Endometrial carcinoma

Opinion statement Endometrial cancer is a common tumor of the female genital tract. The majority of women diagnosed with endometrial cancer present with early-stage disease. Although the optimal treatment for these patients requires hysterectomy, the use of lymphadenectomy is controversial. Growing scientific data support the use of lymphadenectomy in all patients diagnosed with endometrial cancer. When performed by an experienced surgeon, pelvic and para-aortic lymphadenectomy is a safe and potentially therapeutic procedure that provides prognostic information to the patient and physician. This information allows appropriate, cost-effective treatment strategies to be created for all women with endometrial cancer.     

Outcome of high-risk stage IC, grade 3, compared with stage I endometrial carcinoma patients: the Postoperative Radiation Therapy in Endometrial Carcinoma Trial.

PURPOSE: Stage IC, grade 3 endometrial cancer is regarded as a high-risk category. Stage IC, grade 3 patients were not eligible for the randomized Postoperative Radiation Therapy in Endometrial Carcinoma (PORTEC) trial, but were registered and received postoperative radiotherapy. PATIENTS AND METHODS: The PORTEC trial included 715 patients with stage IC, grade 1 or 2, and stage IB, grade 2 or 3 endometrial cancer. Patients were randomly assigned after surgery to receive pelvic radiotherapy (RT) or no further treatment. A total of 104 patients with stage IC, grade 3 endometrial cancer were registered, of whom 99 could be evaluated. Patterns of relapse and survival were compared with PORTEC patients receiving RT. Median follow-up was 83 months. RESULTS: The actuarial 5-year rates of locoregional relapse were 1% to 3% for PORTEC patients who received RT, compared with 14% for stage IC, grade 3 patients. Five-year distant metastases rates were 3% to 8% for grade 1 and 2 tumors; 20% for stage IB, grade 3 tumors; and 31% for stage IC, grade 3 tumors. Overall survival rates were 83% to 85% for grades 1 and 2; 74% for stage IB, grade 3; and 58% for stage IC, grade 3 patients (P <.001). In multivariate analysis grade 3 was the most important adverse prognostic factor for relapse and death as a result of endometrial cancer (hazard ratios, 5.4 and 5.5; P <.0001). CONCLUSION: Patients with stage IC, grade 3 endometrial carcinoma are at high risk of early distant spread and endometrial carcinoma-related death. Novel strategies for adjuvant therapy should be explored to improve survival for this patient group.     

Aggressive stage I grade 1 endometrial carcinoma.

BACKGROUND. Patients with Stage I Grade 1 endometrial carcinoma have an excellent prognosis and a 10-year survival rate of more than 90%. In every clinical series, however, a few patients in this group have recurrence and die of their disease. METHODS. The authors reviewed 80 patients with Stage I Grade 1 endometrial carcinoma treated at their institution from 1955-1980. Eight patients died of recurrent disease within 4 years of diagnosis. The authors studied multiple clinical and histopathologic features, estrogen receptor (ER) and progesterone receptor (PR) status, DNA flow cytometric characteristics, and the expression of c-myb, H-ras, and neu oncogenes. Results were compared with those for a control group of 11 patients who survived more than 10 years free of disease. RESULTS. The authors identified the following four statistically significant adverse prognostic factors: myometrial invasion, vascular invasion, 8 or more mitoses per 10 high-power fields, and an absence of PR. Residual tumor, aneuploidy, and high proliferative activity were associated with a more aggressive behavior, although the relationship did not reach statistical significance. CONCLUSIONS. All patients who died of disease within 4 years had tumors with two or more of the significant adverse prognostic factors.     

