When It Comes to the Efficacy of Metastasectomy, Biology Is King

“Biology is King; selection of cases is Queen, and the technical details of surgical procedures are princes and princesses of the realm who frequently try to overthrow the powerful forces of the King and Queen, usually to no long-term avail, although with some temporary apparent victories.”

This insight, shared by Blake Cady, MD, is certainly as true today as when first proclaimed over a decade and a half ago.[1] The statement applies as much to metastasectomy as it does to management of primary tumors. Colorectal liver metastasis is perhaps the best studied scenario of metastasectomy for oligometastatic solid tumor. Over 3 decades of experience with resection of liver metastases has taught us that 20% to 50% of patients who undergo liver resection will be alive 5 years later (see the article by Dr. Weiser and colleagues on page 1074 of this issue). The most important predictors of long-term survival following resection of colorectal liver metastases are the number of metastases, involvement of lymph nodes by the primary tumor, maximum size of metastases, preoperative CEA level, and extrahepatic spread.[2] Conspicuous in their absence from this important list of prognosticators is any reference to controllable technical factors like resection margin or even the use or lack of use of systemic chemotherapy before or after metastasectomy.[3] In fact, the prognosis following metastasectomy has changed little from what is was almost 2 decades ago, when chemotherapy was rarely used before or after resection of metastases.[4] Despite significant advances in systemic therapy for colon cancer, patient selection remains the best way to achieve long-term survival following metastasectomy for colorectal liver metastases.

Favorable biology is of paramount importance to the excellent outcome enjoyed by many in the highly selected, good prognostic groups. While metastasectomy for oligometastatic colorectal liver metastases can be justified on the basis of these excellent outcomes, the same cannot be said of oligometastatic pancreatic cancer liver metastases.[5,6] Even the most highly selected patients with oligometastatic pancreatic cancer have a dismal prognosis following metastasectomy. In contrast, metastasectomy for neuroendocrine liver metastases, another disease with relatively poor chemosensitivity, results in excellent long-term survival.[7]The only good explanation for these different outcomes is the biology of disease. The data suggest that it has little to do with colorectal cancer chemosensitivity and the relative insensitivity of ductal pancreatic cancer.

Pulmonary metastectomy for highly selected patients with isolated, resectable colorectal lung metastases, has a favorable prognosis, with over 29% to 68% of patients living 5 years.[8] Pulmonary metastasectomy for renal cell carcinoma can also yield long-term survival in 30% to 50% of patients.[9]. Patient selection is of paramount importance, as the outcome is poor unless the disease-free interval between the diagnosis of the primary tumor and the development of metastases is long and the disease is limited and encompassable. There have been similar findings with pulmonary metastasectomy for soft-tissue sarcoma and melanoma. Testicular cancer and osteosarcoma patients can also benefit from pulmonary metastasectomy.[9] However, systemic chemotherapy seems to play a major role in improving the outcomes of these patients. This is the exception that proves the rule; it’s biology and selection all the way!

References:

1. Cady B. Basic principles in surgical oncology. Arch Surg. 1997;132:338-46.

2. Spelt L, Andersson B, Nilsson J, Andersson R. Prognostic models for outcome following liver resection for colorectal cancer metastases: a systematic review. Eur J Surg Oncol. 2012;38:16-24.

3. Mitry E, Fields AL, Bleiberg H, et al. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008;26:4906-11.

4. Fong Y, Cohen AM, Fortner JG, et al. Liver resection for colorectal metastases. J Clin Oncol. 1997;15:938-46.

5. McKenzie S, Mailey B, Artinyan A, et al. The incidence and outcomes of pancreatectomy in patients with metastatic pancreatic adenocarcinoma. JOP. 2010;11:341-7.

6. Gleisner AL, Assumpcao L, Cameron JL, et al. Is resection of periampullary or pancreatic adenocarcinoma with synchronous hepatic metastasis justified? Cancer. 2007;110:2484-92.

7. Reddy SK, Clary BM. Neuroendocrine liver metastases. Surg Clin North Am. 2010;90:853-61.

8. Gonzalez M, Poncet A, Combescure C, et al. Risk factors for survival after lung metastasectomy in colorectal cancer patients: a systematic review and meta-analysis. Ann Surg Oncol. 2013;20:572-9.

9. Hornbech K, Ravn J, Steinbruchel DA. Current status of pulmonary metastasectomy. Eur J Cardiothorac Surg. 2011;39:955-62.