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IN THE NEWS
GENERAL SURGERY NEWS / AUGUST 2021
Colorectal Liver Metastases continued from page 1
missing live metastases, which are not visible on high-quality liver imaging and not detectable in the OR (Curr Colorectal Cancer Rep 2014;10:204-210). Dr. Aloia argued that disappearing liver metastases should absolutely be resected. “It is rare for patients who present with resectable liver metastases treated with a short course of neoadjuvant chemotherapy to develop a disappeared liver metastasis, and in the rare case that they do develop a disappeared liver metastasis, the tumors are rarely missing liver metastases but can typically be detected intraoperatively,” Dr. Aloia said. According to Dr. Aloia, disappearance on imaging rarely equates to a pathologic complete response (J Gastrointest Surg 2010;14[11]:1691-1700; Cancer 2010;116[6]:1502-1509). “We cannot rely on the imaging to tell us that a lesion that is about to disappear will become a nonrecurrent tumor,” he said. Dr. Aloia said at-risk lesions, most commonly encountered as small tumors in a multifocal patient, should have fiducial markers placed prior to preoperative systemic chemotherapy. Short-course preoperative systemic therapy should be halted as soon as a response is identified in a resectable patient (Lancet 2008;371[9617]:963-965). “If the intent is to treat with preoperative therapy limited to only two or three months, this strategy combined with judicious fiducial marker placement are both well used preventative measures to avoid the distress of missing metastases in the operating room,” he said. Dr. Aloia said becoming an expert in intraoperative ultrasound is important (J Am Coll Surg 2005;201[4]:517-528).
“Certainly in the setting of a previously treated patient, direct ultrasound examination with the probe on the liver may be our best imaging modality, and we need to maximize its ability to identify small and disappeared lesions to make sure that they do not reach the category of a missing lesion in the operating room,” he said. Dr. Aloia pointed out that surgeons have many surgical tools to choose from these days. For patients with bilobar colorectal liver metastases, surgical options now include anatomic hepatectomy, one-stage parenchymal sparing hepatectomy, traditional two-stage hepatectomy with or without portal vein embolization, associated liver partition and portal vein ligation for staged hepatectomy, local ablative techniques, and hepatic arterial infusion therapy (Surgery 2017;162[1]:12-17). “As we look at the spectrum of lesion status from progressing to all the way to missing lesions, it is really the responding and disappearing, but not disappeared or missing lesion, that has the best prognosis with surgery,” Dr. Aloia said. “Therefore, I would argue that the disappearing liver metastases is the ideal clinical situation that should be operated on.”
Observing Disappearing Liver Metastases Is a Good Option Dr. Leah Melstrom, a liver surgeon at City of Hope, offered a somewhat contrary opinion. “I am here to argue the point today that, indeed, resection of disappearing colorectal liver metastases is not a mandate. Not all disappearing colorectal liver metastases merit resection,” Dr. Melstrom
‘As we look at the spectrum of lesion status tus from progressing to all the way to missing lesions, ions, it is really the responding and disappearing, g, but not disappeared or missing lesion, that has the best prognosis with surgery. Therefore, I would argue that the disappearing liver metastases ases is the ideal clinical situation that should be operated on.’ —Thomas Aloia, MD said. “There is a reasonable chance that a disappearing lesion will not return, and I will argue that if it does return, there will remain treatment options. And lastly, and most importantly, if it does return, this small lesion will not likely dictate the survival of your patient.” Dr. Melstrom pointed out that isolated liver metastases can account for up to 25% of metastatic colorectal cancer presentation. “Since the early 2000s, the response rates have been upwards of 70% with FOLFOX [5-fluorouracil, leucovorin, oxaliplatin], FOLFIRI [irinotecan, 5-fluorouracil, leucovorin] and the biologics, which include bevacizumab, panitumumab [Vectibix, Amgen] and cetuximab [Erbitux, ImClone],” she said. “This improvement in systemic therapy has led to the phenomenon of disappearing liver colorectal metastases to occur in up to 5% to 25% of patients based on the series that you look at.” Dr. Melstrom said all can agree that resection of isolated colorectal liver metastases is associated with improved survival, and pathologically complete response to chemotherapy in these lesions is also associated with improved survival. However, disappearing colorectal liver metastases on cross-sectional imaging after
T Table 1. Sensitivity and Specificity at Diagnosis of Colorectal Liver Metastases C Sensitivity
Specificity
74%
93.9%
CT C
82.1%
73.5%
MRI M
93.1%
87.3%
PET/CT P
Source: J Magn Reson Imaging. 2018;47(5):1237-1250. S
chemotherapy does not routinely equate to a pathologic or clinical complete response (Dig Surg 2011;28[2]:114-120; Cancer 2010;116[6]:1502-1509; J Gastrointest Surg 2010;14[11]:1691-1700). In a systematic review of 15 studies involving 479 patients with disappearing colorectal liver metastases, the median age was 59 years, the median number of lesions per patient was one to 8.8, the median size of liver metastases prior to chemotherapy was 1.07 cm, and the median number of cycles of chemotherapy was approximately eight (Surg Oncol 2019;29:7-13). Factors found to be associated with disappearing colorectal liver metastases included lesions that were smaller than 2 cm, increased number of colorectal liver metastases (at least three), presentation of synchronous disease, history of oxaliplatin-based chemotherapy and increased number of treatment cycles. “Just as size and number of these lesions matters, the imaging modality also matters,” Dr. Melstrom said. There are limited data that fluorodeoxyglucose (FDG)-PET is more sensitive and more specific than a CT scan after neoadjuvant chemotherapy (Gastrointest Surg 2007;11[4]:472-478). FDGPET and CT sensitivity are lowered after neoadjuvant chemotherapy (Gastrointest Surg 2007;11[4]:472-478; Ann Surg Oncol 2009;16[5]:1247-1253). “Several factors contribute to this. Chemotherapy has the capability of inducing steatosis and steatohepatitis, and plus there is a decrease contrast differentiation between tumors and the background fatty liver,” she said. Dr. Melstrom said MRI is superior and may be able to compensate for these factors. “The data on MRI in this
Table 2. Imaging in Disappearing Colorectal Liver Metastases and Their Accuracy T Number of Patients
dCRLM With Complete Response CT
MRI
+IOUS
Median Follow-up (months)
Radiology. 2017;284(2):423-431
87
35%
78%
94%
12
J Surg Oncol. 2018;117(2):191-197
20
59%
85%
86%
27
HPB. 2018;20(8):708-714
59
51%
65%
92%
27
S Source: World J Surg Oncol. 2020;18(1):264. d dCRLM, disappearing colorectal liver metastases; IOUS, intraoperative ultrasound
