases was 26%. There was no significant difference in the recurrence pattern between the two treatment arms. There were no cases of grade 3 or 4 cardiac toxicity. Twelve patients (6.9%) developed small bowel obstruction after radiation therapy. There were three treatment-related deaths in the DOX arm and two in the radiation therapy-only arm. We conclude that, because of protocol violations, small sample size, and the number of patients lost to follow-up, this study was unable to determine what effect use of doxorubicin as adjuvant therapy had on recurrence, progression, and survival of the endometrial cancer study population. The combination of surgical staging and postoperative radiation as used in this study appears to increase the risk of bowel complications.     

Survival after relapse in patients with endometrial cancer: results from a randomized trial

OBJECTIVE: The aim of this study was to determine the rates of local control and survival after relapse in patients with stage I endometrial cancer treated in the multicenter randomized PORTEC trial. METHODS: The PORTEC trial included 715 patients with stage 1 endometrial cancer, either grade 1 or 2 with deep (>50%) myometrial invasion or grade 2 or 3 with <50% invasion. In all cases an abdominal hysterectomy was performed, without lymphadenectomy. After surgery, patients were randomized to receive pelvic RT (46 Gy) or no further treatment. RESULTS: The analysis was done by intention-to-treat. A total of 714 patients were evaluated. At a median follow-up of 73 months, 8-year actuarial locoregional recurrence rates were 4% in the RT group and 15% in the control group (P < 0.0001). The 8-year actuarial overall survival rates were 71 (RT group) and 77% (control group, P = 0.18). Eight-year rates of distant metastases were 10 and 6% (P = 0.20). The majority of the locoregional relapses were located in the vagina, mainly in the vaginal vault. Of the 39 patients with isolated vaginal relapse, 35 (87%) were treated with curative intent, usually with external RT and brachytherapy, and surgery in some. A complete remission (CR) was obtained in 31 of the 35 patients (89%), and 24 patients (77%) were still in CR after further follow-up. Five patients subsequently developed distant metastases, and 2 had a second vaginal recurrence. The 3-year survival after first relapse was 51% for patients in the control group and 19% in the RT group (P = 0.004). The 3-year survival after vaginal relapse was 73%, in contrast to 8 and 14% after pelvic and distant relapse (P < 0.001). At 5 years, the survival after vaginal relapse was 65% in the control group compared to 43% in the RT group. CONCLUSION: Survival after relapse was significantly better in the patient group without previous RT. Treatment for vaginal relapse was effective, with 89% CR and 65% 5-year survival in the control group, while there was no difference in survival between patients with pelvic relapse and those with distant metastases. As pelvic RT was shown to improve locoregional control significantly, but without a survival benefit, its use should be limited to those patients at sufficiently high risk (15% or over) for recurrence in order to maximize local control and relapse-free survival.