Is there a role for endoscopic management of the large bowel in familial adenomatous polyposis?

In this issue of Endoscopy, Ishikawa et al. [1] describe intense endoscopic downstaging of colorectal polyp burden in patients with familial adenomatous polyposis (FAP) in a multicenter, prospective, interventional study. After 5 years, 90.4 % of patients with intact colon remained without surgical intervention and 83.9 % of those who had 10 cm or more residual large bowel did not require further surgical intervention. The authors conclude that their approach “could have the potential to be a useful means of preventing colorectal cancer without implementing colectomy.” This raises interesting questions about the role of endoscopy in the management of FAP and perhaps can be seen to challenge the paradigm of surgical management of this condition, in all except those with a very mild polyp burden.

Before the development of safe anesthesia, surgery in FAP was reserved for cases with colorectal cancer (CRC); CRC was the main cause of death, occurring usually in the fifth decade of life. With the advent of safe prophylactic surgery, life expectancy rose dramatically almost to the level of the general population [2]. For those with an intact large bowel, any management strategy will need to be compared with the undoubted benefit of such surgical intervention, the key outcome being CRC prevention. For those who have already undergone colectomy and ileorectal anastomosis (IRA) or indeed a subtotal colectomy, the end points include not only CRC but also need for secondary proctectomy.

“The data in this study, however, do not provide justification for a long-term endoscopic approach to the management of the large bowel for those with a more standard polyp burden. However, it may be a useful short-term option, for example to allow a patient to adjust to the need for surgery.”

If we first concentrate on the patients with an intact large bowel, which is the group where this approach will be most contentious, the study group is very heterogeneous, with a wide age range, including 12.7 % aged ≥ 50 years; 12.7 % of this group are also stated as having had previous CRC but no surgical intervention. Therefore, this is not representative of most patients with FAP.

The burden of colonoscopy is significant, with 86.1 % undergoing five or more colonoscopies and 19.9 % undergoing nine or more colonoscopies over 5 years. The mean number of polypectomies exceeds 500 and 19.9 % had over 900 polypectomies. Despite this extraordinary intensive approach by expert endoscopists, two patients developed CRC, diagnosed 160 and 181 days after their last procedures. CRC stage and outcomes are not commented upon. Although this represents only 1.2 % of the group, both CRCs were entirely preventable. High grade dysplasia (HGD) or intramucosal carcinoma (IMC) was detected on one or more occasions during follow-up in 21.1 %, highlighting the high risk of this cohort. Endoscopic complications were few: two perforations and three post-polypectomy bleeds. The sustainability of this approach in the long term is not demonstrated as the study period was only 5 years, yet the condition requires life-long management.

The group who had undergone prior surgery included any surgery, which meant that there was 10 cm or more of large bowel remaining. Therefore, colectomy and IRA, segmental, and extended segmental resections are all included, making interpretation of the findings challenging. The number of endoscopic procedures and polypectomies were fewer than for those without prior surgery, as one would expect. It is an older patient group, yet there were still patients aged in their twenties who had over 100 adenomas in the residual colorectum following surgery. It is very difficult to elucidate the surgical decision making in this group but the fact that 46/56 had undergone colectomy and IRA does highlight the importance of personalizing surgery based on colonic and rectal phenotype [3]; restorative proctocolectomy may have been more suitable in a number of these patients.

Most of this group had undergone colectomy and IRA, a familiar clinical scenario. Published data indicate that with endoscopic surveillance and polypectomy, long-term rectal preservation without cancer developing is possible [4] [5]. There is a clear rationale for trying to avoid secondary proctectomy with the inherent complications related to pelvic dissection and the need for a stoma or ileoanal pouch, which adversely impact quality of life. However, this is on the proviso that it is safe to do so and that cancer can be avoided. In this study, one patient underwent proctectomy for multifocal IMC. A further seven patients had HGD or IMC on more than one occasion yet did not undergo surgery; invasive CRC did not develop. 

How should we interpret these study data? Do they change current approaches to management in FAP? The authors are not advocating primary endoscopic management for all patients with FAP and the patients in this study had declined surgery.

There is no doubt that there have been advances in endoscopic diagnostic and therapeutic capabilities. Primary endoscopic management may be considered for those with a very mild polyp burden, and this seems justified. The data in this study, however, do not provide justification for a long-term endoscopic approach to the management of the large bowel for those with a more standard polyp burden. However, it may be a useful short-term option, for example to allow a patient to adjust to the need for surgery. There will be exceptions, where there is a compelling clinical reason to delay surgery for as long as possible, for example those in whom there is a high risk of development of desmoid tumors. However, even in this group, deferring surgery is only done while it is felt that the risk of developing CRC is minimal. This study would indicate that for this group, perhaps a more aggressive endoscopic approach could be adopted.

For those who have undergone surgery previously, these data support the current literature in that an endoscopic approach to the management of the rectum is feasible and safe, both in terms of endoscopic complications but from a cancer prevention perspective too.

Personalized care is a fundamental concept underpinning the management of FAP. Management of the large bowel, timing of surgery, and extent of surgery are major clinical decisions that need to be made. With increasing endoscopic capabilities and progressive refinement of surgical decision making, such cases are best managed in specialist centers to optimize both clinical decision making and patient outcomes.

Publication History

Article published online:
26 January 2023

• References

• 1 Ishikawa H, Yamada M, Sato Y. et al. Intensive endoscopic resection for downstaging of polyp burden in patients with familial adenomatous polyposis (J-FAPP Study III): a multicenter prospective interventional study. Endoscopy 2023; 55: 344-352 DOI: 10.1055/a-1945-9120.
• 2 Nugent KP, Spigelman AD, Phillips RK. Life expectancy after colectomy and ileorectal anastomosis for familial adenomatous polyposis. Dis Colon Rectum 1993; 36: 1059-1062
• 3 Sinha A, Tekkis PP, Rashid S. et al. Risk factors for secondary proctectomy in patients with familial adenomatous polyposis. Br J Surg 2010; 97: 1710-1715
• 4 Anele CC, Xiang J, Martin I. et al. Regular endoscopic surveillance and polypectomy is effective in managing rectal adenoma progression following colectomy and ileorectal anastomosis in patients with familial adenomatous polyposis. Colorectal Dis 2022; 24: 277-283
• 5 Pasquer A, Benech N, Pioche M. et al. Prophylactic colectomy and rectal preservation in FAP: systematic endoscopic follow-up and adenoma destruction changes natural history of polyposis. Endosc Int Open 2021; 9: E1014-E102