Surgical-pathological Risk Factors Research Articles

Prognostic factors of 2018 FIGO stage IB-IIA cervical cancer with absence of high/ intermediate surgical-pathological risk factors.

This retrospective analysis of a real-world database of open radical hysterectomy in Japan aimed to reveal the clinicopathological findings and clinical outcomes of low-risk patients with stage IB-IIA cervical cancer. A total of 1143 stage IB1, IB2 and IIA1 (reclassified by FIGO 2018 staging system) patients with cervical cancer who underwent radical hysterectomy between January 2004 and December 2008 from the Japanese Gynecologic Oncology Group database were analyzed. Low-risk patients were defined as those without a tumor size exceeding 4cm, parametrial tumor involvement, deep (outer half) stromal invasion, lymphovascular space invasion or lymph nodal metastasis. 61.2% (772/1262) patients with stage IB1, 32.1% (229/932) with stage IB2 and 16.9% (72/294) of stage IIA1 were classified into the low-risk group. The 5-year overall survival and disease-free survival rates were 98.4 and 93.7%, respectively. Histological classification did not affect the survival rates, but stage IIA cases had significantly lower overall survival and disease-free survival (83.5 and 93.8%, respectively) than stage IB cases. The independent prognostic factors for disease-free survival were older age (≧50), histology, clinical stage and clinical stage as independent prognostic factors for overall survival. Regarding recurrence, older age, non-SCC and stage IIA1 were independent risk factors for local recurrence, but stage IIA1 was the only independent risk factor for distant metastasis. We found that stage IIA1 was the strongest risk factor for survival and recurrence of low-risk uterine cervical cancer (FIGO, 2018). In low-risk cases, stage IIA1 should be considered separately from stage IB.

The addition of chemotherapy to adjuvant radiation is associated with inferior survival outcomes in intermediate-risk HPV-negative HNSCC.

BackgroundOnly high‐risk tumors with extranodal extension (ENE) and/or positive surgical margins (PSM) benefit from adjuvant therapy (AT) with concurrent chemoradiation (CRT) compared to radiation therapy (RT) in locally advanced head and neck squamous cell carcinoma (HNSCC). Optimal treatment for intermediate‐risk tumors remains controversial. We categorized patients based on their surgical pathologic risk factors and described AT treatment patterns and associated survival outcomes.MethodsPatients were identified from CHANCE, a population‐based study, and risk was classified based on surgical pathology review. High‐risk patients (n = 204) required ENE and/or PSM. Intermediate‐risk (n = 186) patients had pathological T3/T4 disease, perineural invasion (PNI), lymphovascular invasion (LVI), or positive lymph nodes without ENE. Low‐risk patients (n = 226) had none of these features.ResultsWe identified 616 HPV‐negative HNSCC patients who received primary surgical resection with neck dissection. High‐risk patients receiving AT had favorable OS (HR 0.50, p = 0.013) which was significantly improved with the addition of chemotherapy compared to RT alone (HR 0.47, p = 0.021). When stratified by node status, the survival benefit of AT in high‐risk patients persisted only among those who were node‐positive (HR: 0.17, p < 0.0005). On the contrary, intermediate‐risk patients did not benefit from AT (HR: 1.26, p = 0.380) and the addition of chemotherapy was associated with significantly worse OS compared to RT (HR: 1.76, p = 0.046).ConclusionIn high‐risk patients, adjuvant chemoradiotherapy improved OS compared to RT alone. The greatest benefit was in node‐positive cases. In intermediate‐risk patients, the addition of chemotherapy to RT increased mortality risk and therefore should only be used cautiously in these patients.

Prognostic Assessment of Cervical Cancer Patients by Clinical Staging and Surgical-Pathological Factor: A Support Vector Machine-Based Approach.

