Intensive Surveillance After Stage II or III Colorectal Cancer: Is It Worth It?

After treatment for a newly diagnosed stage II or III colorectal cancer, the patient— hoping the worst is over—focuses on restored physical vigor and self confidence while resuming pre-illness roles. Meanwhile, practitioners focus on orchestrating patient follow-up, knowing that some 30% to 40% will recur or develop a second bowel cancer. Most residual disease will manifest itself as recurrence within 3 years, and almost all cases will be diagnosed within 5 years of initial diagnosis. How good is the evidence for choosing what follow-up examinations to order? For years, prevailing wisdom was that early recurrence detection, including for colorectal cancers, is seldom useful. In this scenario, intensive testing leads to anxiety, financial burden, and seldom changes disease outcomes. In that circumstance, waiting for signs or symptoms, rather than detecting early disease manifestations is defensible, albeit somewhat paternalistic. Arguably, we spare patients the knowledge that they have a lethal disease and can husband scarce resources. However, for many discerning patients and physicians, particularly with respect to colorectal cancer, this minimalist approach has never been intellectually satisfying. Physical examination virtually never discerns early hepatic, lung, or anastomotic recurrence and carcinoembryonic antigen (CEA) is only elevated in 60% of patients with recurrence. Waiting for signs and symptoms seems contrary to instincts in life and medicine that early detection and prompt disease management is best. Also, despite the suspicion that tumor cells are embolic to many sites, some colorectal cancer patients develop a single or a few metastases, some amenable to curative surgical resection. Fong reported that a subset of 1,001 patients at Memorial SloanKettering Cancer Center with a single liver metastasis resected had cure rates as high as 60%. Other series have noted that lung lesions, as well as recurrence at the site of colonic anastamosis and second primary tumors, were potentially curable. With more effective chemotherapy and biologic therapies for colorectal cancer, the potential for cure with medical therapy alone, a singularly elusive end point in the past, may have come within reach. In the North Center Cancer Treatment Group N9741 study, patients with advanced colorectal cancer were randomly assigned to folinic acid, fluorouracil (FU), and oxaliplatin (FOLFOX), irinotecan, FU, and leucovorin (IFL), or irinotecan and oxaliplatin (IROX). Approximately 11% of patients treated with FOLFOX, of whom only a minority underwent resection, are alive at 4 years, suggesting that patients with metastatic disease may be long-term survivors with chemotherapy alone (unpublished data). These combined advances in diagnostics and treatments suggest early detection of recurrence could translate into a second chance for cure for some patients faced with recurrent or metastatic cancer. In 2000, the American Society of Clinical Oncology (ASCO) convened experts to make evidence-based recommendations on follow-up. Their conclusion was that periodic clinical evaluations with CEA testing and colonoscopy were justifiable, but that other testing added little additional benefit. Despite this recommendation, we all have anecdotal triumphs in our practices of relapsed patients cured when recurrent disease was extirpated, and want more such happy endings and the best and most efficient way to turn anecdotes into standard practice. Randomized trials of more intensive versus less intensive follow-ups have been hard to conduct, forcing decisions based on retrospective reviews and metaanalyses. Additionally, the continuous improvement in diagnostic and treatment technology suggests the need for reassessment of best strategies. In this setting, Rodriguez-Moranto et al report the results of their randomized trial of two different follow-up strategies in this issue. Their study enrolled 259 stage II or III colorectal cancer patients from three hospitals in Catalonia. Their simple strategy included medical history, physical examination, CBC, liver function tests, and CEA. Their intensive strategy included the simple strategy methods plus abdominal computed tomography (CT) or ultrasound imaging, chest x-ray, and colonoscopy. Work-up for signs or symptoms of recurrent disease was comparable in both study arms. After a median follow-up of 4 years from diagnosis, there is no significant survival difference between the two strategies (hazard ratio [HR] 0.87, P .62). In subset analysis, the 76 intensive strategy patients with stage II colon cancer (HR 0.34, P .045) and the 29 with rectal cancer (HR 0.09, P .03) had a survival advantage over the simple strategy stage II groups. In those patients with recurrence on the intensive strategy 51% (18 of 35) were amenable to resection compared to 29% (10 of 34) in the simple strategy. The Rodriguez-Moranto et al study has strengths and weaknesses, some of which are acknowledged in their discussion. By conducting the study in three institutions, the authors limited the number of participating radiologists, gastroenterologists, medical oncologists, and surgeons. The ineligibility rate was minimal and no patients were lost to follow-up. The analysis is carefully done JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 24 NUMBER 3 JANUARY 2