NEWS & VIEWS Green light given for laparoscopic surgery for rectal cancer Steven D. Wexner
NPG
SURGERY
LAPAROSCOPIC RECTAL CANCER RESECTION
Refers to Bonjer, H. J. et al. A randomized trial of laparoscopic versus open surgery for rectal cancer. N. Engl. J. Med. 372, 1324–1332 (2015)
Randomized trial data support the use of laparoscopic surgery for colon cancer; however, such evidence was lacking for rectal cancer. Now, the COLOR II randomized trial gives minimally invasive resection of rectal cancer the ‘green light’, answering the question ‘should laparoscopic surgery be used?’ The new key question is ‘who should be performing laparoscopic surgery for rectal cancer?’ Soon after the description of laparoscopic colorectal surgery in 1991, an early ‘green light’ was given for the use of laparoscopy for the treatment of benign disease, but only an ‘amber light’ for resection of cancer. Thus, patients with benign diseases were able to derive the benefits of laparoscopy, such as quicker return of bowel function, decreased requirement for analgesics, shorter hospital stay, and better cosmetic results, whereas patients with malignancy were often denied these advantages. In 2002, Antonio Lacy and co-workers1 published the first randomized controlled trial demonstrating equivalence between laparo scopy and laparotomy for the treatment of colon carcinoma. The subsequent CLASICC trial2 confirmed the findings of Lacy et al.1 of equivalence for the laparoscopic and open surgical approaches for patients with colon cancer; the COLOR trial3 and COST trial 4 verified this conclusion. Thus, the light for the laparoscopic treatment of colon cancer turned from ‘amber’ to ‘green’—the last frontier for laparoscopic treatment of colorectal disease was rectal cancer. Now, the results of the COLOR II randomized trial by Bonjer et al. 5 support the use of minimally invasive laparoscopic surgery for the treatment of rectal cancer. Since the paradigm-shifting work of Richard J. ‘Bill’ Heald and others during the early-to-mid‑1980s, total mesorectal excision (TME) has become the ubiquitous worldwide standard for the safe curative surgical management of rectal carcinoma. Countless studies have shown that the
completeness of TME, the absence of involvement of the circumferential resection margins, and adequate lymph-gland harvesting, as well as appropriate, MRIguided, use of neoadjuvant therapy are critical for improving outcomes of patients with colorectal cancer. However, studies that enable determination of whether or not the laparoscopic approach is equivalent to laparotomy when applying these fundamental critical surgical tenets to the curative treatment of rectal cancer have been limited to date. With this in mind, Bonjer and colleagues5 are to be congratulated for having skilfully undertaken, masterfully executed, and authoritatively written the definitive randomized trial of laparoscopic versus open surgery for rectal cancer.
‘‘
…the last frontier for laparoscopic treatment of colorectal disease was rectal cancer
’’
In this trial, the results of which have been eagerly awaited for many years, the researchers used a 2:1 randomization schema, such that 699 patients underwent laparoscopic surgery and 345 patients received open surgery for cancers within the rectum, and achieved equivalence between the groups relative to patient demographics, and tumour location and characteristics.5 Immediate postoperative histopathological surrogate markers
NATURE REVIEWS | CLINICAL ONCOLOGY
(macroscopic completeness of the mesorectum, involved circumferential resection margins [CRM], and distal resection margins), 3‑year local recurrence rates (5% for both surgical approaches), and overall survival (86.7% for laparoscopy versus 83.6% for open surgery) were not statistically significantly different between the two groups.5 Furthermore, in the laparoscopic and open groups, the respective rates of complete TME were 84% and 88%, and the median number of lymph-nodes harvested was 13 and 14, respectively.5 Anot he r i nte re st i ng f a c e t of t he COLOR II trial was the use of a 2‑mm radial resection margin,5 rather than the 1‑mm margin as used in the COREAN random ized study of open versus laparoscopic surgery for mid-or-low rectal cancer. 6 Adherence to the requirement for 2‑mm margins might have helped to decrease the rates of not only CRM positivity, but also locoregional recurrence at 3 years. It was also very encouraging that laparo scopy was associated with superior CRMs as compared with laparotomy in patients with distal lesions (involved CRM rates of 9% versus 22%).5 Furthermore, although 3‑year disease-free survival (DFS) rates were similar between the groups for patients with stage I or stage II disease, Bonjer et al.5 reported DFS rates of 64.9% and 52% in patients with stage III rectal cancer who underwent laparoscopy and laparotomy, respectively. This survival advantage in favour of laparoscopy is in keeping with the prior findings of Lacy et al.1 for patients with stage III colon cancer. These consistent DFS advantages in patients with stage III colorectal cancer might be, at least in part, due to substantially reduced immune suppression when the resections are performed laparoscopically.7 VOLUME 12 | JULY 2015