The management of clinical stage I endometrial carcinoma

A retrospective analyses of 307 cases with clinical Stage I endometrial carcinoma was done in an attempt to determine the role of radiation therapy in the optimal treatment of this disease. A review of the modern literature with over 9000 cases served as a useful tool to corroborate inferences and conclusions. The present series has 155 patients (51%) treated with preoperative megavoltage external pelvic radiation with a variation in doses of less than 6%. Five-year survival estimates (79%-83%) in clinical Stage I endometrial carcinoma are similar among the several main treatment combination that are employed; they become a useless parameter for any comparison. The pelvic failure rate constitutes a more useful guideline in assessing the most adequate therapy. The pathologic grade of the tumor is the main prognosticator in endometrial carcinoma. Intimately related to the tumor grade is the depth of myometrial invasion of the carcinoma. The size of the uterus and/or its cavity carry less prognostic significance than traditionally thought. For grade I lesions, there is little error in diagnosis, few pelvic failures and excellent survival (96%); they could be approached with initial surgery and postoperative radiation reserved for selected patients. For grade 2 tumors, the error in diagnosis and the failure rate increases with an overall survival of 87%. For grade 3 tumors, the error in diagnosis and failure rates are quite high with a 5 year survival of only 70%. Preoperative radiation, especially external beam therapy, is suggested for grades 2 and 3 Stage I tumors. The use of this treatment modality yields only 3% pelvic failure and an overall 5 year survival of almost 90%.     

Prognostic factors in surgical stage I endometrial carcinoma

The prognostic impact of DNA ploidy, MIB-1 and p53 was evaluated in relation to clinical and histopathological features in surgical stage I endometrial carcinoma (n = 284) and in the histopathological endometrioid subgroup (n = 257). Tumour material from 284 consecutive patients was analysed regarding image cytometric DNA ploidy and the immunohistochemical MIB-1 and p53 expression. Twenty-four tumours relapsed. In univariate analysis, histopathological subgroup (endometrioid vs. non-endometrioid), grade, DNA ploidy and p53 were highly significant prognostic factors (p < or = 0.001). MIB-1 was also significant (p = 0.039). In the endometrioid subgroup only DNA ploidy and p53 were significant (p < 0.001). In multivariate analysis of the entire material, ploidy and histopathological subgroup retained their significance (p = 0.001, p = 0.004), whereas only ploidy was significant in the endometrioid subgroup (p = 0.001). DNA ploidy was the strongest predictor of relapse-free survival and the only independent prognostic factor in the endometrioid subgroup.     

Intraoperative I brachytherapy for high-risk stage I non-small cell lung carcinoma

Purpose: Preliminary assessment of feasibility, efficacy, acute and chronic side effects associated with permanent intraoperative placement of ¹²⁵I vicryl mesh brachytherapy in a select group of high-risk Stage I NSCLC who have undergone video-assisted thoracoscopic resection (VATR).

Methods and Materials: From January 8, 1997 to March 16, 1998, 23 patients with Stage I NSCLC at high risk for conventional surgery due to cardiopulmonary compromise underwent combined VATR and intraoperative placement of ¹²⁵I seeds embedded in vicryl mesh. Seeds embedded in vicryl suture were attached with surgical clips to a sheet of vicryl mesh, and thoracoscopically inserted over the target area (tumor bed and staple line) with nonabsorbable suture or surgical clips. A total dose of 100–120 Gy prescribed to the periphery of the target area (defined as the staple line and tumor bed with a 1-cm margin) was delivered.

Results: The mean target area covered was 48 cm² (range 40–72) and mean total activity was 22 mCi (range 17.2–28.2). The median length of postoperative stay was 7 days. The median follow-up was 11 months (range 2–20). Postoperative CT scans of the chest revealed no dislodgement of the seeds and no local recurrence in any patient.Three patients developed distant metastasis (1 died 6 months postoperatively; the other 2 are currently alive with disease). One patient developed an ipsilateral recurrence in the right lower lobe after having had a right upper lobe resection. There were 3 postoperative deaths due to medical comorbid conditions or surgical complications (1 in the immediate postoperative period). Pulmonary function testing performed 3 months after implantation revealed no significant difference between preoperative and postoperative values: mean preoperative FVC was 2.3 L (range 1.31–3.0) and postoperative FVC was 2.2 L (range 1.1–3.9), p = 0.42; mean preoperative FEV₁ was 1.2 L (range 0.71–2.2 ), and postoperative FEV₁ was 1.5 L (range 0.8–2.9), p = 0.28.