Introduction: The International Federation of Gynecology and Obstetrics (FIGO) staging system is considered the most powerful prognostic factor in patients with cervical cancer. In addition, other surgical-pathological risk factors have been demonstrated to have significance in predicting the prognosis of patients. Therefore, the purpose of this study was to investigate the effects of the FIGO staging system and surgical-pathological risk factors on the prognosis of cervical cancer patients.Methods: A retrospective study was performed on patients diagnosed with cervical cancer at FIGO stage IB1–IIA2. Kaplan–Meier, Cox proportional hazards regression analysis and the support vector machine (SVM) algorithm were used to assess and validate the high-risk factors related to recurrence and death.Results: A total of 647 patients were included. Kaplan-Meier analysis showed that five high-risk factors, including FIGO stage, status of pelvic lymph node, parametrial involvement, tumor size, and depth of cervical cancer, had a significant effect on the prognosis of patients. In multivariate analysis, pelvic lymph node metastasis (hazard ratio [HR] 2.415, 95% confidence interval [CI] 1.471–3.965), parametrial involvement (HR 2.740, 95% CI 1.092–6.872) and >2/3 depth of cervical invasion (HR 2.263, 95% CI 1.045–4.902) were three independent risk factors of disease-free survival. Pelvic lymph node metastasis (HR 3.855, 95% CI 2.125–6.991) and parametrial involvement (HR 3.871, 95% CI 1.375–10.900) were two independent risk factors for overall survival. When all five high-risk factors were assembled and used for classification prediction through SVM, it achieved the highest prediction accuracy of recurrence (accuracy = 69.1%). The highest prediction accuracy for survival was 94.3% when only using the two independent predictors (the pathological status of lymph nodes and parametrium involvement) by SVM classifiers. Among the 13 groups of intermediate-risk factor, the combination of tumor size, histology and grade of differentiation was more accurate in predicting prognosis than the intermediate-risk factors in the Sedlis criteria (recurrence: 86.8% vs. 60.0%; death: 92.0% vs. 71.6%).Conclusions: The combination of FIGO stage and surgical-pathological risk factors can further enhance the prediction accuracy of the prognosis in patients with early-stage cervical cancer. Histology and grade of differentiation can further improve the prediction accuracy of intermediate-risk factors in the Sedlis criteria.

Populational trends and outcomes of postoperative radiotherapy for high-risk early-stage cervical cancer with lymph node metastasis: concurrent chemo-radiotherapy versus radiotherapy alone

Pelvic lymph node metastasis carries the highest impact on decreased survival among surgical-pathological risk factors for early-stage cervical cancer. Although concurrent administration of chemotherapy during postoperative radiotherapy is the current standard treatment for surgically treated high-risk early-stage cervical cancer, its effectiveness specific to node-positive disease has not been completely studied. To examine the association between the use of concurrent chemotherapy and survival in women with early-stage cervical cancer and nodal metastasis receiving adjuvant radiotherapy. This is a population-based cohort study using the Surveillance, Epidemiology, and End Results Program from 1988 to 2016. Women with stage T1-2 cervical cancer with pelvic lymph node metastasis who underwent hysterectomy and received postoperative radiotherapy were examined. Trends, characteristics, and overall survival were compared between women who received postoperative radiotherapy alone (n= 729) or in combination with concurrent chemo-radiotherapy (n= 1809). Propensity score-based inverse probability of treatment weighting was used to account for the effect of measured covariates on treatment selection. Among 2538 women, there was a marked increase in the use of concurrent chemotherapy from 1997 to 2000 (20.7% to 78.5%, P= .052), followed by a more gradual rise through 2016 (88.3%, P < .001). In a multivariable model, women with non-squamous cell carcinomas and those diagnosed more recently were more likely to receive concurrent chemo-radiotherapy, whereas older women were less likely to receive concurrent chemo-radiotherapy (all, P < .05). At the population level, the 5-year overall survival rates remained unchanged (annual percent change for 1997-2012: -0.1; 95% confidence interval, -1.2 to 1.0; P= .776). In a propensity score weighted cohort, women who received concurrent chemo-radiotherapy had a 5-year overall survival rate similar to women treated with radiotherapy alone (73.1% vs 73.6%; hazard ratio, 1.004; 95% confidence interval, 0.887-1.136; P= .955). Significant differences were also not seen in older women, nonsquamous types, stage T2 disease, and multiple node metastases (all, P > .05). Despite the marked increase in the use of concurrent chemo-radiotherapy for women with early-stage cervical cancer and nodalmetastases, there was no association between use of concurrent chemotherapy during postoperative radiotherapy and improved survival.