© 2015 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS
‘‘
…the results … support the use of minimally invasive laparoscopic surgery for the treatment of rectal cancer
’’
In light of these findings, Bonjer and co-workers are to be commended for demonstrating the safe, oncologically appropriate application of the laparoscope for the curative treatment of patients with rectal carcinoma. Now that this green light has clearly been activated for us, we need to be cognizant of who should perform laparoscopic rectal cancer surgery, and must at all times be honest with our patients. The learning curve for laparoscopic colorectal surgery overall has been estimated as anywhere between a minimum of 20–120 surgeries.8,9 Therefore, the individual surgeon must be mindful of his or her annual rectal cancer volumes when making the decision about which technique to use. Although the COLOR II expert team of investigators at 30 hospitals in eight countries has proven that these laudable results are possible, the surgeon who performs only one rectal cancer resection every few weeks might not be able to master the laparoscopic TME learning curve sufficiently to confer these same benefits on their patients. Therefore, the current question is no longer ‘is laparo scopy equivalent to laparotomy for the curative treatment of rectal cancer?’, but rather ‘who should be performing laparoscopic rectal cancer resections?’ Once again, our colleagues in Europe have deftly demonstrated that centralization of rectal cancer care and the mandatory participation in centres of excellence
JULY 2015 | VOLUME 12
can significantly improve patient outcomes, including reduced rates of local recurrence, reduced incidence of permanent stoma formation, and reduced morbid ity. 5 Fortunately, the American College of Surgeons and the Commission on Cancer (CoC) have recently endorsed and adopted the programme proposed by the Consortium for Optimizing the Surgical Treatment of Rectal Cancer (OSTRiCh).10 This programme has been created not to exclude surgeons from performing rectal cancer surgery, but rather to allow patients access to surgeons performing these procedures at CoC-accredited facilities with additional accreditation for rectal cancer management. I would like to conclude by again congratulating Bonjer and colleagues for having turned our global light for the performance of curative laparoscopic TME of colorectal cancers from amber to green. We must now determine how best to develop and deliver this surgical modality at centres in different health-care systems worldwide to maximize the benefits for patients with rectal cancer. Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA. [email protected] doi:10.1038/nrclinonc.2015.100 Published online 26 May 2015 Acknowledgements The author would like to acknowledge Dr Nadav Haim and Dr Isacco Montroni for their assistance with the preparation of this article for publication. Competing interests S.D.W. declares potential royalties for inventor’s income from Covidien and Karl Storz. S.D.W. has also acted as a consultant for and received consulting fees from Karl Storz.
1.
Lacy, A. M. et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359, 2224–2229 (2002). 2. Guillou, P. J. et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicenter, randomised controlled trial. Lancet 365, 1718–1726 (2005). 3. Veldkamp, R. et al. Laparoscopic surgery versus open surgery for colon cancer: shortterm outcomes of a randomised trial. Lancet Oncol. 6, 477–484 (2005). 4. Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N. Engl. J. Med. 350, 2050–2059 (2004). 5. Bonjer, H. J. et al. A randomized trial of laparoscopic versus open surgery for rectal cancer. N. Engl. J. Med. 372, 1324–1332 (2015). 6. Kang, S. B. et al. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short term outcomes of an open-label randomized controlled trial. Lancet Oncol. 11, 637–645 (2010). 7. Veenhof, A. A. et al. The surgical stress response and postoperative immune function after laparoscopic or conventional total mesorectal excision in rectal cancer: a randomized trial. Int. J. Colorectal Dis. 26, 53–59 (2011). 8. Tekkis, P. P., Senagore, A. J., Delaney, C. P. & Fazio, V. W. Evaluation of the learning curve in laparoscopic colorectal surgery: comparison of right-sided and left-sided resections. Ann. Surg. 242, 83–91 (2005). 9. Miskovic, D., Ni, M., Wyles, S. M., Tekkis, P. & Hanna, G. B. Learning curve and case selection in laparoscopic colorectal surgery: systematic review and international multicenter analysis of 4852 cases. Dis. Colon Rectum 55, 1300–1310 (2012). 10. Dietz, D. W. Consortium for optimizing surgical treatment of rectal cancer (OSTRiCh). Multidisciplinary management of rectal cancer: the OSTRiCh. J. Gastrointest. Surg. 17, 1863–1868 (2013).
