Endoscopic surveillance after resection of sessile serrated lesions: so far, so good?

Polyp detection is on the rise! Since the establishment of the adenoma detection rate (ADR) as the primary quality parameter in colonoscopy [1], we have been focusing on improving our ability to detect colorectal adenomas, both through the refinement of our techniques and the growing availability and use of technological means that enhance detection capabilities. This increased awareness of the importance of meticulous mucosal inspection and the incorporation of quality assurance programs, including benchmarking, auditing, and retraining, have led to an increase in mean ADR across endoscopists and have played a decisive role in the global improvement of colonoscopy quality. However, we have also learned that not all that glitters is gold – ADR is not perfect! As a surrogate rather than direct measure of colonoscopy efficacy, it is suspectable to gaming (“one adenoma and done”) and may not reflect the colorectal cancer (CRC) risk for the individual patient or their need for surveillance colonoscopy. Indeed, up to 30 % of all CRCs appear to arise from the serrated neoplasia pathway rather than the conventional adenoma–carcinoma sequence. This raises doubts about the protective effects of a high ADR among this relatively large proportion of patients.

“The use of total metachronous advanced neoplasia, which includes serrated lesions in the metachronous neoplasia calculation, could give a more comprehensive estimate of the post-polypectomy risk for an individual patient…”

Sessile serrated lesions (SSLs) have gained increased attention in recent years as important precursors of CRC. These lesions are considered to be more difficult to identify and their subtle borders can lead to reduced certainty about whether their removal has been complete. Moreover, histopathological interobserver agreement for differentiating among SSL subtypes is known to be low [2]. In addition, the spectrum of SSLs is broad, ranging between hyperplastic polyps, at close-to-zero malignant potential, to large, proximal, sessile serrated adenomas with dysplasia, considered at high risk for CRC transformation [2]. In the coming years, the SSL detection rate is expected to rise as their importance is increasingly recognized and general lesion detection capabilities improve. In addition, recent evidence has suggested an inverse relationship between proximal SSL detection rate and post-colonoscopy CRC incidence, independently from ADR levels [3]. This will probably result in increased SSL detection efforts, and even in the addition of this parameter to the required quality thresholds defined by scientific societies [4].

An increase in SSL detection comes hand in hand with an increase in endoscopic surveillance following SSL removal. How will we deal with this? The optimal surveillance interval for patients with SSLs remains uncertain. A paucity of evidence results in variability of surveillance interval recommendations between different guidelines, with intervals spanning 1, 3, and 10 years for somewhat similar scenarios [5] [6].

The actual risk of metachronous CRCs in patients with SSLs compared with patients without SSLs is unknown. SSLs are strongly associated with smoking, alcohol consumption, and even obesity, all independent risk factors for CRC [2], and thus could be proxies of poorer health status in general rather than independently associated with an increase in cancer risk. In addition, surveillance interval recommendations for SSLs have been drawn from adenoma surveillance intervals rather than tailored on SSL specificities and might not be appropriate. Indeed, some have argued that SSL surveillance intervals are too aggressive, as they mirror adenoma surveillance intervals, while others argue that the pathway to CRC of SSLs may see an acceleration at a certain point, advocating an even more aggressive strategy for patients with SSLs considered at higher risk [2]. Whatever the case, the increase in SSL detection will bring more surveillance pressure on already overstretched endoscopy services, and there is an urgent need for substratification to identify which SSLs actually deserve increased surveillance.

In this issue of Endoscopy, Djinbachian et al. present a large retrospective matched case–cohort analysis of the prevalence of total metachronous advanced neoplasia (T-MAN) among patients who underwent resection of an SSL compared with patients without SSLs [7]. T-MAN is an “umbrella” outcome that includes both metachronous advanced adenomas and metachronous advanced SSLs. The authors found a significant higher prevalence of T-MAN at surveillance colonoscopy among patients who underwent removal of a proximal SSL ≥ 10 mm, a proximal SSL < 10 mm, but not distal SSLs (of any size) at baseline colonoscopy. Interestingly, they also found that T-MAN in patients with SSLs was mainly driven by high rates of subsequent SSLs rather than by a large increase in metachronous advanced adenomas.

These findings could have distinct clinical implications. The use of T-MAN, which includes serrated lesions in the metachronous neoplasia calculation, could give a more comprehensive estimate of the post-polypectomy risk for an individual patient, as many previous studies only focused on metachronous adenomas/advanced adenomas. However, this may misjudge metachronous neoplastic risk for some patient groups, exposing them to excessive risks related to under-surveillance. On the other hand, as the increased T-MAN prevalence in patients with baseline SSLs was driven mainly by metachronous SSLs, whose risk and timing of cancer development are still uncertain, the impact of increased surveillance on CRC incidence and mortality in patients with baseline SSLs is still completely unknown and may result in over-surveillance related to this over-diagnosis. As no strong data showing the actual efficacy of SSL surveillance on hard outcomes have been published to date, even less is known about the impact of removing metachronous SSLs on future development of CRC. This broad surveillance approach for SSLs may be an ineffective way of pursuing markers of overall poor health without having a significant impact on patient outcomes. Potentially, it could be more beneficial to target specific populations carrying an increased CRC risk.

It is important to note that metachronous neoplasia is an intermediate outcome, hierarchically inferior to harder outcomes such as CRC incidence and mortality. It is very much conceivable that for SSLs we will go through the same milestones that were crossed when recommending surveillance after the removal of adenomas. Indeed, in the past 10 years, many histological risk factors of adenomas have been questioned and reprioritized toward a more conservative use of surveillance, as larger studies analyzing the independent impact of every risk factor on CRC incidence and mortality have become available [8]. We also expect even more insights and further repurposing of surveillance resources when the results of ambitious and well-designed randomized controlled trials on polyp surveillance are published later this decade [9].

For SSLs, we must temporarily accept the intrinsic limitations and choose the most appropriate surveillance interval based on the intermediate outcome information we have, and in this respect, well-designed large retrospective analyses such as the one by Djinbachian et al. are most welcome in providing us with clinically useful information to guide choices in the best interest of patients. At the same time, we must patiently await studies that deliver stronger evidence on the CRC risk of patients who undergo removal of SSLs, and on how active surveillance may impact their prognosis. Furthermore, as a community, endoscopists should still strive toward undertaking prospective studies that can help us provide definitive answers to patients and colleagues alike in the complex task of SSL management.

Publication History

Article published online:
12 May 2023

• References

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