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Routine Checks for Cancer Metastases: A Help or Harm?
Patients who have undergone a full course of curative-intent cancer treatment are often monitored for years with imaging scans and blood tests to identify recurrences early. For some solid tumors, scans are recommended as frequently as every 6 months over 5 years.
However, there are longstanding concerns about the value of surveillance after curative-intent cancer treatment in patients who remain asymptomatic.
The authors of a recent perspective in The New England Journal of Medicine questioned whether the common practice of scheduling scans and blood tests in symptom-free cancer survivors actually improves survival or quality of life.
Based on existing data, routine surveillance finds more recurrences but does not reduce mortality and often inflicts financial, physical, and psychological harm, H. Gilbert Welch, MD, MPH, with the Center for Surgery and Public Health, Brigham and Women's Hospital, Boston, and Lesly A. Dossett, MD, MPH, from the Department of Surgery, University of Michigan, Ann Arbor, Michigan, concluded.
Therefore, 'less surveillance would be better for patients,' Welch and Dossett wrote.
Kathy D. Miller, MD, co-director of the Breast Cancer Program at Indiana University Health Simon Cancer Center, Indianapolis, told Medscape Medical News that she 'wholeheartedly' agrees and noted that this topic was the focus of the very first Choosing Wisely campaign.
Miller cautioned, however, that the extent of surveillance in this patient population is a question that constantly needs to be reasked.
'As either the technology or, more importantly, the available treatments improve, the answer may change,' she said. But 'we are not there yet, and doing the tests in the absence of that evidence has the real potential for harm.'
What Do Guidelines Say?
A consistent theme across specialty societies that participate in the Choosing Wisely campaign, including the American Society of Clinical Oncology (ASCO), is to avoid ordering imaging scans (PET, CT, or bone scans) or blood-based tumor-marker tests as part of routine follow-up care for asymptomatic patients after curative cancer treatment for solid tumors unless strong evidence shows that the testing leads to improved survival or quality of life.
Current guidelines typically endorse routine surveillance in these patients, but the benefits are often not clear.
For colon cancer, despite the latest data showing no survival benefit, guidelines uniformly support routine surveillance with imaging after curative treatment, though the recommended schedule varies. For prostate cancer, annual prostate-specific antigen testing is recommended after curative-intent treatment despite the high 20-year survival rate.
For non-small cell lung cancer, all major guidelines recommend routine imaging surveillance following curative-intent surgery, though the interval varies as well. How ever, the evidence to date does not show an overall survival benefit with routine surveillance in this population, according to Brooke E. Wilson, MBBS, from the Department of Oncology at Queen's University, Kingston, Ontario, Canada, and co-authors in a recent review of the evidence.
For pancreatic cancer, guidelines are inconsistent, given the lack of randomized data to support surveillance. The National Comprehensive Cancer Network (NCCN), for instance, recommends routine CT chest, abdomen, and pelvis surveillance every 3-6 months for 2 years, and then every 6-12 months after, while the European Society for Medical Oncology highlights the lack of evidence to support regular imaging surveillance.
For breast cancer, however, ASCO and NCCN recommend against routine surveillance for metastatic disease in asymptomatic patients. Even so, some studies suggest that, in practice, many physicians may still order imaging, including chest radiographs, MRI, PET, CT, or bone scans.
What's the evidence in favor of routine surveillance in asymptomatic patients?
In their perspective, Welch and Dossett explain that the theoretical case for routine cancer surveillance is 'strong.'
Tumor burden will likely be lower before symptoms of recurrence develop, and treatment is expected to be more effective when a recurrence is detected at an earlier stage. Some data appear to back up this argument, showing that 5-year survival rates are higher among patients with asymptomatic vs symptomatic recurrences.
But there's a caveat, Welch and Dossett cautioned. When recurrences are detected earlier in patients who are asymptomatic, survival will always appear to be longer than when recurrences are detected clinically simply because the 'survival clock' starts sooner (classic lead-time bias). Only randomized controlled trials (RCTs) that randomize patients before recurrence can give an unbiased answer.
Despite the theoretical case for routine cancer surveillance, the empirical case is 'weak,' according to Welch and Dossett.
A case in point: Among 12 RCTs of imaging-based surveillance across several solid tumors that were included in a 2021 systematic review, none found a statistically significant mortality benefit in asymptomatic patients. In a 'coin flip' pattern, the risk for death was slightly lower in the surveillance group in six of the trials and slightly lower in the control group in the other six trials.