Long-term outcomes of postoperative taxane/platinum chemotherapy for early stage cervical cancer: a retrospective study.

Taxane/platinum (TP)-based combination chemotherapy is standard for the treatment of metastatic or recurrent cervical cancer. The aim of this study was to investigate the efficacy of postoperative TP therapy in early stage cervical cancer. A retrospective review of patients with FIGO IB-IIB stage cervical cancer who were treated with radical hysterectomy and displayed surgical-pathological risk factors was performed. 122 patients were identified between 2003 and 2012. Survival was analyzed by Kaplan-Meier method and compared by the log-rank test. The Cox proportional hazards model was used to investigate predictors of survival. The median follow-up period was 82.4months. The postoperative adjuvant therapy was TP in 82 (67.2%) patients, other chemotherapies in 10 (8.2%), radiotherapy (RT) in 25 (20.5%), and no further therapy (NFT) in 5 (4.1%). Survival was analyzed using 4 subgroups according to the postoperative adjuvant therapy. The estimated 5-year overall survival was 95.1% in the TP group, 90.0% in the other chemotherapy group, 78.9% in the RT group, and 100% in the NFT group. No significant difference of survival was observed in the subgroups. However, when analyzing only patients who displayed high-risk factors, non-TP adjuvant therapy (including RT and other chemotherapies) was independently associated with shorter survival on multivariate analysis. In the TP group, multivariate analysis revealed that a positive surgical margin was a significant predictor of shorter survival. Postoperative TP is effective in patients with surgically treated early stage cervical cancer. In these populations, a positive surgical margin could be associated with poor prognosis.

Oncologic outcomes of adjuvant chemotherapy alone after radical surgery for stage IB-IIA cervical cancer patients.

ObjectiveTo evaluate the oncologic outcomes of adjuvant chemotherapy (CT) alone after radical surgery.MethodsWe retrospectively reviewed the medical records of patients who underwent type C radical hysterectomy and pelvic lymphadenectomy with or without paraaortic lymphadenectomy for stage IB–IIA cervical cancer from March 2006 to December 2014 at 2 academic medical centers in Korea. Adjuvant CT alone for patients who met the Sedlis criteria or had lymph node (LN) involvement. Chemotherapeutic regimens consisted of either platinum alone or platinum-based combination.ResultsA total of 101 consecutive patients were included in the analysis. The median age was 46.0 years (range, 23–73). Seventy-four patients (73.3%) were clinically staged as IB1; 23 and 4 patients as IB2 and IIA, respectively. The median number of retrieved pelvic and paraaortic LNs (PALNs) were 55.0 (range, 16–101) and 10.0 (range, 2–30), respectively. LN involvement was observed in 25 patients (24.8%). After the median follow-up of 65 months, 14 patients (13.9%) developed disease recurrence. In all patients, the estimated 3-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate were 90.7% and 90.6%, respectively. In patients who met the Sedlis criteria, the 3-year DFS and 5-year OS rates were 94.6% and 90.6%, respectively. Patients with LN metastasis showed a 3-year DFS rate of 79.4% and a 5-year OS rate of 90.6%.ConclusionAdjuvant CT alone could be reasonable option for patients with surgical-pathologic risk factors after radical surgery in stage IB–IIA cervical cancer.

Risk stratification models for para-aortic lymph node metastasis and recurrence in stage IB-IIB cervical cancer.

