Indian J Surg DOI 10.1007/s12262-014-1089-3
ORIGINAL ARTICLE
Paradigm Shift in the Management of Rectal Cancer Nihit Rawat & Martyn D. Evans
Received: 24 February 2014 / Accepted: 23 April 2014 # Association of Surgeons of India 2014
Abstract Surgery for rectal cancer in the pre-Total Mesorectal Excision (TME) era was associated with high local recurrence rates. The widespread adoption of the TME technique together with the addition of neoadjuvant oncological therapies have reduced local failure rates and improved survival for patients with rectal cancer. Advances in our knowledge, better understanding of tumour biology and refinement in minimal access techniques and equipment have significantly changed the management of rectal cancer. This paper reviews these changes and proposes a paradigm shift in how rectal cancer management is conceptualised and treated, such that the treatment of rectal cancer is separated into early tumours (potentially suitable for local excison), TME tumours (optimally managed by TME) and beyond TME tumours (optimally managed by multivisceral resection outside the TME plane). Keywords Chemoradiatherapy . Rectal cancer . Total mesorectal excision . Multivisceral resection
Introduction Worldwide, half a million patients are diagnosed with colorectal cancer each year, of which approximately one third are located in the rectum. In the last 30 years, the management of rectal cancer has been refined with improvements in surgical technique, radiological staging and use of neoadjuvant oncological treatment. A patient who presents with rectal cancer wants to be cured with as little impact on their quality of life as possible. It is N. Rawat Advanced Pelvic Oncology Fellow, Swansea Colorectal Unit, Swansea, UK M. D. Evans (*) Swansea Colorectal Unit, Colorectal Surgeon, Morriston Hospital, Heol Maes Eglwys, Morriston, Swansea SA6 6NL, UK e-mail: [email protected]
generally accepted that surgical resection with a clear circumferential margin will be required to achieve cure. Historically, surgery for rectal cancer was performed as expediently as possible by blunt blind dissection that yielded poor oncological results with high rates of local failure. In 1982, Heald reported the technique of total mesorectal excision (TME) that removed the rectal bowel tube along with the surrounding mesorectal envelope. Since, TME has been adopted worldwide as the surgical technique of choice to treat rectal cancer [1–3]. The use of TME has reduced local recurrence rates following surgery from 30 to under 10 % in large national audits [4]. Whilst surgery in the TME plane appears optimal for most rectal cancers, there is however, a problem in its use for tumours in the lower rectum at the level where the rectum goes through the pelvic floor. Tumours at this height are typically treated by abdominoperineal excision (APE). At this level, the mesorectum narrows; dissection in the TME plane therefore culminates in dissection between the levator ani muscles and the fascia propria of the rectum. This risk entering the tumour, which may lead to an involved circumferential resection margin (CRM) and greatly increases the risk of local recurrence [5]. Large national audits have demonstrated that the CRM involvement rates are far higher after APE than after anterior resection [6]. As a consequence of the high local failure rates in patients undergoing APE, the technique of extralevator abdominoperineal excision (ELAPE) has been promulgated by Holm. ELAPE involves wide excision of the pelvic floor en bloc with the rectum mobilised in the TME plane to the top of the pelvic floor [7]. Adoption of the ELAPE technique has been shown to reduce local recurrence rates after APE [8]. Whilst refinement of surgical techniques have improved outcomes from tumours treated by TME or ELAPE surgery, there are other developments that have also improved outcomes and surgical planning for tumours excised in the TME/ELAPE plane including: improved radiological staging, the use of neoadjuvant therapy and improvements in minimally invasive equipment and skills.
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Aside from TME/ELAPE surgery, our improved understanding of the pathology of early rectal cancer has led to increased use of local excision as a definitive treatment [9]. At the other end of the pathological spectrum, there has been a recent focus on the management of locally advanced rectal cancer (LARC) and performing surgical resection beyond the TME plane [10]. This paper reviews the developments in rectal cancer management over recent years and proposes a change in thinking about how rectal cancer management is conceptualised and treated.
