Early distant relapse after optimal local control in locally advanced rectal cancer
© Gallego-Plazas et al; licensee BioMed Central Ltd. 2008
Received: 08 January 2008
Accepted: 14 July 2008
Published: 14 July 2008
We present a case of locally advanced rectal cancer with initial optimal local control after neoadjuvant concurrent chemoradiotherapy followed by surgery; early liver recurrence then occurred and was treated again with curative intent with neoadjuvant combination chemotherapy followed by liver surgery. We reflect on this difficult problem and discuss relevant topics to this case report.
A male of 56 years of age with clinical history of hyperuricemia and gout was hospitalised because of rectal bleeding. His symptoms had started two months prior, and he had been diagnosed with haemorrhoids.
Five weeks after surgery the patient was again referred to Clinical Oncology, were, once we had confirmed the absence of disease by blood analysis and imaging, adjuvant treatment was planned. Adjuvant fluorouracil-based chemotherapy was then administered in order to complete a total of six months neoadjuvant and adjuvant treatment [3, 4]. Thoracic-abdominal-pelvic CT performed shortly after completing adjuvant chemotherapy, and this showed only surgical changes; colonoscopy through the end colostomy was normal, and blood analysis, including CEA and CA 19.9 levels, were also normal. The patient entered into our three-monthly periodic follow-up program .
Concurrent preoperative chemoradiotherapy has proven superior to other treatment strategies against locally advanced rectal cancer. Neoadjuvant combined treatment reduces local relapse compared to adjuvant combined treatment  and exclusive preoperative radiotherapy [9, 10]. Nevertheless, this benefit not always means an increase in terms of overall survival. Inadequate doses of chemotherapy, with radiosensitizer but without systemic effect, and sub-optimal chemotherapy strategies may both well explain this paradox. The clinical case previously commented is an example of what may occur in early stage rectal cancer patients. Far from presenting local relapse, distant metastases may occur, and is being seen with increasing frequency.
By combined neoadjuvant chemoradiotherapy, followed by surgery including total mesorectal excision, it is clear that very good local control of rectal cancer can be achieved, with five-year local relapse rates of 6–8% [8–10]. This very good local control rate may be optimized when effectiveness of neoadjuvant treatment is demonstrated after surgery of regressive disease, and adjuvant chemotherapy with a similar regimen to that previously used in the neoadjuvant setting is completed . The challenge on the horizon is then to reduce distant relapse, in order to prolong overall survival. The best way to accomplish this goal might be to divide preoperative treatment into two steps: neoadjuvant combined chemotherapy followed by neoadjuvant concurrent chemoradiotherapy. First step would include only combined chemotherapy, so that optimal doses and regimens with demonstrated systemic effect could be safely administered, within an attempt to control micrometastatic systemic disease. In a second stage treatment would focus on local control by concurrent administration of radiotherapy and chemotherapy, this time using adjusted doses in order to achieve synergistic effect avoiding excessive toxicity. This approach has already been partially succesfully tested in phase II clinical trials , and is yet to be confirmed in on course phase III clinical trials.
Fortunately, continuous investigation-based advances have made potentially curative treatment strategies available to patients, as the one here reported, even in the case of distant relapse, and when no evidence of extrahepatic disease is found . Combination chemotherapy with fluroropyrimidines (fluorouracil or capecitabine), oxaliplatin, or irinotecan, and-more recently-bevacizumab or cetuximab, has improved response rates, progression-free survival and, in three trials, overall survival [12–15]. Combinations of three of these drugs have achieved best response rates so far in metastatic colorectal cancer, and so should be advised in the neoadjuvant setting of potentially resectable liver only metastatic disease [12–15]. Recent results favour, in case of resectable or potentially resectable liver only metastatic disease, combination systemic perioperative treatment in order to achieve best overall survival [7, 16, 17]. Eventhough complete clinical response to neoadjuvant chemotherapy may be achieved, resection of metastatic sites, when possible, is mandatory .
In conclusion, although recent improvements in treatment of advanced colorectal cancer make it possible to offer certain subsets of patients potential healing even in case of relapse after early disease, future treatment strategies in locally advanced rectal cancer need to focus not only in achieving optimal local control but in avoiding distant failure.
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