SUVmax of 18FDG PET/CT as a predictor of high-risk endometrial cancer patients.

OBJECTIVE: To evaluate SUVmax in the assessment of endometrial cancer preoperatively with particular focus on myometrial invasion (MI), cervical invasion (CI), FIGO stage, risk-stratification and lymph node metastases (LNM). METHODS: A total of 268 women with endometrial cancer or atypical endometrial hyperplasia underwent FDG PET/CT imaging before surgical treatment. SUVmax of the primary tumour was compared with histological prognostic factors. RESULTS: SUVmax was significantly higher in patients with high FIGO stages (p<0.0001), deep MI (p=0.002), CI (p=0.04), LNM (p=0.04) and high risk tumours (p=0.003). Linear regression found that SUVmax was dependent of MI (p=0.001, 95% CI 2.863-11.098), CI (p=0.001, 95% CI 2.896-11.499), risk (p=0.004, 95% CI 0.077-0.397), LNM (p=0.04, 95% CI 0.011-0.482) and FIGO stage (p<0.0001, 95% CI 0.158-0.473). CONCLUSIONS: Preoperative PET/CT scanning and SUVmax measurements of the primary tumour may provide additional clinical and prognostic information about MI, CI, LNM and high risk disease in patients with endometrial cancer and allow for individualization of patient care. However, the sensitivity and specificity of the SUVmax in staging endometrial cancer is not high enough to reliably replace surgical staging.

MRI, PET/CT and ultrasound in the preoperative staging of endometrial cancer - a multicenter prospective comparative study.

OBJECTIVES: The aim of this prospective multicenter study was to evaluate and compare the diagnostic performance of PET/CT, MRI and transvaginal two-dimensional ultrasound (2DUS) in the preoperative assessment of endometrial cancer (EC). METHODS: 318 consecutive women with EC were included when referred to three Danish tertiary gynecological centers for surgical treatment. Preoperatively they were PET/CT-, MRI-, and 2DUS scanned. The imaging results were compared to the final pathological findings. This study was approved by the National Committee on Health Research Ethics. RESULTS: For predicting myometrial invasion, we found sensitivity, specificity, PPV, NPV, and accuracy for PET/CT to be 93%, 49%, 41%, 95% and 61%, for MRI to be 87%, 57%, 44%, 92%, and 66% and for 2DUS to be 71%, 72%, 51%, 86% and 72%. For predicting cervical invasion, the values were 43%, 94%, 69%, 85% and 83%, respectively, for PET/CT, 33%, 95%, 60%, 85%, and 82%, respectively, for MRI, and 29%, 92%, 48%, 82% and 78% for 2DUS. Finally, for lymph node metastases, the values were 74%, 93%, 59%, 96%, and 91% for PET/CT and 59%, 93%, 40%, 97% and 90% for MRI. When comparing the diagnostic performance we found PET/CT, MRI and 2DUS to be comparable in predicting myometrial invasion. For cervical invasion and lymph node metastases, however, PET/CT was the best. CONCLUSIONS: None of the modalities can yet replace surgical staging. However, they all contributed to important knowledge and were, furthermore, able to upstage low-risk patients who would not have been recommended lymph node resection based on histology and grade alone.

Diagnostic accuracy of risk of malignancy index in predicting complete tumor removal at primary debulking surgery for ovarian cancer patients.

Ovarian cancer patients in whom complete tumor removal is impossible with primary debulking surgery (PDS) may benefit from neoadjuvant chemotherapy and interval debulking surgery. However, the task of performing a pre-operative evaluation of the feasibility of PDS is difficult. We aimed to investigate whether the risk of malignancy index (RMI) was a useful marker for this evaluation. RMI and surgical outcome were investigated in 164 patients, 49 of whom had no residual tumor after PDS. The receiver operating characteristic curve showed an area under the curve of 0.72 (confidence interval: 0.64-0.80). The possibility of complete tumor removal decreased with increasing RMI and there was a tendency towards higher RMI in patients with residual tumor after PDS, but no single cut-off value of RMI produced useful clinical predictive values. In conclusion, RMI alone is not an optimal method to determine whether complete tumor removal is possible with PDS.

HE4 and CA125 levels in the preoperative assessment of endometrial cancer patients: a prospective multicenter study (ENDOMET).

