The Future of Colorectal Cancer
The Future of Colorectal Cancer
The rise in incidence accompanied by a huge shift towards an earlier stage of CRC at diagnosis will have a major impact on clinical care in the near future. The increase in colonoscopies for selected asymptomatic patients will be coupled with an increase in therapeutic colonoscopies, as more lesions will be diagnosed that are amenable to endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). During recent years, EMR and ESD have emerged as therapeutic options for early-stage carcinomas of the upper gastrointestinal tract and recently also for advanced lesions of the colon. Compared with surgery, these endoscopic techniques have considerable morbidity and mortality benefits. Histological assessment of selected lesions is as accurate as with surgical resection, as ESD allows en bloc resection of large lesions. However, larger, flat laterally spreading lesions are often still referred for surgery, although the majority of these lesions could also be treated with EMR or ESD. As experience with ESD in European countries is still limited, the current challenge is to improve and standardise training for this technique in the Western World. Endoscopists competent in EMR/ESD of the colon are mainly trained in Japan, which advocates for a close collaboration between European and Asian centres over the next decade. Furthermore, studies comparing different equipment and techniques for selecting the optimal method and standardising the performance of the procedures to improve ESD training and patient outcome are needed. Therefore, emphasis should be on risk stratification, early recognition of complications, and complication management. A combined technique of circumferential submucosal incision with EMR seems a promising approach. It potentially enhances en bloc resection with EMR and decreases procedure time for ESD.
The risk of undertreatment by intraluminal resection of curable patients should be prevented by optimal and adequate staging and disease profiling. Lymph node metastases (LNMs) must be ruled out before a lesion can be cured by endoscopic treatment. Therefore new imaging techniques to accurately detect LNMs are warranted. Currently, endoscopic treatment of non-pedunculated T1 lesions is limited to lesions with a maximal depth of invasion of <1000 μm into the submucosa, without vessel involvement and which are well or moderately differentiated. However, the majority of more deeply infiltrating T1 lesions could also be cured with endoscopic treatment, as only 10–15% of these patients will have LNMs. Moreover, patients fulfilling these criteria do not have a zero risk of LNMs. With the expected rise in T1 lesions, it will become more important to improve the identification of patients with or without LNMs. Hence, patients can be cured by endoscopic treatment only. New imaging techniques are being developed. With optical coherence tomography (OCT), cross-sectional images of the colorectal mucosa and submucosa can be made by looking at how light propagates in tissue and how it is scattered by tissue structures. Recent developments make this a promising technique for measurement of infiltration depth and direct in situ analysis of nodal status, as well as for increasing the sensitivity of the detection of malignant lesions in the colon (eg, during follow-up colonoscopy after an initial positive FIT test). By detecting both the intensity and polarisation state of the light, tissue-specific contrast is enhanced. Compared with endoscopic ultrasound, OCT provides greater contrast, which increases the ability to detect tumour margins, although the penetration depth of the signal is currently limited to 2–3 mm. The introduction of so-called spectral domain OCT has made this technique faster and applicable for looking at large areas with a microscopic resolution (<10 μm), which has been demonstrated in the detection of metaplasia and dysplasia in the oesophagus. Furthermore, the anatomical pictures of OCT can be complemented by fluorescent labelled micro-particles to give molecular insight into the mucosa.
These developments are expected to improve rapidly and will extend indications for EMR and ESD to remove early lesions in the colon, thereby reducing the need for invasive surgical procedures. In addition, transluminal endoscopic microsurgery (TEM) and natural orifice transluminal endoscopic surgery (NOTES) allow minimal invasive transmural full-thickness excision at sites in the rectum and proximal to the rectum, respectively. Again, improvements in preoperative staging are key to selecting T1/T2-N0 patients who do not need radical mesenteric resection to further improve outcome.
Challenge I: To Improve Minimal Invasive Resection Techniques and Identification of Regional Lymph Node Metastases
The rise in incidence accompanied by a huge shift towards an earlier stage of CRC at diagnosis will have a major impact on clinical care in the near future. The increase in colonoscopies for selected asymptomatic patients will be coupled with an increase in therapeutic colonoscopies, as more lesions will be diagnosed that are amenable to endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). During recent years, EMR and ESD have emerged as therapeutic options for early-stage carcinomas of the upper gastrointestinal tract and recently also for advanced lesions of the colon. Compared with surgery, these endoscopic techniques have considerable morbidity and mortality benefits. Histological assessment of selected lesions is as accurate as with surgical resection, as ESD allows en bloc resection of large lesions. However, larger, flat laterally spreading lesions are often still referred for surgery, although the majority of these lesions could also be treated with EMR or ESD. As experience with ESD in European countries is still limited, the current challenge is to improve and standardise training for this technique in the Western World. Endoscopists competent in EMR/ESD of the colon are mainly trained in Japan, which advocates for a close collaboration between European and Asian centres over the next decade. Furthermore, studies comparing different equipment and techniques for selecting the optimal method and standardising the performance of the procedures to improve ESD training and patient outcome are needed. Therefore, emphasis should be on risk stratification, early recognition of complications, and complication management. A combined technique of circumferential submucosal incision with EMR seems a promising approach. It potentially enhances en bloc resection with EMR and decreases procedure time for ESD.
The risk of undertreatment by intraluminal resection of curable patients should be prevented by optimal and adequate staging and disease profiling. Lymph node metastases (LNMs) must be ruled out before a lesion can be cured by endoscopic treatment. Therefore new imaging techniques to accurately detect LNMs are warranted. Currently, endoscopic treatment of non-pedunculated T1 lesions is limited to lesions with a maximal depth of invasion of <1000 μm into the submucosa, without vessel involvement and which are well or moderately differentiated. However, the majority of more deeply infiltrating T1 lesions could also be cured with endoscopic treatment, as only 10–15% of these patients will have LNMs. Moreover, patients fulfilling these criteria do not have a zero risk of LNMs. With the expected rise in T1 lesions, it will become more important to improve the identification of patients with or without LNMs. Hence, patients can be cured by endoscopic treatment only. New imaging techniques are being developed. With optical coherence tomography (OCT), cross-sectional images of the colorectal mucosa and submucosa can be made by looking at how light propagates in tissue and how it is scattered by tissue structures. Recent developments make this a promising technique for measurement of infiltration depth and direct in situ analysis of nodal status, as well as for increasing the sensitivity of the detection of malignant lesions in the colon (eg, during follow-up colonoscopy after an initial positive FIT test). By detecting both the intensity and polarisation state of the light, tissue-specific contrast is enhanced. Compared with endoscopic ultrasound, OCT provides greater contrast, which increases the ability to detect tumour margins, although the penetration depth of the signal is currently limited to 2–3 mm. The introduction of so-called spectral domain OCT has made this technique faster and applicable for looking at large areas with a microscopic resolution (<10 μm), which has been demonstrated in the detection of metaplasia and dysplasia in the oesophagus. Furthermore, the anatomical pictures of OCT can be complemented by fluorescent labelled micro-particles to give molecular insight into the mucosa.
These developments are expected to improve rapidly and will extend indications for EMR and ESD to remove early lesions in the colon, thereby reducing the need for invasive surgical procedures. In addition, transluminal endoscopic microsurgery (TEM) and natural orifice transluminal endoscopic surgery (NOTES) allow minimal invasive transmural full-thickness excision at sites in the rectum and proximal to the rectum, respectively. Again, improvements in preoperative staging are key to selecting T1/T2-N0 patients who do not need radical mesenteric resection to further improve outcome.