PERSPECTIVES ANZJSurg.com
Complete clinical response to neoadjuvant chemoradiotherapy for rectal cancer: an Australasian perspective Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the accepted standard of care for locally advanced rectal cancer in Australasia.1 nCRT is associated with a pathological complete response (PCR) in approximately 20% of patients. At present, the optimal treatment strategy following nCRT is surgical resection for all patients irrespective of response to nCRT. However, surgery exposes patients to specific risks, including a significant risk of mortality, anastomotic leak, morbidity, the potential for a permanent stoma and impairment of bowel, bladder and sexual function. In patients with PCR, these risks may be taken without additional benefit in terms of local recurrence or disease-free survival.2,3 Patients with PCR are known to have similar oncological outcomes to stage 1 disease and combining this superior prognosis with avoiding unnecessary and potentially mutilating surgery provides a tantalizing management protocol. One difficulty is accurately defining preoperatively which patients have achieved a complete pathological response without a histological specimen; currently, the degree of clinical response has been utilized by some groups to estimate PCR and avoid surgery.2 While this has not been accepted as routine practice, it is an area that continues to provide controversy and debate among surgeons and oncologists. The perspective of the members of the Colorectal Surgical Society of Australia and New Zealand (ANZ) on the management of complete clinical response (CCR) following nCRT was assessed by a questionnaire in 2011. This questionnaire was modelled on and compared with a study in the United Kingdom (UK) conducted by Wynn et al.4 Sixty-six surgeons responded to the questionnaire out of 154 surgeons contacted, providing a response rate of 43%. The respondents represented an experienced group of specialist colorectal surgeons, with 36 (54.6%) of respondents having greater than 10 years experience as a specialist surgeon. This survey demonstrated that the opinion of Australian and New Zealand colorectal surgeons with respect to the management of CCR following nCRT remains divided. While 50% of surgeons would consider a watch and wait policy in those patients with no clinical evidence of residual disease, only 33.3% report discussing this with a patient who is fit for operative management. Over 70% of surgeons stated they would not change their decision to perform an abdomino-perineal resection (APR) in a patient with CCR. However, when provided with clinical vignette describing a patient with a tumour at 4 cm and a CCR, 54.5% felt that a CCR would allow for sphincter-sparing surgery and avoid an APR. There is currently no standardized algorithm to assess and define CCR that is widely accepted. When asked what methods were preferred to assess CCR, the response varied among surgeons, with the © 2015 Royal Australasian College of Surgeons
majority of surgeons utilizing multiple complementary methods of assessment highlighting the lack of consensus in what defines CCR and also the poor reliability of a single assessment technique. The prescribed management of patients with rectal cancer is similar in the UK and Australia. In keeping with this, the majority of answers from ANZ surgeons were consistent with UK surgeons. However, UK surgeons were more willing to accept that a CCR would allow for sphincter-preserving surgery in a patient with a low rectal cancer than ANZ surgeons. Almost half of ANZ surgeons would recommend a permanent stoma compared with one-third of UK surgeons. It would appear that while surgeons feel that a good response to nCRT allows for less radical surgery, however, they are not willing to extrapolate this reasoning into non-operative management. Surgeons in both countries were more willing to consider a non-operative approach in a patient with greater co-morbidities than in a patient who was fit for surgery. The lack of reliable pathological criteria for PCR is potentially one of the reasons surgeons lack confidence in a conservative approach to a CCR. When provided with the pathology report of a resected specimen demonstrating a CPR, a low percentage of surgeons in both the UK (14%) and ANZ (16.7%) were willing to interpret this as being equivalent to no residual tumour cells in the specimen. This possibly reflects surgeons concerns regarding sampling error in pathology specimens. This is perhaps reflected in the fact that while over 50% of surgeons are intellectually willing to consider non-operative management, a much smaller number are willing to discuss this approach with their patients. Australian and New Zealand surgeons, similar to their UK colleagues, express a willingness to manage patients with complete clinical response to neoadjuvant therapy conservatively; however, the clinical application of this approach remains limited due to the lack of robust clinical evidence, reliable assessment methods and the availability of clinical trials. Research shows promise in the use of magnetic resonance imaging and 18-fluorodeoxyglucose positron emission tomography/computed tomography to define CCR preoperatively; however, neither of these methods demonstrate adequate specificity and sensitivity to guide surgical management.5 Greater information from randomized controlled trials and reliable molecular and radiological markers of CCR are needed before there is wider acceptance of a ‘watch and wait’ policy among clinicians. References 1. Committee ACNCCGR. Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer. Sydney: The Cancer Council Australia and Australian Cancer Network; 2005.