Definition of the Rectum What constitutes the “rectum” is a contentious issue with differing surgical, radiological and anatomical definitions described. Anatomically, the rectum is 12–15 cm long and starts at the level of the S3 sacral vertebra and ends at the level of the anal canal [11]. Radiologically, judged on magnetic resonance imaging (MRI) criteria, the rectum is the portion of the large bowel below the level of the sacral promontory with a clearly definable mesorectum posteriorly [10]. From a surgical perspective, the rectum starts at the point of fusion of the two antemesenteric taenias on the sigmoid colon; this usually corresponds to the level of the sacral promontory. Whilst there are different definitions, it is important to have a clear definition of what constitutes a rectum because the treatment of rectal cancer differs from that of colonic cancer in some important areas, particularly in the use of peri-operative radiotherapy [12]. Consequently, in 1999, representatives of the American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland and Australian Societies met to agree on a definition of the rectal cancer. This resulted in rectal cancer being defined as any tumour whose distal margin is visible at or below 15 cm from the anal verge on rigid sigmoidoscopy [10, 12].
Preoperative Imaging All patients with rectal cancer should have staging investigations to assess the presence of synchronous tumours, local invasion, nodal disease and distant metastases. Therefore, all patients should have a complete large bowel evaluation; computed tomography (CT) scan of the chest, abdomen and pelvis to search for metastatic disease and MRI scan of the pelvis to locally stage the tumour and assess nodal and contiguous organ involvement. In some centres, endorectal ultrasonography (ERUS) is used as an alternative or in addition to MRI for local staging and may be particularly useful in the assessment of patients with mid and low early rectal cancer.
Computed Tomography (CT) All patients with rectal cancer should have a CT scan of the chest, abdomen and pelvis to assess local and distal spread of the disease [12, 13]. However, the role of CT in local staging of the primary tumour is limited by poor sensitivity and specificity for T stage and N stage when compared to ERUS and MRI [14, 15]. Therefore at the present time, the main role of CT is in the assessment of distant metastases. Magnetic Resonance Imaging (MRI) All patients being considered for surgical resection of rectal cancer should undergo MRI assessment. The rational for this is that MRI can predict the T and N stage of a rectal tumour more accurately than CT and is superior at identifying contiguous organ involvement, a threatened CRM or the presence of extra-mural vascular invasion, which may influence the decision to use neoadjuvant treatment [16–18]. Endorectal Ultrasound (ERUS) ERUS offers an alternative technique to MRI to stage the primary tumour and is particularly helpful in assessment of mid and low rectal tumours. Although ERUS is operator dependent, it is considered to be more accurate than MRI in defining T stage of early tumours (benign versus T1/2) and also in the distinction between T3 tumours which may influence the decision to give preoperative neoadjuvant therapy [14]. However, ERUS is considered to be inferior to MRI in the assessment of lymph node involvement and a threatened CRM although it has similar accuracy in the assessment of contiguous organ involvement [14]. A number of studies have attempted to establish whether MRI or ERUS is the more accurate modality to locally stage rectal cancer [19–21]. However, there does not appear to be a clear answer, as both have their merits and disadvantages. The authors believe that both may individually yield useful information that if used synergistically allows for optimal decisionmaking for the patient with rectal cancer, it is therefore our practice to use both in all patients treated with rectal cancer (Fig. 1).
