TEMS vs RR for lower rectal cancer
M. S. Sajid et al.
Commentary on Sajid et al. Bowel cancer screening provides an opportunity to re-evaluate the therapeutic strategy for rectal cancer. In recent years there has been a rapid reduction in rectal cancer disease-associated mortality, but treatmentrelated morbidity and mortality remain high [1,2]. Long-term bowel, bladder and sexual dysfunctions are frequent complications of radical surgery for rectal cancer [3,4]. Permanent stomas are required in perhaps one-fifth of cases. The 30-day mortality for all rectal cancer surgery performed within the UK National Health Service (NHS) is 4.6% [5]. Screening using the faecal occult blood test (FOBT) identifies a high proportion of cases of rectal cancer at an early stage. In 2009, approximately 25% of the UK’s 13 970 newly diagnosed rectal tumours were Dukes A (T1/2N0). Incorporation of flexible sigmoidoscopy, a more sensitive tool than FOBT, into the national screening programme from 2014 will further promote early diagnosis [6]. Although Dukes A tumours are generally small and localized, standard treatment dictates removal of the entire organ by radical surgery. Radical surgery achieves complete rectal and mesorectal excision, providing definitive information about the T stage and local nodal metastasis. If no involved nodes are found then there is little risk of regional recurrence and a diminished risk of systemic relapse. There is no lymph node involvement (N0) in 80–85% of T1 and T2 rectal cancers [7]. Hence, routine lymph node dissection in these patients is over-treatment and could potentially be avoided. In the present issue of Colorectal Disease, Sajid et al. [8] have examined this contentious area. They performed a meta-analysis of 942 cases from 10 studies, comparing conventional treatment of pT1 and pT2 rectal cancer by radical surgery with an organpreserving approach using either transanal endoscopic microsurgery (TEMS) or chemoradiation followed by TEMS. Five papers contained a randomized comparison and the other five employed retrospective case controls. The authors acknowledge that the quality of all studies was only moderate to low at best. Heterogeneous case selection through diverse entry criteria was a particularly prominent issue. Historically, organpreserving techniques were utilized in patients who displayed signs of increased frailty and comorbidity relative to the general population. Cultural attitudes to stomas are also known to produce regional variation in practice. Two primary outcome measures were considered: overall survival and local recurrence. The authors concluded that there was no difference in distant recurrence
doi:10.1111/codi.12494
and overall survival between the two treatments, but the risk of local recurrence was higher following TEMS (OR = 2.78; 95% CI: 1.42–5.44). These results are perhaps in keeping with our preconceptions. Transanal endoscopic microsurgery alone is unlikely to be oncologically superior to radical surgery for the treatment of low rectal cancer. In particular, one would not expect stand-alone TEMS to be effective in patients with occult N+ disease. The precise proportion of N+ cases is difficult to judge, especially in our screendetected population. We would expect the overall rate to be low, and preoperative evaluation of suitability for TEMS, using endoscopy, biopsy, high-quality MRI and endorectal ultrasound (ERUS) will further bias against N+ disease. Nevertheless, some cases will evade detection, confounding subsequent comparison of the outcome of TEMS (T1-2 Nx) and radical surgery (T1-2N0), otherwise known as the Will Rogers effect. Occult nodal disease is not the only potential cause of recurrence following TEMS. We should also consider the possibility that tumour cells may be shed from the TEMS specimen and implant within the surgical wound. Mechanical washouts may reduce this risk, although their efficacy is unproven. Differentiating luminal from nodal recurrence may give a clue to the dominant mechanism of treatment failure to inform refinement of organ-preserving techniques particularly with regard to the use of contact radiotherapy. Following TEMS, a strategy of regular surveillance with MRI and endoscopy aims to identify local treatment failure in time for salvage surgery to be successful. This stepwise escalation of treatment is an attractive concept as only those patients with recurrent, aggressive disease will have the organ excised. Historical cohort studies have cast doubt upon the efficacy of salvage, but they did not benefit from modern imaging technology [9]. In addition, the motivation to detect recurrence in elderly patients is sometimes reduced. Hypothetically, if organ preservation was associated with 10–15% local failure, approximating to a hazard ratio of 2.78 compared with radical surgery, and salvage rescued just 50%, the pathway would have failed to provide local disease control in 5.0–7.5% of cases. Meanwhile, the majority of patients would retain their rectum and avoid the 4.6% risk of perioperative mortality associated with radical surgery. At the opposite end of the disease spectrum, 12% of Dukes A cancers relapse systemically following radical surgery. As the metastatic event is likely to predate surgical treatment, and the method of resection is unlikely to alter outcome, radical surgery would not be optimal care.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 16, 2–16