Conclusion: Review of early data suggests that intraoperative ¹²⁵I vicryl mesh brachytherapy in high-risk Stage I NSCLC is potentially effective and well tolerated, with no significant decline in measurable pulmonary function studies and no increase in postoperative complications. Longer follow-up is needed to determine ultimate local control and survival.     

Intraoperative 125I brachytherapy for high-risk stage I non-small cell lung carcinoma

Purpose: Preliminary assessment of feasibility, efficacy, acute and chronic side effects associated with permanent intraoperative placement of ¹²⁵I vicryl mesh brachytherapy in a select group of high-risk Stage I NSCLC who have undergone video-assisted thoracoscopic resection (VATR).Methods and Materials: From January 8, 1997 to March 16, 1998, 23 patients with Stage I NSCLC at high risk for conventional surgery due to cardiopulmonary compromise underwent combined VATR and intraoperative placement of ¹²⁵I seeds embedded in vicryl mesh. Seeds embedded in vicryl suture were attached with surgical clips to a sheet of vicryl mesh, and thoracoscopically inserted over the target area (tumor bed and staple line) with nonabsorbable suture or surgical clips. A total dose of 100–120 Gy prescribed to the periphery of the target area (defined as the staple line and tumor bed with a 1-cm margin) was delivered.Results: The mean target area covered was 48 cm² (range 40–72) and mean total activity was 22 mCi (range 17.2–28.2). The median length of postoperative stay was 7 days. The median follow-up was 11 months (range 2–20). Postoperative CT scans of the chest revealed no dislodgement of the seeds and no local recurrence in any patient.Three patients developed distant metastasis (1 died 6 months postoperatively; the other 2 are currently alive with disease). One patient developed an ipsilateral recurrence in the right lower lobe after having had a right upper lobe resection. There were 3 postoperative deaths due to medical comorbid conditions or surgical complications (1 in the immediate postoperative period). Pulmonary function testing performed 3 months after implantation revealed no significant difference between preoperative and postoperative values: mean preoperative FVC was 2.3 L (range 1.31–3.0) and postoperative FVC was 2.2 L (range 1.1–3.9), p = 0.42; mean preoperative FEV₁ was 1.2 L (range 0.71–2.2 ), and postoperative FEV₁ was 1.5 L (range 0.8–2.9), p = 0.28.Conclusion: Review of early data suggests that intraoperative ¹²⁵I vicryl mesh brachytherapy in high-risk Stage I NSCLC is potentially effective and well tolerated, with no significant decline in measurable pulmonary function studies and no increase in postoperative complications. Longer follow-up is needed to determine ultimate local control and survival.     

Adjuvant external beam therapy for pathologic stage I and occult stage II endometrial carcinoma

Eighty-six patients with pathologic Stage I or occult Stage II carcinoma of the endometrium and myometrial invasion and/or Grade 2 or Grade 3 histologic condition received whole-pelvis external radiation therapy (RT) after extrafascial total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-one patients received 4250 cGy in 25 daily fractions for 5 weeks (Group 1), 28 received 4500 cGy in 25 daily fractions for 5 weeks (Group 2), and 37 received 5100 cGy in 30 daily fractions for 6 weeks (Group 3). Seventeen patients had intravaginal brachytherapy after whole-pelvis RT. Local recurrence developed in two patients (2.3%) (one in Group 1 and one in Group 2). Statistical analysis showed that the depth of myometrial invasion significantly influenced survival (P = 0.016). Tumor grade, pathologic stage, whole-pelvis radiation dose, and the use of brachytherapy did not influence survival. Complications occurred in 9.5% of patients in Group 1, 24.7% in Group 2, and 40.5% in Group 3. Three patients who received brachytherapy had rectal injuries. The authors conclude that 4250 cGy in 25 fractions for 5 weeks of whole-pelvis RT appears to induce fewer complications than higher doses, and may be sufficient to prevent local recurrence in most patients who require adjuvant RT. A clinical trial is needed to determine the optimum dose-time-fractionation regimen.     