Management of Rectal Cancer Once a patient with rectal cancer has been staged, the patient should be discussed in a colorectal cancer multidisciplinary team (MDT) meeting [22, 23]. Whilst up to 20 % of patients have metastases at presentation, usually making cure impossible, the majority of rectal cancer patients do not have metastases at presentation and are treated with curative intent and
Indian J Surg Fig. 1 Comparative ERUS and MR in a T4 rectal cancer invading prostate. ERUS and MRI images of the same patient. MR showed possible prostatic involvement, ERUS demonstrated unequivocal prostate involvement, demonstrating the advantage of multimodal imaging
surgery with or without neoadjuvant treatments (radiotherapy (RT) and chemotherapy) remains the mainstay of treatment. The Role of Preoperative Neoadjuvant Therapy The MDT management of rectal cancer with curative intent has changed in the last two decades; neoadjuvant oncological treatment, prior to TME/ELAPE surgery, are now commonly used with the aim of improved local disease control and survival in selected patients. It is accepted that preoperative radiotherapy is more efficacious than postoperative (adjuvant) treatment at achieving local control [24, 25]. The two widely accepted approaches to preoperative treatment are either short course preoperative radiotherapy (SCPRT) or long course chemoradiotherapy (CRT). A detailed discussion of these is beyond the scope of this manuscript but broadly, SCPRT has been advocated by some for most rectal cancers. CRT is generally considered for more advanced and lower third rectal cancers to try and downstage a tumour. The rational for SCPRT for most patients are the results of three large European trials [26–28] and the UK’s CR07 trial [24] that reported improved local control and possibly improved survival for rectal cancer patients treated with SCPRT against those treated with surgery alone. However, some of these trials have been criticised for the lack of TME surgical resection in the surgery arm and the benefit observed has been labelled secondary to the effect of RT compensating for poor surgical quality. Long course neoadjuvant CRT is generally utilised for the more advanced and lower third rectal cancers. The technique was evaluated in the German rectal cancer trial [25, 29], which randomised patients between preoperative treatment with 5FU and long course radiotherapy with the same chemoradiotherapy protocol administered postoperatively for patients with locally advanced rectal cancer (LARC). The trial reported improved local control and sphincter preservation with
preoperative chemoradiotherapy. However, there was no difference in overall survival [25, 29]. At the present time, the indications for radiotherapy in rectal cancer management are not standardised. Whilst the data from the European trials supports the use of SCPRT in all operable rectal cancers, its uptake in the UK has been variable. A recent UK national audit reported that the use of SCPRT in elective rectal cancer resections varied between MDTs, with a range of 0 to 30 % of patients having elective rectal resection for cancer [30]. Advocates for SCPRT argue that it should be given to all patients due to the improved local disease control demonstrated in the European trials. Opponents to SCPRT for all patients argue that the trials were compromised by poor quality surgery. These opponents also argue that radiotherapy is not without risk and may cause worse bowel function and increased urinary and sexual dysfunction in patients treated, and these risks need to be balanced against the potential benefit in terms of local control [31, 32]. In more advanced tumours, both SCPRT and CRT have been advocated. Trials comparing the two treatments suggest that CRT may increase downsizing and downstaging when compared to SCPRT, but this has not translated into improved long-term survival [33–35]. In light of these results in patients with more locally advanced tumours, in which the benefits of tumour downsizing outweigh the potential functional risks of radiotherapy, long course treatment appears to achieve better local control than short course radiation therapy and remains the preferred choice for locally advanced rectal cancers in most centres. The Role of Complete Response to CRT in Rectal Cancer Management Most series of patients treated with CRT include some who have a complete clinical and pathological response to
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treatment [36]. At present, subsequent surgical resection remains the standard of care even if a complete response is suspected. The rational for this is concern that there may be undetected microscopic disease or that the disease will recur [37]. There has however been interest in the work of HabrGama and colleagues who have reported their experience of observation rather than resection in patients who have a complete response [38]. They have also modified the standard CRT regimens to include additional chemotherapy during the resting period following long course radiotherapy to maximise the chance of a complete response. They have reported at a median follow up of 56 months that 50 % of their patients have not required surgical resection [39]. Based on this, they advocate a selective wait and watch approach for the patients with complete clinical response to neoadjuvant chemoradiotherapy [39]. Whilst Habr-Gama and colleagues have experienced very encouraging results, other series have not shown such high complete response rates and therefore until more evidence is available caution must be adopted in the widespread adoption of this technique [40–42].
