Surgical therapy of (locally) advanced adenocarcinoma in the upper rectum - first results of the multicenter GAST-05 phase IIb study
English
The prospective, randomized, multicenter GAST-05 phase-IIb study (ISRCTN 35198481), funded by the German research Foundation, was designed to clarify whether partial mesorectal excision (PME, with a distal cancer-free safety margin of 5 cm) is sufficient compared to total mesorectal excision (TME) for patients with adenocarcinomas (cUICC stages ≥ II) in the upper rectum (> 12 cm from anal verge). The surgical results in participants of one GAST-05 study site were assessed, taking various clinicopathological parameters into account. Surgery was performed in 98 (median age: 69 years) patients (f: 33,7%, m: 66,3%), randomized to PME (experimental) vs. TME (control). Based on standardized staging procedures, surgery was evaluated in terms of feasibility, peri-/postsurgical assessment of specimen’s quality (according to MERCURY criteria), and of acute as well as late adverse events (AE) using the Dindo- classification and NCI-CTCAE-criteria (vs 3.0). Diverse clinico-pathological parameters (e.g. safety margins, circumferential resection margin (CRM), conversion rate between TME and PME, technique of anastomosis) were included in recurrence-free (RFS) and overall (OS) survival analyses using the logrank test, Kaplan-Meier estimator, and multivariable Cox proportional hazard regression models to test interaction effects between selected predictors. Postsurgical assessment of the specimen revealed UICC stages I to IV in 14.2%, 42.9%, 37.8% and 5.1%, respectively. PME (55.1%) and TME (44.9%) were performed with good, moderate, or poor quality in 84.7%, 14.3% and 1%, respectively. The preferred procedure was open (96,9 %) surgery (laparoscopic in 3,1%) and a protective ileostomy was carried out in 11.1 % (PME) and 79.6 % (TME). After PME, the quality of surgery (p = 0,08) and distal safety margins (p < 0,01) showed impact on the RFS. Within 6 months after surgery most common acute complications (all grades) resulted in abdominal wound healing disorders (WHD) and anastomotic leaks in 16.3% and 10.2%, respectively. The occurrence of fistulas, and urinary disturbances with 6.8% (p = 0.08) and 11.4% (p = 0.24) was more frequent after TME. Anastomotic leaks (AL) and wound healing disorders (WHD) had no significant impact on OS (p = 0.308; HR: 1.5; 95%-CI: 0.70 - 3.10). Late disorders (> 6 months after surgery) with CTCAE-grades > 2 were significantly higher after TME (36.4%) vs. PME (9.3%). The most frequent disorders (grade > 2) after TME were diarrhea, fecal incontinence and erectile dysfunction in 18.2%, 4.6% and 6.8% vs. only diarrhea in 9.3% after PME, respectively. Restrictive mean of RFS for stage II patients (108.9 months) was significantly better than for stage III (78.7 months; p<0.001). Tumor infiltration depth (< 5 vs. ≥ 5 mm; p < 0.031) and age (p < 0.005) had impact on RFS (univariable models). The recurrence rate was 25.6% after TME and 20.4% after PME, respectively, and no isolated local relapse has been observed. TME vs. PME in the upper third of the rectum has no influence on the occurrence of local and distant metastases, nor on the OS. PME should be used as a standard procedure for carcinomas in the upper third of the rectum (UICC grade 2/3) because it is associated with fewer acute complications and, above all, less severe late complications than after TME. Optimum surgical quality and compliance with the distal safety distance of 5 cm are crucial.
Keywords: cancer of the upper rectum; surgical results upper rectal cancer
Schlagwörter: Karzinome des oberen Rektums; chirurgische Ergebnisse des oberen Rektumkarzinoms
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http://dx.doi.org/10.53846/goediss-10021