Postoperative adjuvant external-beam radiotherapy in surgical stage I endometrial carcinoma

A combined surgical and radiotherapeutic approach is widely in Stage I endometrial adenocarcinoma. The technique and timing of the radiotherapy varies from center to center. Postoperative external-beam (EB) radiotherapy has the advantage of patient selection based upon surgical findings, comprehensive treatment of the pelvic nodal and vaginal cuff areas, and elimination of the need for an intracavitary procedure. Although frequently utilized, this technique is surprisingly poorly described in the medical literature. From 1979 to 1986, 46 surgical Stage I patients received adjuvant postoperative EB therapy at Georgetown University Hospital (GUH) (Washington, DC). Indications for treatment were Grade greater than or equal to 2 and/or depth of myometrial invasion of greater than 33%. The 5-year actuarial survival was 90% with a disease-free survival of 82%. The failure rate within the irradiated field was 6.5% with a distant failure rate of 8.7%. The rate of significant long-term complications was acceptable at 6.5%. The authors conclude that postoperative EB radiotherapy is an effective adjuvant therapy with results comparable to other available radiotherapeutic techniques.     

Clinical stage I carcinoma of the testis: a review

Significant advances in the management of disseminated carcinoma of the testis have had a tremendous influence on the management of all stages of disease, including both stage I and stage II. Because the disease is so uniformly curable in advanced forms, strategies have evolved for lower stages of disease to maximize curative potential with minimization of therapeutic intervention and potential long-term side effects. This review addresses issues of diagnosis and initial clinical staging of patients with stage I carcinoma of the testis. The usefulness of biological tumor markers and the accuracy, sensitivity, and specificity of radiographic imaging modalities are emphasized. The traditional treatment of stage I seminomas and nonseminomas includes the role of both radiation therapy and retroperitoneal lymph node dissection (RPLND). Treatment results and complications of each modality are also reviewed. The importance of orchiectomy followed by meticulous surveillance, as well as a critical analysis of prognostic features of subsequent locoregional or systemic relapse in patients with stage I testis cancer, focuses attention on changing concepts of this disease. The rationale underlying improved ability to stage patients meticulously and offer therapeutic intervention when necessary following orchiectomy, constitutes the focus of present and future clinical research. Such strategies are discussed in detail.     

Prognostic factors for survival in stage I epithelial ovarian carcinoma

In a retrospective analysis prognostic factors were studied in 204 patients with primary Stage I epithelial ovarian carcinoma (borderline tumors were excluded) treated between 1975 and 1987. Only histologic grade (P = 0.01) and kind of surgery (total abdominal hysterectomy, bilateral salpingo-oophorectomy +/- omentectomy versus unilateral salpingo-oophorectomy, P = 0.02) were found to have a significant influence on survival prognosis (Cox model). All other factors (age, the International Federation of Gynecology and Obstetrics [FIGO] stage, integrity of the capsule, unilaterality versus bilaterality, and histology) were of no prognostic importance. Unilateral salpingo-oophorectomy without any additional staging reduces five-year survival probability (62% versus 84%). Therefore this kind of operation should be abandoned. Furthermore, histologic grade should be a stratification criterion in studies, which will be necessary for proving the value of adjuvant therapy in Stage I epithelial ovarian carcinoma.     

