Leucovorin

TO THE EDITOR: I read with interest the article "Care of Cancer Survivors" (1) in the February 15, 2005, issue of American Family Physician. I was surprised to see such a firm recommendation for aggressive follow-up of fully resected colon cancer with inaccurately documented references. The authors recommend carcinoembryonic antigen monitoring every three months for the first two years following treatment, and then every six months for the next three years; this is controversial and not a fully endorsed recommendation. According to my investigation, the National Comprehensive Cancer Network is the only medical group recommending routine carcinoembryonic antigen monitoring testing, and no major medical organization recommends routine computed tomography (CT) scanning as listed in the article. (1) Also, the references listed in the article (1) far from fully endorse routine aggressive follow-up with carcinoembryonic antigen monitoring testing and/or CT scanning.

The latest Cochrane article I could find is not from 2004, as noted in the article, (1) but was last updated in 2002 (2) and in no way firmly recommends aggressive follow-up. In its summary recommendations, it states: "Because of the wide variation in the follow-up programmes used in the included studies, it is not possible to infer from the data the best combination and frequency of clinic (or family practice) visits, blood tests, endoscopic procedures and radiological investigations to maximi[z]e the outcomes for these patients. Nor is it possible to estimate the potential harms or costs of intensifying follow-up for these patients." (2)

The other reference (3) listed by the authors does not recommend aggressive follow-up with carcinoembryonic antigen monitoring and CT scanning either but discusses the limitations of present evidence in decision making.

A 2004 review article (4) discusses the controversy around aggressive follow-up and compares the recommendations of individual organizations.

The primary listed reference from Cochrane presents a more balanced overall recommendation: "the results of this review support the general principle of clinical follow-up for patients with CRC [colorectal cancer] after curative treatment. the exact details of the optimal follow-up regimen still need clarification." (2)

PHIL LAWSON, M.D.

Ammonoosuc Community Health

25 Mt. Eustis Rd. Littleton, NH

03561

REFERENCES

(1.) Sunga AY, Oeffinger KC, Hudson MM, Mahoney MC. Care of cancer survivors. Am Fam Physician 2005; 71:699-706.

(2.) Jeffery GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev 2002;(1):CD002200.

(3.) Renehan AG, Egger M, Saunders MP, Impact on survival of intense follow up after curative resection for colorectal cancer: systematic review and meta-analysis of randomized trial. BMJ 2002;324:813.

(4.) Pfister DG, Benson AB III, Somerfield MR. Clinical practice. Surveillance strategies after curative treatment of colorectal cancer. N Engl J Med 2004;350:2375-82.

IN REPLY: We would like to thank Dr. Lawson for his remarks. Several of his comments are already addressed in our review. (1) Specifically, with regard to surveillance following treatment for colorectal cancer, we stated "it is not possible to infer an optimal combination of tests or frequency of clinical follow-up for intensive colorectal cancer surveillance." (1)

We have cited general recommendations for follow-up of patients with colorectal cancer endorsed by the National Comprehensive Cancer Network (NCCN). The NCCN guidelines (2) are in line with recommendations by the American Society of Clinical oncology (ASCO) and the American Society of Colon and rectal Surgeons (ASCRS). NCCN and ASCO recommend carcinoembryonic antigen (CEA) testing every three months for at least two years (ASCO recommends testing for at least two years; NCCN for two years, then every six months for three more years), whereas ASCRS recommends monitoring CEA levels a minimum of three times per year during the first two years of follow-up. A recent pooled analysis (3) from 17 adjuvant randomized trials showed that more than 25 percent of recurrences occur beyond three years following surgery. Thus, we feel that a five-year follow-up, as recommended by NCCN, is favored.

Computed tomography (CT) remains a controversial modality of colorectal cancer surveillance and is not recommended routinely by any organization at this point. However, recent studies (4,5) suggest that early asymptomatic recurrences can be detected by CT in the absence of CEA elevations. A significant number of these recurrences are amenable for curative resection, leading to an improved survival in comparison with unresectable patients. (4,5) At this time, CT cannot be recommended routinely as a surveillance modality for colorectal cancer. CT scans should be obtained in the work-up of symptomatic patients or in the presence of elevated CEA and can be considered in patients at high risk of recurrence, such as those with stage III disease.

The importance of rigorous surveillance in colorectal cancer is based on the prospect of salvage surgery at the time of recurrence. resection of isolated recurrences can lead to a five-year survival of about 30 percent, (5) whereas five-year survivorship following chemotherapy in patients with unresectable recurrent disease is well below 10 percent. The ability to achieve a successful curative resection is highly compromised in the setting of symptomatic detection. This is supported by a study (4) of 154 relapses seen in a randomized phase III study of adjuvant fluorouracil/leucovorin in patients with stage II and III disease. At the time of publication of this study, none of the patients with resected symptomatic recurrences were alive at five years, whereas 18.6 and 25.9 percent of those with resected CEA recurrences and resected CT recurrences, respectively, remained alive. whether the implementation of an intensive surveillance schedule that includes frequent CT scans is affordable to society is yet to be determined and should be the subject of future cost-effectiveness analysis studies.

Finally, the publication year listed for the Cochrane review6 reference in the article was inadvertently changed; the correct publication year for this work is 2002.

ANNETTE SUNGA, M.D., M.P.H.

MARTIN MAHONEY, M.D., PH.D.

Roswell Park Cancer

Institute Elm and Carlton

Streets Buffalo, NY 14263

REFERENCES

(1.) Sunga AY, Oeffinger KC, Hudson MM, Mahoney MC. Care of cancer survivors. Am Fam Physician 2005; 71:699-706.

(2.) National Comprehensive Cancer Network. The NCCN clinical practice guidelines in oncology. Accessed online June 13, 2005, at: http//www.nccn.org/professionals/ physician_gls/default.asp.

(3.) Sargent DJ, Wieand S, Benedetti J, Labianca R, Haller DG, Shepherd LE, et al. Disease-free survival (DFS) vs. overall survival (OS) as a primary endpoint for adjuvant colon cancer studies: individual patient data from 12,915 patients on 15 randomized trials. J Clin Oncol 2004;22(14S):3502.

(4.) Chau I, Allen MJ, Cunningham D, Norman AR, Brown G, Ford HE, et al. The value of routine serum car-cino-embryonic antigen measurement and computed tomography in the surveillance of patients after adjuvant chemotherapy for colorectal cancer. J Clin Oncol 2004;22:1420-9.

(5.) Tepper JE, JE, O'Connell M, Hollis D, Niedzwiecki D, Cooke E, Mayer RJ. Analysis of surgical salvage after failure of primary therapy in rectal cancer: results from Intergroup Study 0114. J Clin Oncol 2003;21:3623-8.

(6.) Jeffery GM, Hickey BE, Hider P. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev 2002;(1):CD002200.

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