15
TEMS vs RR for lower rectal cancer
M. S. Sajid et al.
The future success of organ preservation hinges upon developing treatment pathways that can deliver low failure rates, combined with early detection and treatment of local failure. Cohort studies suggest that TEMS alone results in uncomfortably high rates of local failure across the spectrum of all T1 and T2 tumours [10]. This meta-analysis included a mixture of studies: some used TEMS alone and others employed neoadjuvant chemoradiation before TEMS to improve local control. Molecular stratification of early rectal cancer using pretreatment biopsies may help to discriminate high- and low-risk cases, thus enabling more objective deployment of radiotherapy [11]. Meanwhile the Cancer Research UK (CRUK) Transanal endoscopic microsurgery and Radiotherapy for Early rectal Cancer (TREC) study is currently randomizing patients with biopsy-proven, mriT1–2 rectal cancer of less than 3 cm in diameter to have conventional radical surgery or an organ-preserving protocol of short-course preoperative radiotherapy (5x5Gy) followed by TEMS 8–10 weeks later [12]. Radiotherapy aims to resolve occult N+ mesorectal disease and reduce shedding of tumour cells at the time of TEMS surgery. Data from such high-quality randomized controlled trials are needed if we are to be able to inform patients more precisely of the best treatment for early-stage rectal cancer. Although this is a challenging process, the goal of changing the management of rectal cancer makes it an exciting and worthwhile project.
S. P. Bach*† *University of Birmingham and †Queen Elizabeth Hospital Birmingham, Birmingham, UK E-mail: [email protected]
References 1 Tekkis PP, Poloniecki JD, Thompson MR, Stamatakis JD. Operative mortality in colorectal cancer: prospective national study. BMJ 2003; 327: 1196–201.
16
2 Rutten HJ, den Dulk M, Lemmens VE, van de Velde CJ, Marijnen CA. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol 2008; 9: 494–501. 3 Bryant CL, Lunniss PJ, Knowles CH, Thaha MA, Chan CL. Anterior resection syndrome. Lancet Oncol 2012; 13: e403–8. 4 Wallner C, Lange MM, Bonsing BA et al. Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the cooperative clinical investigators of the dutch total mesorectal excision trial. J Clin Oncol 2008; 26: 4466–72. 5 Morris EJ, Taylor EF, Thomas JD et al. Thirty-day postoperative mortality after colorectal cancer surgery in England. Gut 2011; 60: 806–13. 6 Atkin WS, Edwards R, Kralj-Hans I et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. The Lancet 2010; 375: 1624–33. 7 Chang HC, Huang SC, Chen JS et al. Risk factors for lymph node metastasis in pT1 and pT2 rectal cancer: a single-institute experience in 943 patients and literature review. Ann Surg Oncol 2012; 19: 2477–84. 8 Sajid MS, Farag S, Leung P, Sains P, Miles WFA, Baig MK. Systematic review and meta-analysis of published trials comparing the effectiveness of transanal endoscopic microsurgery (TEMS) and radical resection in the management of early rectal cancers. Colorectal Dis 2013; 16: 2–14. 9 Weiser MR, Landmann RG, Wong WD et al. Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum 2005; 48: 1169–75. 10 Bach SP, Hill J, Monson JR et al. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg 2009; 96: 280–90. 11 Leong KJ, Wei W, Tannahill LA et al. Methylation profiling of rectal cancer identifies novel markers of early-stage disease. Br J Surg. [Research Support, Non-U.S. Gov’t]. 2011; 98: 724–34. 12 TREC study. http://www.controlled-trials.com/isrctn144 22743 (accessed 25 09 2012).