ANZ J Surg 85 (2015) 103–104
104
2. Habr-Gama A, Perez RO. Non-operative management of rectal cancer after neoadjuvant chemoradiation. Br. J. Surg. 2009; 96: 125–7. 3. Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br. J. Surg. 2012; 99: 897–909. 4. Wynn GR, Bhasin N, Macklin CP, George ML. Complete clinical response to neoadjuvant chemoradiotherapy in patients with rectal cancer: opinions of British and Irish specialists. Colorectal Dis. 2010; 12: 327– 33. 5. Fischkoff KN, Ruby JA, Guillem JG. Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective. Clin. Colorectal Cancer 2011; 10: 291–7.
Perspectives
Cori Behrenbruch,* BPharm, MMBS Jennifer Ryan,*† BSc, MBBS, FRACS Craig Lynch,* MBChB, MMedSci, FCSSANZ, FASCRS (Int), FRACS Gregory Wynn,§ BSc, MD, FRCS Alexander Heriot,* MA, MD, MBA, FRACS, FRCS (Gen) *Department of Cancer Surgery, Peter MacCallum Cancer Centre, †General Surgery Clinical Institute, Epworth Healthcare, Melbourne, Victoria, Australia and §Department of General Surgery, ICENI Centre, Colchester, UK doi: 10.1111/ans.12441
© 2015 Royal Australasian College of Surgeons
Complete clinical response to neoadjuvant chemoradiotherapy for rectal cancer: an Australasian perspective Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision and adjuvant chemotherapy is the accepted standard of care for locally advanced rectal cancer in Australasia.1 nCRT is associated with a pathological complete response (PCR) in approximately 20% of patients. At present, the optimal treatment strategy following nCRT is surgical resection for all patients irrespective of response to nCRT. However, surgery exposes patients to specific risks, including a significant risk of mortality, anastomotic leak, morbidity, the potential for a permanent stoma and impairment of bowel, bladder and sexual function. In patients with PCR, these risks may be taken without additional benefit in terms of local recurrence or disease-free survival.2,3 Patients with PCR are known to have similar oncological outcomes to stage 1 disease and combining this superior prognosis with avoiding unnecessary and potentially mutilating surgery provides a tantalizing management protocol. One difficulty is accurately defining preoperatively which patients have achieved a complete pathological response without a histological specimen; currently, the degree of clinical response has been utilized by some groups to estimate PCR and avoid surgery.2 While this has not been accepted as routine practice, it is an area that continues to provide controversy and debate among surgeons and oncologists. The perspective of the members of the Colorectal Surgical Society of Australia and New Zealand (ANZ) on the management of complete clinical response (CCR) following nCRT was assessed by a questionnaire in 2011. This questionnaire was modelled on and compared with a study in the United Kingdom (UK) conducted by Wynn et al.4 Sixty-six surgeons responded to the questionnaire out of 154 surgeons contacted, providing a response rate of 43%. The respondents represented an experienced group of specialist colorectal surgeons, with 36 (54.6%) of respondents having greater than 10 years experience as a specialist surgeon. This survey demonstrated that the opinion of Australian and New Zealand colorectal surgeons with respect to the management of CCR following nCRT remains divided. While 50% of surgeons would consider a watch and wait policy in those patients with no clinical evidence of residual disease, only 33.3% report discussing this with a patient who is fit for operative management. Over 70% of surgeons stated they would not change their decision to perform an abdomino-perineal resection (APR) in a patient with CCR. However, when provided with clinical vignette describing a patient with a tumour at 4 cm and a CCR, 54.5% felt that a CCR would allow for sphincter-sparing surgery and avoid an APR. There is currently no standardized algorithm to assess and define CCR that is widely accepted. When asked what methods were preferred to assess CCR, the response varied among surgeons, with the © 2015 Royal Australasian College of Surgeons
