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 Colorectal carcinoma is the commonest cancer in Singapore.¹ Although long-term survival results are possible after treatment of the primary cancer, up to 80% of patients will develop metastases in their lifetime, usually in the liver, lung, bones or brain. Patients with stage IV cancers used to be considered "terminal" cases with median survival of only 4.5 months.² Recent advances in understanding of tumour biology and treatment strategies have resulted in significant improvements in outlook for metastatic colorectal cancer, affording hope in an otherwise dismal situation.
Isolated liver metastases
The liver forms the first pass organ for portal venous drainage from the colon. As such, it is the most frequently involved organ in metastases from colorectal cancers.³ Being the first pass organ also means that, not infrequently (up to 50-60%), the liver is the only site of metastases.4 This presents a unique opportunity for disease control in an otherwise metastatic situation.
Surgery is currently the only recognised treatment modality that offers reasonable "cure" in the setting of liver metastases, with survival rates of 25-45% at 5 years, and 22-26% at 10 years with operative mortality in established hepatobiliary (HPB) units of less than 5%.5,6,7,8 In contrast, chemotherapy at best prolongs median survival to 12 months using conventional agents9, and up to 18 months with newer agents like oxaliplatin.10,11 Long-term survival results with targeted therapy are currently unavailable.
Unfortunately, only 10-20% of patients are able to undergo surgery.12 The remaining are unsuitable because of (1) extrahepatic disease, (2) extensive metastases, (3) inability to obtain a resection margin, (4) insufficient residual liver reserve, and (5) overall poor condition. In these patients, treatment options include palliative chemotherapy, radiofrequency ablation (RFA), cryotherapy, or Yt90 microspheres.
The situation is obviously dismal.
Since surgery offers the only reasonable chance of cure, many centers have explored ways to increase operability. Liver resection for metastatic colorectal cancer to the liver was first described in 1943 and from then till the late 1970s, only solitary liver metastases were deemed resectable. With improvements in techniques, better post-operative care and significant reductions in mortality and morbidity, the possibilities for resection have expanded. In the 1980s and 1990s, up to 3 tumours with the largest not exceeding 3cm in size were considered operable. Today, the ability to achieve an "R0" resection (i.e. no gross residual tumour with clear margins all around the resected lesion), while retaining sufficient liver reserve, remains the most important criteria in patient selection, irrespective of size and number of tumours.
Newer concepts have been developed in the last decade to further increase the operability rate include the role of neoadjuvant chemotherapy in down-staging disease and converting inoperable disease to resectable liver metastases.13,14 The overall 5-year survival in this group was not too dissimilar to the results in initially-resectable patients.15,16 Techniques like metastasectomy to conserve residual parenchyma, staged resections to allow liver regeneration, combined techniques with RFA/cryosurgery for multiple lesions have been variously explored and do offer some degree of optimism.
Isolated lung metastases
Involvement to the lung has traditionally been viewed pessimistically because of the escape beyond the first "filter"(liver), to the second "filter"(lung). With the encouraging results seen with liver resections, surgery for isolated lung metastases have also been attempted both by conventional and thoracoscopic methods (VATS), and it is now common to see 5-year survival rates of up to 60% with such resections.17,18
Combined liver and lung metastases
In situations where patients have both liver and lung metastases, combined resections are currently advocated provided it is possible to achieve an "R0" operation of total gross disease clearance. The lung resection is commonly 6 weeks after the liver resection and the results of such combined resections have been favourable provided both procedures are done by experienced surgeons in high-volume dedicated centers off ering surgical oncology, HPB and thoracic surgery services.
Liver and concomitant intra-abdominal lymph node metastases
Nodal disease in the drainage of the original colonic tumour probably represents loco-regional recurrence and is best resected at the same sitting as the liver resection. Para-aortic and/or paracaval nodes probably represent lymphatic metastases beyond and the place of resection is not so evident. Recent reports from high-volume cancer centers report fairly good outcomes with surgery in selected cases, provided gross disease clearance is possible, and this can be extended also to other forms of extrahepatic disease.19
Conclusion
Although the majority of early-stage colorectal cancer patients have good long-term outcomes after surgery and adjuvant therapy, a significant number do recur, relapse or metastasise. When the metastases are confi ned to the liver and/or lung, only surgery offers long-term survival and this method of therapy should be advocated aggressively. Newer concepts of neoadjuvant chemotherapy, staged resections, combined procedures and simultaneous extrahepatic resections increase the hope off ered to an otherwise dismal situation. It is important therefore that all metastatic colorectal cancer patients be properly evaluated in a specialised unit for a potential curative resection. Only then will there be new hope for life. |
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References
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