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 16, 2–16
Copyright of Colorectal Disease is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
M. S. Sajid et al.
Commentary on Sajid et al. Bowel cancer screening provides an opportunity to re-evaluate the therapeutic strategy for rectal cancer. In recent years there has been a rapid reduction in rectal cancer disease-associated mortality, but treatmentrelated morbidity and mortality remain high [1,2]. Long-term bowel, bladder and sexual dysfunctions are frequent complications of radical surgery for rectal cancer [3,4]. Permanent stomas are required in perhaps one-fifth of cases. The 30-day mortality for all rectal cancer surgery performed within the UK National Health Service (NHS) is 4.6% [5]. Screening using the faecal occult blood test (FOBT) identifies a high proportion of cases of rectal cancer at an early stage. In 2009, approximately 25% of the UK’s 13 970 newly diagnosed rectal tumours were Dukes A (T1/2N0). Incorporation of flexible sigmoidoscopy, a more sensitive tool than FOBT, into the national screening programme from 2014 will further promote early diagnosis [6]. Although Dukes A tumours are generally small and localized, standard treatment dictates removal of the entire organ by radical surgery. Radical surgery achieves complete rectal and mesorectal excision, providing definitive information about the T stage and local nodal metastasis. If no involved nodes are found then there is little risk of regional recurrence and a diminished risk of systemic relapse. There is no lymph node involvement (N0) in 80–85% of T1 and T2 rectal cancers [7]. Hence, routine lymph node dissection in these patients is over-treatment and could potentially be avoided. In the present issue of Colorectal Disease, Sajid et al. [8] have examined this contentious area. They performed a meta-analysis of 942 cases from 10 studies, comparing conventional treatment of pT1 and pT2 rectal cancer by radical surgery with an organpreserving approach using either transanal endoscopic microsurgery (TEMS) or chemoradiation followed by TEMS. Five papers contained a randomized comparison and the other five employed retrospective case controls. The authors acknowledge that the quality of all studies was only moderate to low at best. Heterogeneous case selection through diverse entry criteria was a particularly prominent issue. Historically, organpreserving techniques were utilized in patients who displayed signs of increased frailty and comorbidity relative to the general population. Cultural attitudes to stomas are also known to produce regional variation in practice. Two primary outcome measures were considered: overall survival and local recurrence. The authors concluded that there was no difference in distant recurrence
doi:10.1111/codi.12494
and overall survival between the two treatments, but the risk of local recurrence was higher following TEMS (OR = 2.78; 95% CI: 1.42–5.44). These results are perhaps in keeping with our preconceptions. Transanal endoscopic microsurgery alone is unlikely to be oncologically superior to radical surgery for the treatment of low rectal cancer. In particular, one would not expect stand-alone TEMS to be effective in patients with occult N+ disease. The precise proportion of N+ cases is difficult to judge, especially in our screendetected population. We would expect the overall rate to be low, and preoperative evaluation of suitability for TEMS, using endoscopy, biopsy, high-quality MRI and endorectal ultrasound (ERUS) will further bias against N+ disease. Nevertheless, some cases will evade detection, confounding subsequent comparison of the outcome of TEMS (T1-2 Nx) and radical surgery (T1-2N0), otherwise known as the Will Rogers effect. Occult nodal disease is not the only potential cause of recurrence following TEMS. We should also consider the possibility that tumour cells may be shed from the TEMS specimen and implant within the surgical wound. Mechanical washouts may reduce this risk, although their efficacy is unproven. Differentiating luminal from nodal recurrence may give a clue to the dominant mechanism of treatment failure to inform refinement of organ-preserving techniques particularly with regard to the use of contact radiotherapy. Following TEMS, a strategy of regular surveillance with MRI and endoscopy aims to identify local treatment failure in time for salvage surgery to be successful. This stepwise escalation of treatment is an attractive concept as only those patients with recurrent, aggressive disease will have the organ excised. Historical cohort studies have cast doubt upon the efficacy of salvage, but they did not benefit from modern imaging technology [9]. In addition, the motivation to detect recurrence in elderly patients is sometimes reduced. Hypothetically, if organ preservation was associated with 10–15% local failure, approximating to a hazard ratio of 2.78 compared with radical surgery, and salvage rescued just 50%, the pathway would have failed to provide local disease control in 5.0–7.5% of cases. Meanwhile, the majority of patients would retain their rectum and avoid the 4.6% risk of perioperative mortality associated with radical surgery. At the opposite end of the disease spectrum, 12% of Dukes A cancers relapse systemically following radical surgery. As the metastatic event is likely to predate surgical treatment, and the method of resection is unlikely to alter outcome, radical surgery would not be optimal care.