majority of surgeons utilizing multiple complementary methods of assessment highlighting the lack of consensus in what defines CCR and also the poor reliability of a single assessment technique. The prescribed management of patients with rectal cancer is similar in the UK and Australia. In keeping with this, the majority of answers from ANZ surgeons were consistent with UK surgeons. However, UK surgeons were more willing to accept that a CCR would allow for sphincter-preserving surgery in a patient with a low rectal cancer than ANZ surgeons. Almost half of ANZ surgeons would recommend a permanent stoma compared with one-third of UK surgeons. It would appear that while surgeons feel that a good response to nCRT allows for less radical surgery, however, they are not willing to extrapolate this reasoning into non-operative management. Surgeons in both countries were more willing to consider a non-operative approach in a patient with greater co-morbidities than in a patient who was fit for surgery. The lack of reliable pathological criteria for PCR is potentially one of the reasons surgeons lack confidence in a conservative approach to a CCR. When provided with the pathology report of a resected specimen demonstrating a CPR, a low percentage of surgeons in both the UK (14%) and ANZ (16.7%) were willing to interpret this as being equivalent to no residual tumour cells in the specimen. This possibly reflects surgeons concerns regarding sampling error in pathology specimens. This is perhaps reflected in the fact that while over 50% of surgeons are intellectually willing to consider non-operative management, a much smaller number are willing to discuss this approach with their patients. Australian and New Zealand surgeons, similar to their UK colleagues, express a willingness to manage patients with complete clinical response to neoadjuvant therapy conservatively; however, the clinical application of this approach remains limited due to the lack of robust clinical evidence, reliable assessment methods and the availability of clinical trials. Research shows promise in the use of magnetic resonance imaging and 18-fluorodeoxyglucose positron emission tomography/computed tomography to define CCR preoperatively; however, neither of these methods demonstrate adequate specificity and sensitivity to guide surgical management.5 Greater information from randomized controlled trials and reliable molecular and radiological markers of CCR are needed before there is wider acceptance of a ‘watch and wait’ policy among clinicians. References 1. Committee ACNCCGR. Guidelines for the Prevention, Early Detection and Management of Colorectal Cancer. Sydney: The Cancer Council Australia and Australian Cancer Network; 2005.
ANZ J Surg 85 (2015) 103–104
104
2. Habr-Gama A, Perez RO. Non-operative management of rectal cancer after neoadjuvant chemoradiation. Br. J. Surg. 2009; 96: 125–7. 3. Glynne-Jones R, Hughes R. Critical appraisal of the ‘wait and see’ approach in rectal cancer for clinical complete responders after chemoradiation. Br. J. Surg. 2012; 99: 897–909. 4. Wynn GR, Bhasin N, Macklin CP, George ML. Complete clinical response to neoadjuvant chemoradiotherapy in patients with rectal cancer: opinions of British and Irish specialists. Colorectal Dis. 2010; 12: 327– 33. 5. Fischkoff KN, Ruby JA, Guillem JG. Nonoperative approach to locally advanced rectal cancer after neoadjuvant combined modality therapy: challenges and opportunities from a surgical perspective. Clin. Colorectal Cancer 2011; 10: 291–7.
Perspectives
Cori Behrenbruch,* BPharm, MMBS Jennifer Ryan,*† BSc, MBBS, FRACS Craig Lynch,* MBChB, MMedSci, FCSSANZ, FASCRS (Int), FRACS Gregory Wynn,§ BSc, MD, FRCS Alexander Heriot,* MA, MD, MBA, FRACS, FRCS (Gen) *Department of Cancer Surgery, Peter MacCallum Cancer Centre, †General Surgery Clinical Institute, Epworth Healthcare, Melbourne, Victoria, Australia and §Department of General Surgery, ICENI Centre, Colchester, UK doi: 10.1111/ans.12441
© 2015 Royal Australasian College of Surgeons
