The management of colorectal cancer is a complex endeavor that requires treatment individualization founded on molecular characterization of the tumor, an in-depth understanding of the patient, and an appreciation of the interaction between the two. Patients are initially managed based on curability vs noncurability, and an accurate, dispassionate assessment of this fundamental differential is critical to providing optimal care. Failure to recognize a realistic opportunity for cure is unacceptable. That said, failure to recognize and/or failure to accept that a patient is not, in fact, realistically curable, can lead to use of inappropriate therapies and procedures that can have substantial and unnecessary toxicities and risks.
Resectability and Curability
For all practical purposes, the only patients with metastatic colorectal cancer who have a realistic potential for cure are those with a limited number of metastases in an appropriate location such that all disease can be resected. However, not all patients who can have all metastatic cancer surgically resected are realistically resectable for cure. The term “resectable” has thus become a source of confusion in recent years. In one context, it can mean that it is technically feasible to remove the cancer under discussion; that is, we can expect that an operation would remove all tissue containing macroscopic disease, with clear margins of resection, in a manner that would still be compatible with life. As such, a tumor that encases the celiac trunk would be unresectable, since its removal would require removal of a critical vascular structure. In contrast, a patient with two lung metastases, three liver metastases, two periportal lymph node metastases, and an ovarian metastasis would be, within this context of the word, technically resectable.
However, such a patient would not be realistically resectable for cure, and there lies the source of confusion. Historically, as the once-heretical concept of performing curative-intent surgery on patients with liver metastases of colorectal cancer was being established, the term “resectable” was used colloquially to mean “resectable with a realistic chance of cure.” Over time, the two meanings of “resectable” have become blurred. It is important to be clear in discussions, with each other and with our patients, which meaning is being assigned to the word “resectable” at the time of its use. Too often, the term “resectable” may mean different things to two individuals participating in the same conversation. Resection with realistic curative intent is part of standard practice; however, resection when the chance of actual cure is virtually nil has become increasingly common. Whether this is truly in our patients’ best interest or not is a matter of disagreement and debate among experts in the field. I believe that when we refer to a patient with metastatic cancer as being “resectable,” it should mean “resectable for cure.” If the risks and expense of resection are to be incurred in a setting in which cure (not some other soft-endpoint metric such as extended progression-free survival, but cure) is not a realistic goal, then both the doctors and the patient should have a clear understanding of this truth. It is noteworthy in this context that a published long-term experience from Memorial Sloan Kettering shows that patients with three or fewer liver metastases and no extrahepatic disease had reasonable cure rates; however, patients with greater numbers of hepatic lesions, while found to have an overall favorable long-term survival, had a virtually nonexistent cure rate, defined in terms of absence of cancer recurrence over the next 5 to 10 years.
When patients have disease that is liver-dominant with isolated lung metastasis, the potential for cure still exists[2-4]; however, when the cancer has spread to intra-abdominal or periportal lymph nodes, for all practical purposes, these patients are incurable and should not be considered candidates for curative-intent resection.
The concept of “conversion to resectability” has been largely misunderstood. Patients are potentially convertible from incurable to curable if only a small number of oligometastatic lesions in a single organ are in close proximity to a critical vascular structure such as a hepatic vein. In such patients, chemotherapy may decrease the size of the lesion and create a potential plane for resection. Patients with multiple sites of extrahepatic disease that appear to disappear on CT scans or go cold on a PET scan should not be regarded as having been converted to resectable status, as the chance of pathologic complete resection of all cancer is virtually nil.
For patients deemed potentially resectable for cure, a multidisciplinary management approach is required. Coordination between the liver surgeon, the colorectal surgeon, and the medical oncologist for determination of timing and sequencing of therapy is necessary to provide an optimal result.
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