Claus Høgdall

Vaginal and pelvic recurrences and salvage treatments in a cohort of Danish endometrial cancer patients not given adjuvant radiotherapy

In Denmark, adjuvant radiotherapy has gradually been omitted after surgery in endometrial cancer. This study analyses the impact of this strategy on patterns of recurrence and outcome after salvage radiotherapy. Moreover, the potential effect of adjuvant radiotherapy is estimated in the non-low-risk cohort. The cohort included 3723 consecutive Danish patients with endometrial cancer who had radical surgery without adjuvant treatment (2005-2012). The patients were divided into low-risk (stage 1A, endometrioid, grades 1, 2 and no lymph-vascular space invasion) and non-low-risk. Crude/actuarial recurrence rates evaluated the number of patients who might have benefited from additional adjuvant radiotherapy. Within 9 years' observation time using crude recurrence rates, 13.4% recurred.The rate of isolated vaginal recurrences was 2.9% in low-risk compared with 6.7% in non-low-risk patients. Isolated pelvic recurrences were 0.8% in low-risk compared with 2.1% in non-low-risk patients. In all, 15.8% of non-low-risk patients died from endometrial cancer, mainly due to primary or secondary non-local recurrences (a later non-local recurrence after a primary isolated local recurrence). Only 0.6% and 1.1% of all non-low-risk patients died from an isolated vaginal or pelvic recurrence, respectively. In all, 86% of all patients with an isolated vaginal recurrence were treated with curative intent. Of these, 72% were given radiotherapy with a local control rate of 91% (crude rate). However, even though only 5.8% died of an unsuccessfully treated isolated vaginal recurrence after curative intended radiotherapy, 23.1% died from a secondary non-local recurrence, while 22.3% died from other causes. The Danish strategy of omitting adjuvant radiotherapy is safe. Adjuvant external beam radiotherapy may have prevented isolated local recurrences in 8.7% of the Danish non-low-risk patients, but a majority of these patients were salvaged by curative radiotherapy with 91% and 70% crude local control rates for isolated vaginal and isolated pelvic recurrences, respectively.

Survival and recurrence in stage II endometrial cancers in relation to uterine risk stratification after introduction of lymph node resection and omission of postoperative radiotherapy: a Danish Gynecological Cancer Group Study

To evaluate survival and recurrence in stage II endometrial cancer in relation to uterine risk stratification. Outcome for stage II was compared before and after the introduction of lymph node (LN) resection and omission of all postoperative radiotherapy. The cohort consisted of 4,380 endometrial carcinoma patients radically operated (no visual tumor, all distant metastasis removed) (2005-2012) including 461 stage II. Adjusted Cox regression was used to compare survival and actuarial recurrence rates. Uterine risk factors (low-, intermediate-, and high-) were the strongest predictors of survival and recurrence in stage II. Stage II low-risk having a prognosis comparable to low-risk stage I (grade 1-2, <50% myometrial invasion), whereas cervical invasion significantly increased the risk of recurrence and decreased cancer-specific survival in intermediate- and high-risk compared to the corresponding stage I risk groups. In 355 cases of 708 with cervical stromal invasion, LN-resection showed 27.9% with LN metastasis and upstaged 18.1% from stage II to IIIC resulting in longer survival and lower recurrence in LN-resected compared to non-LN resected stage II. Radical as compared to simple hysterectomy did not alter survival. Treatment with external beam radiotherapy decreased local recurrence without affecting survival. Uterine risk groups are the strongest predictors for survival and recurrence in stage II patients and should be considered when advising adjuvant therapy. LN-resected stage II had increased survival and decreased recurrence. Omitting radiotherapy increase vaginal recurrence without affecting survival.

Oncological outcomes after vaginal and robotic-assisted radical trachelectomy in patients with cervical cancer - A single-center prospective cohort study

The aims of this study are to evaluate the oncological outcomes of robotic-assisted radical trachelectomy (RART) compared with radical vaginal trachelectomy (RVT) for localized early-stage cervical cancer in a national cohort. RVT was introduced in 2003 in Denmark and nationally centralized to Copenhagen Univeristy Hospital. In 2014 the procedure advanced to a robotic-assisted approach. Perioperative and oncological data has been prospectively reported to the Danish Gynecological Cancer Database (DGCD) which is continuously developed and updated. All patients undergoing radical trachelectomy were included in this prospective cohort study. Data was extracted from DGCD and manually validated through electronic medical journals and The Danish Pathology Registry. A total of 206 patients underwent radical trachelectomy, with 78 patients undergoing RART and 128 patients undergoing RVT. No significant differences were observed in the microscopic free margins of the trachelectomy specimens. A total of seven (5.5%) patients undergoing RVT and two (2.6%) patients undergoing RART had recurrences (p = 0.403). No significant differences in recurrence-free survival were found between the groups, both in the unadjusted (HR 0.51 (0.11-2.47)) and adjusted analyses (HR 0.80 (0.16-3.96)). In this large single-center cohort, oncological safety of RART is equal to RVT for patients with localized cervical cancer and a fertility desire.

Risk factors for early death among ovarian cancer patients: a nationwide cohort study

To characterize ovarian cancer patients who die within 6 months of diagnosis and to identify prognostic factors for these early deaths. A nationwide cohort study covering ovarian cancer in Denmark in 2005-2016. Tumor and patient characteristics including comorbidity and socioeconomic factors were obtained from the comprehensive Danish national registers. A total of 5,570 patients were included in the study. Three months after ovarian cancer diagnosis 456 (8.2%) had died and 664 (11.9%) died within 6 months of diagnosis. Adjusted for age and comorbidity, patients who died early were admitted to hospital significantly more often in a 6-month period before the diagnosis (odds ratio [OR]=1.61 [1.29-2.00], and OR=1.47 [1.21-1.78]), for patients who died within 3 and 6 months respectively). Low educational level (OR=2.11), low income (OR=2.50) and singlehood (OR=1.90) were factors significantly associated with higher risk of early death. The discriminative ability of risk factors in identifying early death was assessed by cross-validated area under the receiver operating characteristic curve (AUC). The AUC was found to be 0.91 (0.88-0.93) and 0.90 (0.87-0.92) for death within 3 and 6 months, respectively. Despite several admissions to hospital, the ovarian cancer diagnosis is delayed for a subgroup of patients, who end up dying early, probably due to physical deterioration in the ineffective waiting time. Up to 90% of high-risk patients might be identified significantly earlier to improve the prognosis. The admittance of the patients having risk symptoms should include fast track investigation for ovarian cancer.