ObjectiveTo examine the surgical-pathological predictors of para-aortic lymph node (PAN) metastasis at radical hysterectomy, and for PAN recurrence among women who did not undergo PAN dissection at radical hysterectomy.MethodsThis is a retrospective analysis of a nation-wide cohort study of surgically-treated stage IB–IIB cervical cancer (n=5,620). Multivariate models were used to identify independent surgical-pathological predictors for PAN metastasis/recurrence.ResultsThere were 120 (2.1%) cases of PAN metastasis at surgery with parametrial involvement (adjusted odds ratio [aOR]=1.65), deep stromal invasion (aOR=2.61), ovarian metastasis (aOR=3.10), and pelvic nodal metastasis (single-node aOR=5.39 and multiple-node aOR=33.5, respectively) being independent risk factors (all, p<0.05). Without any risk factors, the incidence of PAN metastasis was 0.9%, while women exhibiting certain risk factor patterns (>20% of the study population) had PAN metastasis incidences of ≥4%. Among 4,663 clinically PAN-negative cases at surgery, PAN recurrence was seen in 195 (4.2%) cases that was significantly higher than histologically PAN-negative cases (2.5%, p=0.046). In clinically PAN-negative cases, parametrial involvement (adjusted hazard ratio [aHR]=1.67), lympho-vascular space invasion (aHR=1.95), ovarian metastasis (aHR=2.60), and pelvic lymph node metastasis (single-node aHR=2.49 and multiple-node aHR=8.11, respectively) were independently associated with increased risk of PAN recurrence (all, p<0.05). Without any risk factors, 5-year PAN recurrence risk was 0.8%; however, women demonstrating certain risk factor patterns (>15% of the clinically PAN-negative population) had 5-year PAN recurrence risks being ≥8%.ConclusionSurgical-pathological risk factors proposed in this study will be useful to identify women with increased risk of PAN metastasis/recurrence.

A matter of margins: Surgical-pathologic risk factors for recurrence in extramammary Paget’s disease

Objective: To determine surgical and pathologic variables associated with recurrence in extramammary Paget’s disease. This is the largest published series comparing wide local excision (WLE) to Mohs micrographic surgery (MMS).

Effectiveness of cervical cancer therapy using neoadjuvant chemotherapy in combination with radical surgery: a meta-analysis

Background: Cervical cancer is the fourth of most common cancers, and also the fourth cause of women death in the world. Neoadjuvant chemotherapy (NACT) combined with conventional radical surgery (RS) has been proposed to be able to eradicate the micro metastasis for advanced cervical tumors so that improve the survival of cancer patients. However, the effectiveness of combined treatment of both NACT and RS is still a debate. Results from different studies are usually inconsistent, even contradictory. Methods: To evaluate the advantage of the combination of NACT and RS over RS alone for cervical cancer, we performed a meta-analysis, which involved eight case-control studies. Two-year and 5-year disease-free survival (DFS) and overall survival (OS) were compared with stratification analysis in each group with regard to the surgical-pathologic high risk factors including lymph node metastasis, positive surgical margin, parametric infiltration, lymphovascular invasion, cervical stromal depth and positive pelvic nodes. Results: Our study showed that cervical cancer patients with additive NACT treatment may have no additional benefit for the long-term OS and DFS than RS alone group [2-year OS: odds ratios (ORs) =1.008; 95% confidence intervals (CIs), 0.832–1.220; P=0.937; 5-year OS: OR =1.054; 95% CI, 0.860–1.292; P=0.913; 2-year DFS: OR =1.015; 95% CI, 0.853–1.207; P=0.870; 5-year DFS: OR =1.001; 95% CI, 0.816–1.228; P=0.992]. Further subgroup meta-analysis of adjuvant therapy and stratification adjustment with six surgical–pathologic risk factors also drew the same conclusion. Conclusions: These results suggested that NACT might not be effective enough to elongate patients survival as been reported by some studies, further confirmation needs to be done by more profound analyses.

Can pelvic lymphadenectomy be omitted in patients with stage IA2, IB1, and IIA1 squamous cell cervical cancer?