Although routine surveillance is common in practice, 'these findings suggest that detection and treatment of asymptomatic cancer recurrences offers no advantage over initiation of treatment only after symptoms develop,' Welch and Dossett concluded.
However, Mark A. Lewis, MD, director of Gastrointestinal Oncology at Intermountain Healthcare, Salt Lake City, noted that when it comes to surveillance in asymptomatic patients, he doesn't think there is necessarily a 'one-size-fits-all approach to all cancers.'
'Speaking from personal experience, surveillance allowed me to catch my own pancreas changing 'in time' for a surgery that — to date — has postponed or prevented metastasis to my liver,' Lewis explained, with the caveat that he has a hereditary condition that calls for annual surveillance.
In addition to genetics, cancer type may matter as well.
'From a lung-cancer standpoint, the statement that surveillance does more harm than good is inaccurate,' Raja M. Flores, MD, chairman of Thoracic Surgery, Mount Sinai Health System, New York City, told Medscape Medical News .
In his experience, because lung cancer progresses quickly, early detection changes outcomes dramatically. 'Lung cancer kills you so quickly, so that when you catch it early, you really have that window of opportunity to cut it out and cure the patient,' Flores said.
But, he added, 'in lung cancer, routine surveillance is aimed largely at detecting second primary tumors, not simply recurrences, because having a prior history of lung cancer means that you are at higher risk of developing a second lung cancer.'
What's the harm of routine surveillance in asymptomatic patients?
In the US, there are now roughly 18 million cancer survivors who are potential targets for ongoing surveillance. 'Although it is tempting to believe that surveillance for metastases can only help people with cancer, the harms are evident,' Welch and Dossett wrote.
Chief among them: Surveillance scans and blood tests may provoke anxiety, fuel fears of recurrence, and expose patients to further investigations from incidental findings, which can boost radiation exposure. Surveillance also takes time away from work and family, and the costs are increasingly borne by patients themselves.
'We believe it's unlikely that patients would opt to undergo routine surveillance…if they were informed about the absence of a mortality benefit' and about the potential for financial, physical, and psychological harms, Welch and Dossett said.
Patients who are currently sick and suffering can benefit from medical interventions, but 'for asymptomatic patients, the implied promise is that testing will help prevent deaths in the future,' Welch and Dossett wrote. And 'there is an ethical imperative to ensure that this implied promise is genuine.'
The authors of a recent Comments and Controversies perspective article in the Journal of Clinical Oncology also voiced concern that the risk-benefit ratio of routine surveillance imaging is 'not adequately considered by many practice guidelines, nor is it routinely discussed with patients.'
Decisions about surveillance imaging after curative intent cancer treatment should be 'patient-centered,' Wilson and co-authors wrote.
While surveillance imaging may be appropriate for some patients, 'the onus is on clinicians to critically evaluate guideline recommendations and to clearly communicate the harms vs benefits of routine surveillance to patients,' Wilson and colleagues advised.
Will Liquid Biopsies Change the Risk-Benefit?
Testing for minimal residual disease via circulating tumor DNA (ctDNA), which is now becoming more mainstream in solid tumors, 'is arguably making a difference in both the psychological and physical aspects of follow-up,' Lewis said.
There is evidence that minimal residual disease testing may reduce patient apprehension. And a recent study from Japan supports the utility of serial monitoring of ctDNA after curative-intent colorectal cancer resection, Lewis noted.
Welch and Dossett think ctDNA from the original tumor during surveillance will likely constitute a 'highly specific finding, providing powerful evidence that a cancer has come back. But whether detection of molecular recurrences helps patients live longer or live better is a question that has yet to be answered — and one that can be addressed only with an RCT.'
Welch and Dossett call on regulators and policymakers to 'raise the bar' for approving new blood-based biomarker tests and require that trials measure not just analytic validity (does a test detect ctDNA accurately?) but also clinical utility (does it help patients live longer or better?).
Although detecting minimal residual disease through ctDNA testing offers 'new opportunities for noninvasive surveillance, early detection, and potentially early interventions,' widespread adoption as a surveillance strategy 'should be discouraged' until randomized data demonstrate that early treatment of minimal residual disease leads to improved survival or quality of life for patients, Wilson and colleagues concluded.