www.nature.com/nrclinonc © 2015 Macmillan Publishers Limited. All rights reserved
NPG
SURGERY
LAPAROSCOPIC RECTAL CANCER RESECTION
Refers to Bonjer, H. J. et al. A randomized trial of laparoscopic versus open surgery for rectal cancer. N. Engl. J. Med. 372, 1324–1332 (2015)
Randomized trial data support the use of laparoscopic surgery for colon cancer; however, such evidence was lacking for rectal cancer. Now, the COLOR II randomized trial gives minimally invasive resection of rectal cancer the ‘green light’, answering the question ‘should laparoscopic surgery be used?’ The new key question is ‘who should be performing laparoscopic surgery for rectal cancer?’ Soon after the description of laparoscopic colorectal surgery in 1991, an early ‘green light’ was given for the use of laparoscopy for the treatment of benign disease, but only an ‘amber light’ for resection of cancer. Thus, patients with benign diseases were able to derive the benefits of laparoscopy, such as quicker return of bowel function, decreased requirement for analgesics, shorter hospital stay, and better cosmetic results, whereas patients with malignancy were often denied these advantages. In 2002, Antonio Lacy and co-workers1 published the first randomized controlled trial demonstrating equivalence between laparo scopy and laparotomy for the treatment of colon carcinoma. The subsequent CLASICC trial2 confirmed the findings of Lacy et al.1 of equivalence for the laparoscopic and open surgical approaches for patients with colon cancer; the COLOR trial3 and COST trial 4 verified this conclusion. Thus, the light for the laparoscopic treatment of colon cancer turned from ‘amber’ to ‘green’—the last frontier for laparoscopic treatment of colorectal disease was rectal cancer. Now, the results of the COLOR II randomized trial by Bonjer et al. 5 support the use of minimally invasive laparoscopic surgery for the treatment of rectal cancer. Since the paradigm-shifting work of Richard J. ‘Bill’ Heald and others during the early-to-mid‑1980s, total mesorectal excision (TME) has become the ubiquitous worldwide standard for the safe curative surgical management of rectal carcinoma. Countless studies have shown that the
completeness of TME, the absence of involvement of the circumferential resection margins, and adequate lymph-gland harvesting, as well as appropriate, MRIguided, use of neoadjuvant therapy are critical for improving outcomes of patients with colorectal cancer. However, studies that enable determination of whether or not the laparoscopic approach is equivalent to laparotomy when applying these fundamental critical surgical tenets to the curative treatment of rectal cancer have been limited to date. With this in mind, Bonjer and colleagues5 are to be congratulated for having skilfully undertaken, masterfully executed, and authoritatively written the definitive randomized trial of laparoscopic versus open surgery for rectal cancer.
‘‘
…the last frontier for laparoscopic treatment of colorectal disease was rectal cancer
’’
In this trial, the results of which have been eagerly awaited for many years, the researchers used a 2:1 randomization schema, such that 699 patients underwent laparoscopic surgery and 345 patients received open surgery for cancers within the rectum, and achieved equivalence between the groups relative to patient demographics, and tumour location and characteristics.5 Immediate postoperative histopathological surrogate markers
NATURE REVIEWS | CLINICAL ONCOLOGY
(macroscopic completeness of the mesorectum, involved circumferential resection margins [CRM], and distal resection margins), 3‑year local recurrence rates (5% for both surgical approaches), and overall survival (86.7% for laparoscopy versus 83.6% for open surgery) were not statistically significantly different between the two groups.5 Furthermore, in the laparoscopic and open groups, the respective rates of complete TME were 84% and 88%, and the median number of lymph-nodes harvested was 13 and 14, respectively.5 Anot he r i nte re st i ng f a c e t of t he COLOR II trial was the use of a 2‑mm radial resection margin,5 rather than the 1‑mm margin as used in the COREAN random ized study of open versus laparoscopic surgery for mid-or-low rectal cancer. 6 Adherence to the requirement for 2‑mm margins might have helped to decrease the rates of not only CRM positivity, but also locoregional recurrence at 3 years. It was also very encouraging that laparo scopy was associated with superior CRMs as compared with laparotomy in patients with distal lesions (involved CRM rates of 9% versus 22%).5 Furthermore, although 3‑year disease-free survival (DFS) rates were similar between the groups for patients with stage I or stage II disease, Bonjer et al.5 reported DFS rates of 64.9% and 52% in patients with stage III rectal cancer who underwent laparoscopy and laparotomy, respectively. This survival advantage in favour of laparoscopy is in keeping with the prior findings of Lacy et al.1 for patients with stage III colon cancer. These consistent DFS advantages in patients with stage III colorectal cancer might be, at least in part, due to substantially reduced immune suppression when the resections are performed laparoscopically.7 VOLUME 12 | JULY 2015