PurposeThis study aimed to identify the surgical-pathologic risk factors of lymph node metastasis (LNM) in patients with early stage squamous cell cervical cancer and to evaluate the potential efficacy of omitting pelvic lymphadenectomy.MethodsA total of 276 patients with stage IA2, IB1, and IIA1 squamous cell cervical cancer receiving primary radical hysterectomy with pelvic lymphadenectomy were included in this study.ResultsThe incidences of LNM in patients with stage IA2, IB1, and IIA1 squamous cell cervical cancer were 0 % (0/8), 17.4 % (36/207), and 29.5 % (18/61), respectively. The most common location of LNM was the obturator lymph node. Human papilloma virus 16 subtype was the most common infection in early stage squamous cell cervical cancer. Univariate analysis revealed that squamous cell carcinoma antigen (SCCAg) greater than 1.5 μg/L (p < 0.001), tumor size greater than 2 cm (p < 0.001), tumor size greater than 3 cm (p < 0.001), depth of stromal invasion (p < 0.001) and lymphovascular invasion (p < 0.001) were associated with LNM. Logistic regression analysis revealed that depth of stromal invasion {model 1 [p = 0.006; odds ratio (OR) 2.161; 95 % confidence interval (CI) 1.251–3.734], model 2 [p = 0.002; OR 2.344; 95 % CI 1.337–3.989]}, lymphovascular invasion [model 1 (p = 0.004; OR 2.967; 95 % CI 1.411–6.237), model 2 (p = 0.004; OR 2.978; 95 % CI 1.421–6.243)], and SCCAg greater than 1.5 μg/L [model 1 (p = 0.023; OR 2.431; 95 % CI 1.129–5.235), model 2 (p = 0.024; OR 2.418; 95 % CI 1.125–5.194)] were independently associated with LNM.ConclusionsPelvic lymphadenectomy may be omitted in patients with SCCAg lower than 1.5 μg/L, superficial stromal invasion and without lymphovascular invasion in stage IA2, IB1, IIA1 squamous cell cervical cancer.

Development and validation of a surgical-pathologic staging and scoring system for cervical cancer.

BackgroundMost cervical cancer patients worldwide receive surgical treatments, and yet the current International Federation of Gynecology and Obstetrics (FIGO) staging system do not consider surgical-pathologic data. We propose a more comprehensive and prognostically valuable surgical-pathologic staging and scoring system (SPSs).MethodsRecords from 4,220 eligible cervical cancer cases (Cohort 1) were screened for surgical-pathologic risk factors. We constructed a surgical-pathologic staging and SPSs, which was subsequently validated in a prospective study of 1,104 cervical cancer patients (Cohort 2).ResultsIn Cohort 1, seven independent risk factors were associated with patient outcome: lymph node metastasis (LNM), parametrial involvement, histological type, grade, tumor size, stromal invasion, and lymph-vascular space invasion (LVSI). The FIGO staging system was revised and expanded into a surgical-pathologic staging system by including additional criteria of LNM, stromal invasion, and LVSI. LNM was subdivided into three categories based on number and location of metastases. Inclusion of all seven prognostic risk factors improves practical applicability. Patients were stratified into three SPSs risk categories: zero-, low-, and high-score with scores of 0, 1 to 3, and ≥4 (P=1.08E-45; P=6.15E-55). In Cohort 2, 5-year overall survival (OS) and disease-free survival (DFS) outcomes decreased with increased SPSs scores (P=9.04E-15; P=3.23E-16), validating the approach. Surgical-pathologic staging and SPSs show greater homogeneity and discriminatory utility than FIGO staging.ConclusionsSurgical-pathologic staging and SPSs improve characterization of tumor severity and disease invasion, which may more accurately predict outcome and guide postoperative therapy.

Utility of risk-weighted surgical pathological risk factors in predicting survival outcomes among women with vulvar cancer: A population-based study

Utility of risk-weighted surgical pathological risk factors in predicting survival outcomes among women with vulvar cancer: A population-based study

Utility of risk-weighted surgical-pathological factors in early-stage cervical cancer

Objective: Surgical-pathological risk factors have been used in determining the indications for adjuvant treatment and the survival of surgically treated early- stage cervical cancer. We further evaluated the surgical-pathological risk factors by weighting the magnitude of significance of multiple risk factors correlating to survival and treatment response.

Surgical-Pathologic Risk Factors and Immunohistochemical Markers of Pelvic Lymph Node Metastasis in Stage IB1 Cervical Cancer