Systematic irradiation of the vaginal vault in stage I endometrial carcinoma

One hundred and twenty patients with clinical pathological stage I carcinoma of the endometrium were treated by total abdominal hysterectomy, bilateral salpingo-oophorectomy, and either pre- or postoperative intracavitary cesium insertion. External pelvic irradiation (45-50 Gy in 5 weeks) was given postoperatively in 36 cases, mainly for deep myometrial invasion. All the women have been followed for a minimum of 5 years. The overall 5-year survival rate is 86%. According to histological grading, the 5-year survival was 88, 83 and 57% for grades 1 (90 patients), 2 (23 patients) and 3 (7 patients) respectively. A total of 17 local and distant failures were observed: 10 patients had distant metastases, six patients had a pelvic failure and one had both. There was only one isolated vaginal recurrence. Depth of myometrial invasion was not a statistically significant indicator of outcome. Survival rates were comparable in pre- and postoperatively treated patients.     

Ⅰ、Ⅱ期宫颈癌卵巢转移

 本文回顾分析Ⅰ、Ⅱ期宫颈癌根治术所切除之卵巢，发现卵巢转移率为2/300(0.6%)，均为ⅡB期病人。鳞癌、腺癌各1例，转移率鳞癌为1/268例(0.37%)，腺癌为1/22例(4.55%)。两例均有盆腔淋巴结转移，其中一例腺癌有宫体浸润。资料表明卵巢转移率腺癌明显高于鳞癌。我们认为宫体浸润或/和盆腔淋巴结转移是发生卵巢转移的危险因素。在行宫颈癌根治术时保留卵巢，对鳞癌病人是较安全的，但对腺癌病人因卵巢转移的发生率较高应慎重。     

Endometrial carcinoma: two diseases?

Ninety-five patients diagnosed as having stage I endometrial carcinoma (EC) were divided into two groups, one with associated adenomatous hyperplasia (AH; group 1) and the other without (group 2). Adenomatous hyperplasia results from estrogenic stimulation of the endometrium. Therefore, patients in group 1 are considered to have an estrogen-related EC. Group 1 included 49 patients with an average age of 59; group 2 included 46 patients with an average age of 65. Review of the histologic characteristics of EC showed that group 1 tumors are better differentiated and less invasive and that their morphology is closer to the normal glandular structure of the endometrium. Group 2 tumors are less well differentiated, more often invade the myometrium, and include histologic variants such as papillary, clear cell, and anaplastic carcinoma that are dissimilar from the glandular structure of the normal endometrium. Mucinous adenocarcinomas and the presence of stromal foam cells were found to be associated with group 1 EC. Progesterone receptors (PR) were measured in a sample of 30 patients. They were present in all cases of group 1 ranging from 50 to 2,400 fmol/mg protein and absent or very low (30-190 fmol/mg protein) in group 2. All EC with stromal foam cells had high PR (380-2,400 fmol/mg protein). This study confirms that estrogen-related EC is generally a better differentiated and less aggressive tumor and suggests that there are two types of EC. The tumors not related to estrogens, which are histologically more malignant, were seen in an older age group of patients. In addition to the currently accepted methods of clinical evaluation of EC patients, defining the morphologic and biochemical characteristics of two types of EC may contribute to the management of EC, now the most prevalent cancer of the female pelvis. The patients known to be at risk for endometrial carcinoma, identifiable by abnormal hormonal manifestations (obesity, infertility, and other conditions related to hyperestrogenism) as well as those receiving exogenous estrogens are likely to develop a better differentiated and less aggressive form of neoplasia. It would be important to elaborate a system of early detection of EC in the group of elderly patients with no signs of hyperestrogenism prone to develop the less differentiated and biologically more aggressive tumors.     