© 2015 Macmillan Publishers Limited. All rights reserved
NEWS & VIEWS
‘‘
…the results … support the use of minimally invasive laparoscopic surgery for the treatment of rectal cancer
’’
In light of these findings, Bonjer and co-workers are to be commended for demonstrating the safe, oncologically appropriate application of the laparoscope for the curative treatment of patients with rectal carcinoma. Now that this green light has clearly been activated for us, we need to be cognizant of who should perform laparoscopic rectal cancer surgery, and must at all times be honest with our patients. The learning curve for laparoscopic colorectal surgery overall has been estimated as anywhere between a minimum of 20–120 surgeries.8,9 Therefore, the individual surgeon must be mindful of his or her annual rectal cancer volumes when making the decision about which technique to use. Although the COLOR II expert team of investigators at 30 hospitals in eight countries has proven that these laudable results are possible, the surgeon who performs only one rectal cancer resection every few weeks might not be able to master the laparoscopic TME learning curve sufficiently to confer these same benefits on their patients. Therefore, the current question is no longer ‘is laparo scopy equivalent to laparotomy for the curative treatment of rectal cancer?’, but rather ‘who should be performing laparoscopic rectal cancer resections?’ Once again, our colleagues in Europe have deftly demonstrated that centralization of rectal cancer care and the mandatory participation in centres of excellence
JULY 2015 | VOLUME 12
can significantly improve patient outcomes, including reduced rates of local recurrence, reduced incidence of permanent stoma formation, and reduced morbid ity. 5 Fortunately, the American College of Surgeons and the Commission on Cancer (CoC) have recently endorsed and adopted the programme proposed by the Consortium for Optimizing the Surgical Treatment of Rectal Cancer (OSTRiCh).10 This programme has been created not to exclude surgeons from performing rectal cancer surgery, but rather to allow patients access to surgeons performing these procedures at CoC-accredited facilities with additional accreditation for rectal cancer management. I would like to conclude by again congratulating Bonjer and colleagues for having turned our global light for the performance of curative laparoscopic TME of colorectal cancers from amber to green. We must now determine how best to develop and deliver this surgical modality at centres in different health-care systems worldwide to maximize the benefits for patients with rectal cancer. Department of Colorectal Surgery, Cleveland Clinic Florida, 2950 Cleveland Clinic Boulevard, Weston, FL 33331, USA. [email protected] doi:10.1038/nrclinonc.2015.100 Published online 26 May 2015 Acknowledgements The author would like to acknowledge Dr Nadav Haim and Dr Isacco Montroni for their assistance with the preparation of this article for publication. Competing interests S.D.W. declares potential royalties for inventor’s income from Covidien and Karl Storz. S.D.W. has also acted as a consultant for and received consulting fees from Karl Storz.
1.
Lacy, A. M. et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 359, 2224–2229 (2002). 2. Guillou, P. J. et al. Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicenter, randomised controlled trial. Lancet 365, 1718–1726 (2005). 3. Veldkamp, R. et al. Laparoscopic surgery versus open surgery for colon cancer: shortterm outcomes of a randomised trial. Lancet Oncol. 6, 477–484 (2005). 4. Clinical Outcomes of Surgical Therapy Study Group. A comparison of laparoscopically assisted and open colectomy for colon cancer. N. Engl. J. Med. 350, 2050–2059 (2004). 5. Bonjer, H. J. et al. A randomized trial of laparoscopic versus open surgery for rectal cancer. N. Engl. J. Med. 372, 1324–1332 (2015). 6. Kang, S. B. et al. Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short term outcomes of an open-label randomized controlled trial. Lancet Oncol. 11, 637–645 (2010). 7. Veenhof, A. A. et al. The surgical stress response and postoperative immune function after laparoscopic or conventional total mesorectal excision in rectal cancer: a randomized trial. Int. J. Colorectal Dis. 26, 53–59 (2011). 8. Tekkis, P. P., Senagore, A. J., Delaney, C. P. & Fazio, V. W. Evaluation of the learning curve in laparoscopic colorectal surgery: comparison of right-sided and left-sided resections. Ann. Surg. 242, 83–91 (2005). 9. Miskovic, D., Ni, M., Wyles, S. M., Tekkis, P. & Hanna, G. B. Learning curve and case selection in laparoscopic colorectal surgery: systematic review and international multicenter analysis of 4852 cases. Dis. Colon Rectum 55, 1300–1310 (2012). 10. Dietz, D. W. Consortium for optimizing surgical treatment of rectal cancer (OSTRiCh). Multidisciplinary management of rectal cancer: the OSTRiCh. J. Gastrointest. Surg. 17, 1863–1868 (2013).
www.nature.com/nrclinonc © 2015 Macmillan Publishers Limited. All rights reserved
