In patients with ulcerative colitis (UC), primary sclerosing cholangitis (PSC) is one of the strongest risk factors for colorectal neoplasia. Although PSC affects only a minority of patients with inflammatory bowel disease, its coexistence with UC substantially alters the natural history of colorectal carcinogenesis. Evidence from Europe and North America has consistently shown that patients with concomitant PSC and UC develop colorectal neoplasia at a younger age, after a shorter disease duration, and with a higher lifetime risk than patients with UC alone [1].
These observations underpin current international guidelines, including those of the European Crohn’s and Colitis Organisation [2] and the British Society of Gastroenterology [3], both of which recommend initiating surveillance colonoscopy immediately after the diagnosis of PSC, regardless of UC duration. However, because these recommendations have been derived predominantly from Western populations, their applicability to Asian patients has remained uncertain.
In this issue of Intestinal Research, Komatsu et al. [4] reported a nationwide multicenter study supported by the Japanese Society for Cancer of the Colon and Rectum. By comparing the clinicopathological characteristics and long-term outcomes of UC-associated neoplasia (UCAN) in patients with and without PSC, this study provides the most comprehensive data on PSC-associated UCAN in Asia to date. Although the rarity of PSC inevitably limited the number of affected patients, this nationwide collaborative effort represents a substantial advance in our understanding of this unique high-risk phenotype in East Asian populations.
A notable strength of this study is its confirmation that the characteristic phenotype of PSC-associated UCAN previously described in Western cohorts is largely reproducible in Japanese patients. Patients with PSC developed colorectal neoplasia at a significantly younger age and after a shorter duration of UC, and neoplastic lesions occurred disproportionately in the right colon. These findings reinforce the concept that PSC is not merely a coincidental comorbidity but an independent modifier of colorectal carcinogenesis.
They provide important external validation of the clinicopathological phenotype of PSC-associated UCAN in Asian populations.
Notably, earlier development of colorectal neoplasia did not translate into poorer oncologic outcomes. Despite their younger age and shorter disease duration, patients with PSC were more likely to present with pathological stage 0–I disease, while cancer-specific survival remained comparable to that of patients without PSC. This pattern is more likely to reflect effective surveillance than intrinsic differences in tumor biology.
Most patients with available surveillance data had undergone colonoscopy within the preceding 2 years, suggesting that intensive surveillance at specialized Japanese centers may have contributed to the favorable stage distribution. Although the retrospective design precludes causal inference, the findings provide clinically meaningful support for regular surveillance colonoscopy in this high-risk population.
These findings have clinical implications that extend beyond colorectal cancer surveillance. Although cancer-specific survival was similar between the groups, overall survival was significantly lower in the PSC group among patients with pathological stage I–III disease. This gap was largely driven by liver-related complications rather than differences in colorectal cancer aggressiveness.
Indeed, deaths from biliary tract cancer and liver failure occurred only among patients with PSC, indicating that their long-term survival depends heavily on the course of liver disease as well as colorectal neoplasia. Therefore, surveillance colonoscopy should be integrated into a broader multidisciplinary framework involving gastroenterologists, hepatologists, surgeons, radiologists, pathologists, and liver transplant teams.
The findings should also be interpreted in the context of several important limitations. As a retrospective multicenter study spanning nearly four decades, temporal changes in endoscopic technology, pathological classification, surgical management, and medical therapy may have influenced both surveillance practices and clinical outcomes. Furthermore, only 26 patients with PSC-associated UCAN were identified, reflecting the rarity of PSC in East Asia.
Nevertheless, the nationwide design involving 43 institutions provides one of the most comprehensive datasets currently available for this uncommon but clinically important condition. In addition, because the cohort included only patients who had already developed UCAN, the study cannot estimate the cumulative risk of colorectal neoplasia among all patients with PSC-associated UC. Instead, its principal contribution lies in defining how colorectal neoplasia presents once it develops in this high-risk population.
This distinction is particularly relevant when interpreting Asian epidemiological data. In a Korean nationwide population-based study of 35,189 patients with UC [5], the incidence of colorectal cancer was not significantly increased among patients with PSC compared with the general population, whereas biliary cancer incidence was markedly increased. This apparent discrepancy may partly reflect the distinction between population-level colorectal cancer risk and the clinicopathological characteristics of UCAN once neoplasia has developed.
This study also suggests that the next challenge is no longer to establish whether PSC increases the risk of colorectal neoplasia, but rather to determine how surveillance strategies can be further individualized within this recognized high-risk population. One unresolved question concerns the timing of PSC diagnosis relative to the course of UC. Because PSC and UC follow distinct diagnostic pathways, the recorded sequence of diagnosis may not accurately reflect the biological disease onset.
Patients diagnosed with PSC routinely undergo colonoscopy to identify coexisting inflammatory bowel disease, whereas PSC in patients with established UC is often recognized only after cholestatic abnormalities in liver biochemical tests prompt further hepatobiliary investigation. Moreover, UC may remain clinically silent in some patients with PSC, allowing a substantial inflammatory burden to accumulate before formal diagnosis. Future studies should therefore determine whether the duration of UC at the time of PSC diagnosis, rather than the chronological order of diagnosis itself, better predicts subsequent colorectal neoplasia and facilitates individualized surveillance strategies.
Another priority is to refine risk stratification within the PSC population. Although current guidelines appropriately classify all patients with PSC-associated UC as high risk, they generally treat this population as a uniform group. The recent Japanese Society for Cancer of the Colon and Rectum guideline likewise identifies PSC as a risk factor for colorectal cancer in patients with UC, but the available evidence remains limited, particularly in the Japanese population [6].
Whether the risk of colorectal neoplasia varies according to PSC phenotype, disease severity, or progression remains largely unknown. Similarly, future research should determine whether favorable outcomes are primarily driven by surveillance intensity, surveillance quality, or both. Advances in high-definition colonoscopy, image-enhanced endoscopy, and artificial intelligence-assisted lesion detection may further enhance dysplasia detection during surveillance colonoscopy [7], but their incremental value in PSC-associated UC requires prospective evaluation.
In practice, optimizing surveillance will depend not only on identifying high-risk patients but also on consistently delivering high-quality examinations.
In conclusion, the nationwide Japanese study by Komatsu et al. [4] provides important evidence that the distinctive clinicopathological characteristics of PSC-associated UCAN in Western populations are also observed in Asian patients. These findings support current surveillance recommendations while highlighting opportunities to refine risk stratification and endoscopic quality. Future efforts should focus less on establishing PSC as a high-risk condition and more on optimizing surveillance strategies to improve early cancer detection while addressing the broader hepatobiliary burden of the disease.