Recurrent stage I endometrial carcinoma: results of treatment and prognostic factors

Recurrences of clinical Stage I endometrial carcinoma after initial treatment are rare. They are nonetheless a serious complication, uniformly associated with poor survival outcome. Between 1969-1980, 20 patients with clinical Stage I endometrial carcinoma were treated for recurrent tumor at the time of first relapse. Nonpapillary adenocarcinoma represented 70% of the primary tumors (pure adenocarcinoma, 50%; adenosquamous, 15%, clear cell, 5%) and papillary adenocarcinoma, 30%. The most common presenting symptom was vaginal bleeding, occurring in 95% of patients. The median time to recurrence after completion of primary treatment was 9.5 mo: Adenocarcinoma relapsed at a median time of 33 mo, adenosquamous, 6 mo and papillary adenocarcinoma, 4 mo. The vagina was the site of relapse in 65% of patients, the abdomen in 20%, the pelvis in 10% and the lung in 5%. Ninety-five percent of recurrences were treated with curative intent. Complications were seen in three patients, small bowel obstruction (2 pts) and vaginal vault necrosis (1 pt); however, these patients responded effectively to conservative treatment. Minimum follow-up of 4 years was available in 18 pts (90%). Actuarial 4 yr overall and NED survival was 50%, respectively, with a median survival of 39 mo to date. There have been no deaths from further recurrence of endometrial cancer beyond 39 mo. Significant prognostic factors for 4 year survival were 1) recurrence site--vagina, 82% (9/11 pts) vs extravagina, 0% (0/7 pts; median survival: 8 mo) [p = .0001]; and 2) histologic cell type--non-papillary carcinoma, 75% (9/12 pts) vs papillary adenocarcinoma, 0% (0/6 pts; median survival: 8 mo) [p = .002]. Our review suggests that: (1) Histology and site of relapse are important prognosticators of treatment outcome; (2) Long term survival may be achieved in vaginal recurrences with aggressive local treatment; and (3) There may be a role for multimodality ovarian type treatment in overall management of recurrent papillary adenocarcinoma, a cell type that appears to exhibit a tendency towards extrapelvic spread refractory to definitive loco-regional treatment.     

Postoperative chemotherapy of pathological stage I non-small cell carcinoma of the lung

Between August 1982 and February 1985, 13 patients with pathological stage I non-small cell lung cancer received postoperative chemotherapy with ACNU, ADM and 5-FU. Nine patients had squamous cell carcinoma, two adenocarcinoma, and two large cell carcinoma. All patients were alive in August, 1985, but four of them had recurrent disease. The site of recurrence was the brain in three and the contralateral lung in one. Of these four patients, three had t2n0(-) p0 squamous cell carcinoma and one t1n0(-) p1 large cell carcinoma. In a control group consisting of six squamous cell carcinoma and six adenocarcinoma, recurrence occurred in one patient with t1n0(-) p0 squamous cell carcinoma. Although the treated group had unfavorable conditions of cell type and tumor size, there was no evidence that this combination chemotherapy could control recurrence of the tumor under these conditions.     

Ⅰ期子宫内膜癌术后放疗的临床分析

目的 回顾分析265例Ⅰ期子宫内膜癌术后放疗疗效和不良反应。方法 1999—2012年进行术后放疗的Ⅰ期子宫内膜癌患者共265例。病理类型为子宫内膜样腺癌占85.3%(226例)。根据FIGO2009手术—病理分期。术后辅助放疗方式包括盆腔外照射35例(13.2%)、单纯阴道内照射107例(40.4%)和内外照射联合治疗123例(46.4%)。Kaplan-Meier法计算生存率并Logrank检验差异,Cox模型进行预后因素分析。结果 5年随访率为85.7%。5年OS、PFS、局部复发、远处转移率分别为92.8%、89.7%、4.5%、6.4%。发生3级急性放射性肠炎者仅1例(0.4%),3、4级骨髓抑制者分别为4例(1.5%)、1例(0.4%),1例(0.4%)出现3级慢性肠炎。多因素分析显示子宫下段受累是影响OS和PFS的预后因素(P=0.041、0.001),放疗前贫血是影响OS的因素(P=0.048)。 结论 子宫内膜样腺癌为主的Ⅰ期内膜癌患者进行术后辅助放疗的疗效良好,不良反应轻微,放疗前贫血和子宫下段受累是影响OS的重要因素。