: This study aimed to identify the surgical-pathologic risk factors and immunohistochemical markers of pelvic lymph node metastasis in stage IB1 cervical cancer. : A retrospective review of patients with stage IB1 cervical cancer who underwent radical abdominal hysterectomy, lymph node dissection, and immunohistochemical staining for p53, bcl-2, and Ki-67 was performed. : A total of 29 patients with complete clinical data and pathology tissue blocks are the subjects of this study. Of these patients, 20 (69%) had squamous cell carcinoma, 8 (28%) had adenocarcinoma, and 1 (3%) adenosquamous carcinoma. The median tumor diameter as measured in the pathology laboratory was 2 cm. The median number of lymph nodes removed was 24. Four (14%) patients had positive lymph nodes. Lymphovascular invasion was noted in 10 (34%). None of the 19 patients without lymphovascular invasion had lymph node involvement. Of 29 patients, 2 (7%) had parametrial involvement. There was a statistically significant correlation between tumor diameter and depth of invasion (r = 0.43, p = .02), and between lymphovascular invasion and positive lymph nodes (r = 0.55, p = .0019). The Ki-67 immunostaining index was higher for patients with lymphovascular invasion and/or positive lymph nodes (p = .008 and p = .028, respectively). There was no association between p53 or bcl-2 expression and lymphovascular invasion or lymph node metastasis. : Lymph node metastasis (14 %) and parametrial involvement (7%) occurred only in patients with lymphovascular invasion and/or large tumor size. The Ki-67 staining index is associated with lymphovascular invasion and lymph node metastasis.

Does fluid hysteroscopy increase the stage or worsen the prognosis in patients with endometrial cancer?: A randomized controlled trial

Objective: To determine whether fluid hysteroscopic directed biopsies, in patients with endometrial cancer upstages the tumor and worsens the prognosis. Study design: Between January 1996 and September 2001, a total of 62 consecutive patients with endometrial cancer, treated at our institution, were randomized 3:2 to have or not to have a fluid hysteroscopic biopsy just prior to surgery. A total of 38 patients underwent a hysteroscopy after the induction of anesthesia. All patients had pelvic washings performed, followed by a hysterectomy, bilateral salpingooforectomy and pelvic +/− para-aortic lymph node dissections. Only stages I and II endometrioid type tumors or stage IIIa, secondary to positive pelvic washings, were included in the study. Eight patients in the hysteroscopy group and four patients in the control group were excluded for various reasons. Patients received post-operative radiation therapy depending on the surgical–pathological risk factors. The median follow up was 34 months. Fisher’s Exact Test was performed to compare differences between the hysteroscopic ( n=30) and the control ( n=20) groups. Results: We found three patients (10%) with positive washings in the hysteroscopic group compared to one (5%) among the controls ( P=0.64), with a statistical power of <20%. If the differences would persist, we would need 588 patients in each arm to obtain a power of 80%, and reach definitive conclusions. The Odds Ratio (OR) of performing a hysteroscopy and upstaging the tumor in this study was: 2.1 95% CI (0.20–21.09). Prognostic variables were compared between both groups and no differences were observed. All patients but one (dead due to intercurrent disease), were alive and with no evidence of disease at the completion of the study. Conclusions: Fluid hysteroscopy and directed biopsies may have a small risk of upstaging early endometrial cancers, but does not seem to influence prognosis.

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

International Journal of Gynecology & ObstetricsVolume 36, Issue 4 p. 352-353 Citations from the literature oncology Relationship between surgical-pathological risk factors and outcome in clinical stage I and II carcinoma of the endometrium: A Gynecologic Oncology Group study CP Morrow, CP MorrowSearch for more papers by this authorBN Bundy, BN BundySearch for more papers by this authorRJ Kurman, RJ KurmanSearch for more papers by this authorWT Creasman, WT CreasmanSearch for more papers by this authorP Heller, P HellerSearch for more papers by this authorHD Homesley, HD HomesleySearch for more papers by this authorJE Graham, JE GrahamSearch for more papers by this author CP Morrow, CP MorrowSearch for more papers by this authorBN Bundy, BN BundySearch for more papers by this authorRJ Kurman, RJ KurmanSearch for more papers by this authorWT Creasman, WT CreasmanSearch for more papers by this authorP Heller, P HellerSearch for more papers by this authorHD Homesley, HD HomesleySearch for more papers by this authorJE Graham, JE GrahamSearch for more papers by this author First published: December 1991 https://doi.org/10.1016/0020-7292(91)90520-FAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume36, Issue4December 1991Pages 352-353 RelatedInformation

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. These data seem to implicate malignant cytology as a serious adverse finding, especially with respect to the risk for regional/distant and abdominal failure.