br The OS rate after the first
The OS rate after the first metastasectomy for the first recurrence was defined as the interval from the date of the first metastasectomy to any-cause mortality or the date of the last follow-up (Fig. 1). The recurrence-free survival (RFS) after the surgical resection for the initial recurrence (RFS1) was defined as the interval from the date of the first metastasectomy to the recurrence from colorectal cancer or all-cause mortality, whichever occurred first. The RFS after the first (RFS2) and second (RFS3) repeated resections was defined as the time from the date of the first and second repeat surgeries, respec-tively. The primary endpoints for this JNJ-42153605 study were survival and clinical recurrence.
This study protocol was approved by the institutional review board of the Asan Medical Center (registration no:
Please cite this article as: Yang KM et al., Benefits of repeated resections for liver and lung metastases from colorectal cancer, Asian Journal of Surgery, https://doi.org/10.1016/j.asjsur.2019.03.002
Repeat metastasectomy from colorectal cancer 3
Table 1 Demographic and clinical characteristics of thepatients undergoing 1st metastasectomy.
Primary tumor characteristics
Location of the primary tumor
Type of metastasis
XELOX, capecitabine-oxaliplatin; FOLFOX, folinic acid-
efluorouracileoxaliplatin; FOLFIRI, folinic
2.2. Statistical analysis
Survival curves were generated using the KaplaneMeier method, and the differences between curves were evalu-ated using the log-rank test. With regard to comparison of the RFS, patients who underwent first, second, and third metastasectomy were considered as the independent groups eligible for the analysis. Multivariate analyses for survival included the variables that showed statistical sig-nificance in the log-rank test and were performed using the Cox proportional hazards model, with a 95% confidence interval (CI), to assess the risk factors associated with overall survival. Statistical significance was defined as p < 0.05, and all analyses were performed using the SPSS software version 21 (IBM Corp., Armonk, NY).
Of the 248 patients who underwent a first metastasectomy for hepatic and/or pulmonary metastases, 54% developed a second recurrence. Of these patients, 52 underwent a second metastasectomy, and 52% of these patients devel-oped a third recurrence. Of these 27 patients, 14 under-went a third metastasectomy, 71% of whom developed a fourth recurrence (Fig. 1). The initial sites of recurrence after surgery were the liver group (n Z 115), lung group (n Z 117), and liver/lung group (n Z 16). Among the 133 patients who had recurrence after the first meta-stasectomy, 81 patients underwent nonsurgical treatment. Among them, 6 patients had bone or brain metastasis, 37 (46%) patients had multiple site metastasis or peritoneal seeding, 23 patients had lung metastasis, 13 patients had liver metastasis, and 2 patients had local recurrence. Among the 23 patients with pulmonary metastasis, 11 pa-tients had multiple recurrences in both lobes, 8 patients underwent radiation therapy, and 4 patients refused further treatment. Among the 13 patients with hepatic recurrence, 7 patients had multiple recurrences in both lobes, 4 patients underwent radiation therapy, and 2 pa-tients refused further treatment. Two patients who had local recurrence refused pelvic exenteration.
The profile of the patients who were included in this study is shown in Table 2. Fifty-two and 14 patients un-derwent a second metastasectomy for a second recurrence and a third metastasectomy for a third recurrence, respectively. The most common repeated resection site was the lung, where the majority of tumors that underwent repeated resections were isolated single lesions. The most common type of metastasectomy was a wedge resection for lung metastasis and a partial hepatectomy for liver metastasis. Postoperative complications were classified according to the Clavien-Dindo Classification system. Se-vere complications occurred in one out of 52 patients after the second metastasectomy and in one out of 14 patients after the third metastasectomy. There were no life-threatening complications or death from any repeat sur-gery. Overall recurrence rates were 51% and 77% in the first and third metastasectomy groups, respectively.
3.1. Overall survival (OS) rate after first metastasectomy
Relapse occurred in 133 patients after the first meta-stasectomy, and a second metastasectomy was performed in 52 patients. The results were classified according to the following subgroups: 5-year and 10-year OS rates in the second metastasectomy group (n Z 52) were 82% and 39%, and that of the subgroup with nonsurgical treatment on second recurrence were 36% and 23% (Fig. 2A, p < 0.001), respectively. The sequential outcomes of the patients are