Fig. 2 Specimen images of TEMS, total mesorectal excision and multivisceral resection
(potentially suitable for local excision), TME tumours (optimally managed by TME) and beyond TME tumours (optimally managed by multivisceral resection outside the TME plane) (Fig. 2).
Surgery for Rectal Cancer
Management of Early Rectal Cancer and the Malignant Polyp
Surgery with or without prior neoadjuvant therapy remains the mainstay of treatment of rectal cancer with curative intent. The goal of surgery in this setting is complete excision of the tumour, with a clear circumferential margin (R0). If this is achieved, the risk of local recurrence is minimised [43]. Whilst TME/ELAPE surgery is now an accepted standard of care in rectal cancer surgery, how this is performed has evolved with advances in laparoscopic and robotic equipment and expertise. Whether all patients with rectal cancer should be treated by TME/ELAPE surgery has also been questioned [10, 44–46]. There is concern that for selected patients with early stage disease, complete excision of the rectum and mesorectal envelope may represent overtreatment of the cancer and expose the patient to unnecessary morbidity, if cure could be achieved without such a radical surgical approach. In this scenario, it appears as if local excision, in selected patients, may be a viable alternative. At the other end of the pathological spectrum, for patients with more locally advanced rectal cancer (LARC), TME surgery may also be inappropriate and a more radical approach may be required in order to achieve the desired R0 resection margin. In recent years, surgery for rectal cancer beyond the TME plane has also attracted interest as the boundaries of what is considered to be potentially resectable have widened [10, 47]. It may therefore be time for a paradigm shift in the way in which rectal cancer is conceptualised, such that the treatment of rectal cancer is separated into early tumours
Early rectal cancer is regarded to be Dukes’ stage A (T1/ T2 N0) disease. How to optimally manage malignant rectal polyps and early rectal cancer is a problem that colorectal MDTs are faced with ever more frequently, as more countries undertake population screening for colorectal cancer that identifies more early stage disease [48]. The proximity of the rectum to the anal canal lends itself to a variety of techniques to locally excise the tumour if it is deemed that formal TME/ELAPE surgical resection is not required. These include the following: endoscopic snare polypectomy, transanal excision for lower third rectal lesions and transanal endoscopic microsurgery (TEMS) for mid and upper rectal lesions. There is general agreement that the ideal tumours for local excision are ≤3 cm in diameter, have a favourable histological profile, superficial (Tis and/or T1N0), are located below the peritoneal reflection and involve no more than 40 % of the rectal circumference. The decision whether to treat a patient with apparent early rectal cancer by local excision or by formal surgical TME resection is problematic because local excision alone potentially undertreats a patient if all the malignant tissue has not been removed, including lymph node metastases. On the other hand, formal surgical segmental resection potentially overtreats the patient if there is no residual disease and exposes the patient to the risk of morbidity and mortality that accompanies surgical resection. In the setting of rectal cancer surgery, in addition to the standard surgical risks, there are other risks that need to be considered: there may be a need for a
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Fig. 3 Algorithm for the management of patients with rectal cancer
temporary or permanent stoma, rectal resection can have a deleterious impact on bowel function and continence if GI continuity is restored and there is a risk of pelvic nerve damage and sexual dysfunction associated with rectal mobilisation. Unfortunately, the available data to guide the decision about local or TME excision of rectal cancer is currently poor [49] but includes histopathological features of the cancer that may inform about the risk of nodal involvement or residual disease within the bowel wall. A detailed discussion of these features is beyond the scope of this manuscript but includes adequacy of excision of the tumour to a clearance of >1 mm, the differentiation of the tumour, lymphatic or vascular invasion, Haggit (in polypoid lesions) [50] or Kikuchi level (in sessile lesions) [51] and finally the suspicion of lymph node metastases on local imaging with MRI or ERUS. Two recent meta-analyses have compared TEMS to conventional surgery for stage I [52] and T1 [53] early rectal cancers. In these meta-analyses, TEMS was associated with lower early postoperative complication rates, higher local and distant recurrence rate but no difference in long-term overall survival [52, 53]. Therefore, based on the current limited available evidence, the use of local excision by TEMS/polypectomy/transanal excision seems appropriate in selected low-risk T1 rectal cancers. There are two currently recruiting trials (CARTS [44] and the UK TREC trial [45]) that may extend the use of TEMS with