OBJECTIVE: To evaluate whether human epididymis protein 4 (HE4) and CA125 correlate with known high-risk prognostic factors for endometrial cancer. DESIGN: Prospective multicenter study. SETTING: Three Danish tertiary gynecological oncology centers. POPULATION: A total of 352 patients with endometrial cancer and atypical endometrial hyperplasia consecutively referred between 1 September 2009 and 1 January 2012. METHODS: Preoperative blood samples were obtained from all patients. Biomarker levels were correlated with pathological characteristics of hysterectomy specimens. MAIN OUTCOME MEASURES: FIGO stage, depth of myometrial invasion, cervical involvement, lymph node metastases, and histological type and grade of tumor. RESULTS: We found that both HE4 and CA125 were significantly positively correlated with histological grade (HE4: p = 0.002 and CA125: p = 0.027), lymph node metastases (HE4: p = 0.013 and CA125: p < 0.0001), myometrial invasion (p < 0.0001) and cervical involvement (p < 0.0001). Furthermore, a significant increase was found with increasing FIGO stage for both markers (p < 0.0001). In a combined index including age, the diagnostic value increases. Area under the receiver operating characteristics curves were higher for the index compared with the markers individually for all our endpoints. The calculated plots for the combined index may assist gynecologists in predicting the risk of deep myometrial invasion, cervical involvement and lymph node metastases. The analyses emphasize that the combined markers should be used in the prediction of prognostic factors. CONCLUSION: This study confirmed that the markers are significantly elevated in patients with prognostic high-risk factors and may, therefore, be used as an additional tool in combination with imaging and clinical information when planning the treatment of endometrial cancer patients.

Centralized treatment of advanced stages of ovarian cancer improves survival: a nationwide Danish survey.

OBJECTIVE: This retrospective, nationwide, observational study was designed to compare treatment in tertiary referral centers vs. regional hospitals on overall survival for patients with stage IIIC and IV ovarian cancer. MATERIAL AND METHODS: The study took place in all gynecological departments in Denmark, involving a total of 1,160 patients with stage IIIC or IV ovarian cancer. Data were extracted for 2,024 patients with all stages of ovarian cancer recorded in the Danish Gynecological Cancer Database between 1 January 2005 and 31 December 2008. The main outcome measure was overall survival. RESULTS: No difference was found between tertiary centers and regional hospitals with regard to age, body mass index, American Society of Anesthesiologists score or comorbidity. Patients in regional hospitals had poorer Eastern Cooperative Oncology Group performance status, i.e.1.0 vs. 2.0 (p= 0.005). Patients in referral centers presented more often with stage IIIC and IV disease, i.e. 59.7 vs. 51.7% (p < 0.001). Patients with stage IIIC and IV disease in regional vs. tertiary hospitals had a higher rate of primary cytoreductive surgery, i.e. 89.5 vs. 82.5% (p= 0.004), a poorer rate of complete cytoreductive surgery following primary cytoreductive surgery, i.e. 13.9 vs. 25.2% (p < 0.001), a lower rate of neoadjuvant chemotherapy, i.e. 5.5 vs. 13.4% (p < 0.001), and more often underwent acute surgery, i.e. 17.0 vs. 9.2% (p < 0.001). Patients treated in referral centers had better overall survival (p= 0.021). Treatment in a referral center was an independent prognostic factor for overall survival hazard ratio, 0.83 (confidence interval 0.70-0.98). CONCLUSION: Patients with stage IIIC and IV ovarian cancer benefit from treatment in a tertiary referral center.

Neoadjuvant chemotherapy as ovarian cancer treatment: ever more used with major regional differences.

INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval debulking surgery. The aim of this study was to investigate the use of NACT in Denmark in regard to increased use and regional differences. MATERIAL AND METHODS: Stage IIIC and IV ovarian cancer patients treated in the five Danish tertiary referral centres in the 2005-2010-period were included. The study is based on validated data from The Danish Gynaecological Cancer Database. RESULTS: Of the 1,367 eligible patients 1,069 were treated with PDS and 298 with NACT. In 2005-2007, 11% of patients were treated with NACT. In 2008-2010, this percentage had risen to 30% (p < 0.00001). Between the five referral centres, the use of NACT ranged from 6% to 41% in 2005-2010 (p < 0.00001); from 1 % to 31% in 2005-2007 (p < 0.00001); from 10% to 48% in 2008-2010 (p < 0.00001) and from 9% to 48% in 2010 (p < 0.0008). Patients treated with NACT were significantly older, had inferior ASA scores and Eastern Cooperative Oncology Group performance status compared with the patients from the PDS group. There was no difference between treatments in regard to body mass index, stage IV disease or patients with no co-morbidity. CONCLUSION: The use of NACT as first-line treatment tripled from 2005-2010, but the regional variability was large which calls for a uniform agreement on treatment principles and evaluation. FUNDING: This study was financially supported by grants from The Copenhagen University Hospital Research Foundation, Manufacturer Einar Willumsens Memorial Trust, The Capital Region of Denmark Research Foundation, The Arvid Nilsson Foundation, The King Christian X Foundation, The Dagmar Marshall Foundation, The Danish Research Foundation, and The Hans and Nora Buchard Foundation. TRIAL REGISTRATION: not relevant.