Clinical outcome of patients with endometrial cancer in Norway after omission of radiotherapy and the evaluation of L1CAM as a prognostic factor

Endometrial cancer (EC) is the most common gynecological malignancy. Surgery is the treatment of choice. The risk of relapse after surgery is related to clinicopathologic risk factors. Novel markers are needed for better prediction of individual risk of recurrence. The aims of this thesis were to evaluate L1CAM as a prognostic marker, to evaluate the clinical outcome for women with high-risk EC receiving adjuvant chemotherapy without radiation and further to evaluate the outcome for radionaïve patients with locoregional recurrence given radiotherapy as salvage therapy. L1CAM expression was related to more distant recurrences and poorer survival but failed to be of additional clinical help in our cohort of patients. Women in high risk of relapse had acceptable vaginal/pelvic control rates after adjuvant chemotherapy only, but the risk of distant recurrences is still high, indicating a need for better treatment to this group. For radionaïve EC patients with locoregional recurrence, the risk of a second relapse after salvage radiotherapy was low in the low- and intermediate-risk groups but high in the high-risk groups, mostly due to distant recurrences

Clinical Outcome of Patients with High-Risk Endometrial Carcinoma after Treatment with Chemotherapy only

Objectives: Adjuvant treatment of high-risk endometrial cancer (EC) is still controversial. Several studies have tried to clarify the best treatment strategy, and guidelines have been made, but no study to date has shown a survival benefit for radiation over chemotherapy. We aimed to evaluate the outcome of high-risk EC patients treated with adjuvant chemotherapy only in a population where the routine administration of adjuvant radiotherapy was omitted. Methods: This is a retrospective study including 230 EC patients with International Federation of Gynecology and Obstetrics stage I type II, stage Ib type I/G3, stage II, and IIIc treated at Oslo University Hospital between 2005 and 2012. Standard treatment was hysterectomy, bilateral salpingo-oophorectomy and at least pelvic lymphadenectomy followed by adjuvant chemotherapy. Results: Of the 230 high-risk patients, standard treatment was given to 146 patients (63.5%): 60 patients in stage I, 10 patients in stage II, and 76 patients in stage IIIc. Only 10% of patients with stage I disease relapsed, with 3.3% locoregional relapses and 6.7% distant relapses. Recurrence rate in stage IIIc was 39.5%, with 7.9% isolated vaginal and 31.6% distant relapses. The 3-year disease-free survival was 92% for stage I, 80% for stage II, and 60% for stage IIIc disease. In the total population, 55 patients had International Federation of Gynecology and Obstetrics stage Ia, 43 Ib, 42 stage II, and 90 stage IIIc disease. Recurrence rate in the total population was 29.6%, with 9.6% isolated vaginal recurrences, 1.7% recurrences located in the pelvis, and 18.3% distant recurrences. Conclusions: Patients with high-risk EC have acceptable vaginal/pelvic control rates after adjuvant chemotherapy. However, prognosis remains poor for patients with stage IIIc disease, also after chemotherapy

L1CAM as a prognostic marker in stage I endometrial cancer: a validation study

Background L1 cell adhesion molecule (L1CAM) overexpression has been reported to be strongly associated with poor prognosis in early stage endometrial cancer (EC). We aimed at the validation of L1CAM as a marker of poor prognosis in an independent study population. Methods Patients with endometrioid EC FIGO stage I, were treated at Oslo University Hospital between 2005 and 2012. L1CAM expression was detected by immunohistochemistry with >10 % L1CAM staining defined as positive. Risks of relapse and death were estimated as hazard ratios (HRs) with 95 % confidence intervals (95 % CI). Results Of 450 patients, 388 (86 %) were evaluable for L1CAM expression and 35 (9 %) were L1CAM positive. After follow-up for a median time of 4.8 years (0.1–8.8), 33 (8 %) patients had recurred. 6/35 (17 %) L1CAM positive patients relapsed compared to 27/353 (8 %) L1CAM-negative patients. There were 7 (20 %) deaths in the L1CAM positive group, and 34 (10 %) in the negative group. In multivariate analysis, controlled for age and FIGO stage, L1CAM positivity was not significantly associated with the risk of relapse (HR 2.08, 95 % CI: 0.85–5.10, p = 0.11) or death of all-cause (HR 1.81, 95 % CI: 0.79–4.11, p = 0.16). In patients who were not treated with chemotherapy, L1CAM was significantly associated with risk of relapse (HR 2.9; 95 % CI: 1.08–7.56; p = 0.04). Conclusion Our report confirms that L1CAM is associated with a more aggressive tumortype and more distant relapses. The overall recurrence rate in this population was low as were the absolute differences between L1CAM positive and negative patients. In this independent study sample, L1CAM failed to be a clinically relevant marker of poor prognosis in stage I endometrioid endometrial carcinoma

Salvage radiation for pelvic relapse after surgically treated endometrial cancer

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome

Salvage Radiation for Pelvic Relapse after Surgically Treated Endometrial Cancer

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome

Salvage radiation for pelvic relapse after surgically treated endometrial cancer

(1) Background: This study evaluated the clinical outcome after salvage radiotherapy for first pelvic relapse after endometrial cancer (EC). (2) Methods: This multicenter retrospective study included EC patients with first central pelvic relapse without lymph node involvement treated with curative intent. Progression-free (PFS) and overall survival (OS) were calculated with the Kaplan–Meier method and possible predictive factors for risk of relapse and mortality were identified using the Cox model. (3) Results: We included 139 patients with median EQD2 (Equivalent Dose in 2 Gy fractions) to the clinical target volume of 70.0 Gy. During follow up of median 6.66 years, 39.6% patients developed a second relapse. Risk group classification at primary diagnosis based on histology, grading and FIGO stage and how the pelvic tumor boost was administered were independently associated with PFS and OS. Five-year OS was 68% (95% CI (59–75)) for the whole cohort. Five-year OS was 88% (95% CI (75–94)), 72% (95% CI (55–84)) and 38% (95% CI (15–60)) for the stage I low-, intermediate- and high-risk group, respectively. (4) Conclusions: The majority of central pelvic recurrences in RT-naive EC women can be successfully salvaged with radiotherapy. However, survival in patients with high-risk disease remains poor and warrants a more individualized approach to optimize outcome