neoadjuvant treatment beyond the treatment of early rectal cancer, both are evaluating the role of TEMS for advanced tumours by comparing preoperative chemoradiotherapy followed by TEMS excision with conventional TME surgery. Laparoscopic and Robotic TME/ELAPE Surgery TME resection is defined as en bloc excision of the rectum along with its surrounding fatty envelope containing lymphovascular tissue with preservation of the pelvic nerves. As described previously, it is currently the accepted standard of care for rectal cancer surgery. With refinement in technique and equipment, the laparoscopic approach is increasingly being used as an alternative to an open approach for rectal resections [54]. One of the principal difficulties of the laparoscopic approach is the limited space in the pelvis in which to operate, particularly in the male and with low-lying rectal tumours. Several case series and trials have demonstrated the safety and feasibility of the laparoscopic approach for rectal cancer [55–63]. These trials suggest that laparoscopic surgery affords similar oncological results to open surgery with less blood loss, have shorter recovery periods but take longer to perform. The role of robotics in colorectal surgery may be considered experimental at present, although it is gaining popularity. For colonic surgery, robotics is associated with a longer
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operative time and higher procedure cost compared to a laparoscopic approach; this is believed to be because colonic surgery usually requires dissection in different quadrants within the abdomen and each time the camera and operating instruments need to move necessitating a significant set up time. However, the stable camera system that is free of natural human tremors and use of articulated instruments may have a role in the tight fixed operating space of the pelvis. Results from a series of robotic TME suggest that it may allow better preservation of urinary and sexual functions [64]. A meta-analysis of eight non randomised studies of robotic versus laparoscopic rectal excision suggested that the conversion rate to open surgery in the robotic group was significantly lower than that with a laparoscopic surgery [65]. There were no significant differences in operation time, length of hospital stay, time to resume regular diet, postoperative morbidity and mortality, or the oncological accuracy of resection. The ROLARR trial is an ongoing pan-world RCT that is comparing robotic versus laparoscopic resection for rectal cancer that may guide future use of robotic surgery [66]. Locally Advanced Cancers Beyond the TME Plane Locally advanced rectal cancers (LARC) encroaching beyond the TME planes occurs in 10–20 % of rectal cancer patients and can pose a particular management challenge [67]. In this situation, complete surgical resection with an R0 resection will only be achieved through extended surgical resection beyond the TME plane. The fixed anatomy of the rectum in the pelvis is such that local tumour advancement beyond the TME plane will lead to contiguous organ involvement. Anterior advancement will lead to involvement of urological or reproductive organs; posterior advancement may involve the sacrum. In these scenarios, an R0 resection will only be achieved with en bloc multivisceral resection (MVR) or composite sacral resection. Extension of the tumour into the pelvic sidewalls can be particularly problematic but can sometimes be managed by en bloc iliac vessel and/or ureteric resection. The challenge posed by patients with LARC prompted a recent collaborative meeting of world experts in this field, who have developed a consensus statement to guide management [10]. The consensus statement from this meeting made several recommendations including those annotated below: & & & &
Patients with LARC should be managed by superspecialised MDTs. Most patients with LARC should receive preoperative neoadjuvant chemoradiotherapy. Extended surgery has a limited role in patients managed with palliative intent. Disease extension above the S2 level and into the pelvic
sidewall should be considered a relative contra-indication to surgery. Surgery for LARC is considered technically challenging and is associated with high peri-operative morbidity (typically over 40 %) and often results in hospital stays of between 10– 30 days [10, 67]. However, in a recent systematic review of 901 LARC patients treated by MVR, the 5-year overall survival was 52.8 %, suggesting that despite the peri-operative risk, it should be considered in suitable patients [67].