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 16, 2–16
15
TEMS vs RR for lower rectal cancer
M. S. Sajid et al.
The future success of organ preservation hinges upon developing treatment pathways that can deliver low failure rates, combined with early detection and treatment of local failure. Cohort studies suggest that TEMS alone results in uncomfortably high rates of local failure across the spectrum of all T1 and T2 tumours [10]. This meta-analysis included a mixture of studies: some used TEMS alone and others employed neoadjuvant chemoradiation before TEMS to improve local control. Molecular stratification of early rectal cancer using pretreatment biopsies may help to discriminate high- and low-risk cases, thus enabling more objective deployment of radiotherapy [11]. Meanwhile the Cancer Research UK (CRUK) Transanal endoscopic microsurgery and Radiotherapy for Early rectal Cancer (TREC) study is currently randomizing patients with biopsy-proven, mriT1–2 rectal cancer of less than 3 cm in diameter to have conventional radical surgery or an organ-preserving protocol of short-course preoperative radiotherapy (5x5Gy) followed by TEMS 8–10 weeks later [12]. Radiotherapy aims to resolve occult N+ mesorectal disease and reduce shedding of tumour cells at the time of TEMS surgery. Data from such high-quality randomized controlled trials are needed if we are to be able to inform patients more precisely of the best treatment for early-stage rectal cancer. Although this is a challenging process, the goal of changing the management of rectal cancer makes it an exciting and worthwhile project.
S. P. Bach*† *University of Birmingham and †Queen Elizabeth Hospital Birmingham, Birmingham, UK E-mail: [email protected]
References 1 Tekkis PP, Poloniecki JD, Thompson MR, Stamatakis JD. Operative mortality in colorectal cancer: prospective national study. BMJ 2003; 327: 1196–201.
16
2 Rutten HJ, den Dulk M, Lemmens VE, van de Velde CJ, Marijnen CA. Controversies of total mesorectal excision for rectal cancer in elderly patients. Lancet Oncol 2008; 9: 494–501. 3 Bryant CL, Lunniss PJ, Knowles CH, Thaha MA, Chan CL. Anterior resection syndrome. Lancet Oncol 2012; 13: e403–8. 4 Wallner C, Lange MM, Bonsing BA et al. Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the cooperative clinical investigators of the dutch total mesorectal excision trial. J Clin Oncol 2008; 26: 4466–72. 5 Morris EJ, Taylor EF, Thomas JD et al. Thirty-day postoperative mortality after colorectal cancer surgery in England. Gut 2011; 60: 806–13. 6 Atkin WS, Edwards R, Kralj-Hans I et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. The Lancet 2010; 375: 1624–33. 7 Chang HC, Huang SC, Chen JS et al. Risk factors for lymph node metastasis in pT1 and pT2 rectal cancer: a single-institute experience in 943 patients and literature review. Ann Surg Oncol 2012; 19: 2477–84. 8 Sajid MS, Farag S, Leung P, Sains P, Miles WFA, Baig MK. Systematic review and meta-analysis of published trials comparing the effectiveness of transanal endoscopic microsurgery (TEMS) and radical resection in the management of early rectal cancers. Colorectal Dis 2013; 16: 2–14. 9 Weiser MR, Landmann RG, Wong WD et al. Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum 2005; 48: 1169–75. 10 Bach SP, Hill J, Monson JR et al. A predictive model for local recurrence after transanal endoscopic microsurgery for rectal cancer. Br J Surg 2009; 96: 280–90. 11 Leong KJ, Wei W, Tannahill LA et al. Methylation profiling of rectal cancer identifies novel markers of early-stage disease. Br J Surg. [Research Support, Non-U.S. Gov’t]. 2011; 98: 724–34. 12 TREC study. http://www.controlled-trials.com/isrctn144 22743 (accessed 25 09 2012).
Colorectal Disease ª 2013 The Association of Coloproctology of Great Britain and Ireland. 16, 2–16
Copyright of Colorectal Disease is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
