RESUMEN
Background: According to international guidelines, standard treatment (ST) with curative intent in cervical cancer (CC) comprises radical hysterectomy and pelvic lymphadenectomy in early stages (International Federation of Gynecology and Obstetrics (FIGO) 2009 IB1, IIA1), adjuvant chemoradiation is recommended based on risk factors upon final pathology. Definitive chemoradiation is recommended in locally advanced stages (FIGO 2009 IB2, IIA2, IIB). Total mesometrial resection (TMMR) with therapeutic lymph node dissection (tLND) without adjuvant radiation has emerged as a promising treatment. Here we compare oncologic outcome by TMMR + tLND or ST. Methods: In this observational cohort study, women treated according to international guidelines were identified in the population-based registries from Sweden and women treated with TMMR were identified in the Leipzig Mesometrial Resection (MMR) Study Database (DRKS 0001517) 2011-2020. Relevant clinical and tumour related variables were extracted. Recurrence-free survival (RFS) and overall survival (OS) by ST or TMMR was analysed with log-rank test, cumulative incidence function and proportional hazard regression yielding hazard ratios (HR) with 95% confidence intervals (CI), adjusted for relevant confounders. Findings: Between 2011 and 2020, 1007 women were included in the final analysis. 733 women were treated according to ST and 274 with TMMR. RFS at five years was 77.9% (95% CI 74.3-81.1) and 82.6% (95% CI 77.2-86.9) for the ST and TMMR cohorts respectively (p = 0.053). In early-stage CC, RFS was higher after TMMR as compared to ST, 91.2% vs 81.8% (p = 0.002). In the adjusted analysis, TMMR was associated with a lower hazard of recurrence (HR 0.39; 95% CI 0.22-0.69) and death (HR 0.42; 95% CI 0.21-0.86) compared to ST. The absolute difference in risk of recurrence at 5 years was 9.4% (95% CI 3.2-15.7) in favor of TMMR. In locally advanced CC, no significant differences in RFS or OS was observed. Interpretation: Compared to ST, TMMR without radiation therapy was associated with superior oncologic outcomes in women with early-stage cervical cancer whereas no difference was observed in locally advanced disease. Our findings together with previous evidence suggest that TMMR may be considered the primary option for both early-stage and locally advanced cervical cancer confined to the Müllerian compartment. Funding: This study was supported by grants from Centre for Clinical Research Sörmland (Sweden) and Region Stockholm (Sweden).
RESUMEN
Importance: The risks and benefits of thromboprophylaxis therapy after cancer surgery are debated. Studies that determine thrombosis risk after cancer surgery with high accuracy are needed. Objectives: To evaluate 1-year risk of venous thromboembolic events after major cancer surgery and how these events vary over time. Design, Setting, and Participants: This register-based retrospective observational matched cohort study included data on the full population of Sweden between 1998 and 2016. All patients who underwent major surgery for cancer of the bladder, breast, colon or rectum, gynecologic organs, kidney and upper urothelial tract, lung, prostate, or gastroesophageal tract were matched in a 1:10 ratio with cancer-free members of the general population on year of birth, sex, and county of residence. Data were analyzed from February 13 to December 5, 2023. Exposure: Major surgery for cancer. Main Outcomes and Measures: The main outcome was incidence of venous thromboembolic events within 1 year after the surgery. Crude absolute risks and risk differences of events within 1 year and adjusted time-dependent cause-specific hazard ratios (HRs) of postdischarge events were calculated. Results: A total of 432â¯218 patients with cancer (median age, 67 years [IQR, 58-75 years]; 68.7% women) and 4â¯009â¯343 cancer-free comparators (median age, 66 years [IQR, 57-74 years]; 69.3% women) were included in the study. The crude 1-year cumulative risk of pulmonary embolism was higher among the cancer surgery population for all cancers, with the following absolute risk differences: for bladder cancer, 2.69 percentage points (95% CI, 2.33-3.05 percentage points); for breast cancer, 0.59 percentage points (95% CI 0.55-0.63 percentage points); for colorectal cancer, 1.57 percentage points (95% CI, 1.50-1.65 percentage points); for gynecologic organ cancer, 1.32 percentage points (95% CI, 1.22-1.41 percentage points); for kidney and upper urinary tract cancer, 1.38 percentage points (95% CI, 1.21-1.55 percentage points); for lung cancer, 2.61 percentage points (95% CI, 2.34-2.89 percentage points); for gastroesophageal cancer, 2.13 percentage points (95% CI, 1.89-2.38 percentage points); and for prostate cancer, 0.57 percentage points (95% CI, 0.49-0.66 percentage points). The cause-specific HR of pulmonary embolism comparing patients who underwent cancer surgery with matched comparators peaked just after discharge and generally plateaued 60 to 90 days later. At 30 days after surgery, the HR was 10 to 30 times higher than in the comparison cohort for all cancers except breast cancer (colorectal cancer: HR, 9.18 [95% CI, 8.03-10.50]; lung cancer: HR, 25.66 [95% CI, 17.41-37.84]; breast cancer: HR, 5.18 [95% CI, 4.45-6.05]). The hazards subsided but never reached the level of the comparison cohort except for prostate cancer. Similar results were observed for deep vein thrombosis. Conclusions and Relevance: This cohort study found an increased rate of venous thromboembolism associated with cancer surgery. The risk persisted for about 2 to 4 months postoperatively but varied between cancer types. The increased rate is likely explained by the underlying cancer disease and adjuvant treatments. The results highlight the need for individualized venous thromboembolism risk evaluation and prophylaxis regimens for patients undergoing different surgery for different cancers.