Conclusion In the last 30 years, significant improvements have been made in rectal cancer treatment with improved outcomes for patients; much of this progress has revolved around the use of standardised surgery in the TME plane with, more recently, wide perineal excision for patients undergoing APE. Whilst colorectal surgery worldwide is to be applauded for these improvements, there is a risk that rectal excision in this plane overtreats patients with early stage disease leading to unnecessary morbidity and at the other end of the pathological spectrum undertreats patients with locally advanced disease who would benefit from surgery beyond the TME plane. Is it therefore time to reconsider the way in which rectal cancers are conceptualised to include, “sub TME tumours” optimally treated by local excision +/− chemoradiotherapy, “TME tumours” best treated by standardised TME/ELAPE surgery and “beyond TME” tumours optimally treated by multivisceral extended surgery—a paradigm shift in rectal cancer treatment. Suggested algorithm for the management of rectal cancer is shown in Fig. 3.
Acknowledgments TEMS specimen image was provided by Mr. Stephan Korsgen, Consultant Colorectal Surgeon, Heart of England Foundation NHS Trust.
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56. Guillou PJ, Quirke P, Thorpe H, Walker J, Jayne DG, Smith AM et al (2005) Short-term endpoints of conventional versus laparoscopicassisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial. Lancet 365(9472): 1718–26 57. Hasegawa H, Ishii Y, Nishibori H, Endo T, Watanabe M, Kitajima M (2007) Short- and midterm outcomes of laparoscopic surgery compared for 131 patients with rectal and rectosigmoid cancer. Surg Endosc 21(6):920–4 58. Jayne DG, Guillou PJ, Thorpe H, Quirke P, Copeland J, Smith AM et al (2007) Randomized trial of laparoscopic-assisted resection of colorectal carcinoma: 3-year results of the UK MRC CLASICC Trial Group. J Clin Oncol 25(21):3061–8 59. Miyajima N, Fukunaga M, Hasegawa H, Tanaka J, Okuda J, Watanabe M, Japan Society of Laparoscopic Colorectal Surgery (2009) Results of a multicenter study of 1,057 cases of rectal cancer treated by laparoscopic surgery. Surg Endosc 23(1):113–8 60. Jayne DG, Thorpe HC, Copeland J, Quirke P, Brown JM, Guillou PJ (2010) Five-year follow-up of the Medical Research Council CLASICC trial of laparoscopically assisted versus open surgery for colorectal cancer. Br J Surg 97(11):1638–45 61. Kang SB, Park JW, Jeong SY, Nam BH, Choi HS, Kim DW et al (2010) Open versus laparoscopic surgery for mid or low rectal cancer after neoadjuvant chemoradiotherapy (COREAN trial): short-term outcomes of an open-label randomised controlled trial. Lancet Oncol 11(7):637–45 62. Green BL, Marshall HC, Collinson F, Quirke P, Guillou P, Jayne DG, Brown JM (2013) Long-term follow-up of the Medical Research Council CLASICC trial of conventional versus laparoscopically assisted resection in colorectal cancer. Br J Surg 100(1):75–82 63. Van der Pas MH, Haglind E, Cuesta MA, Fürst A, Lacy AM, Hop WC et al (2013) Laparoscopic versus open surgery for rectal cancer (COLOR II): short-term outcomes of a randomised, phase 3 trial. Lancet Oncol 14(3):210–8 64. D'Annibale A, Pernazza G, Monsellato I, Pende V, Lucandri G, Mazzocchi P, Alfano G (2013) Total mesorectal excision: a comparison of oncological and functional outcomes between robotic and laparoscopic surgery for rectal cancer. Surg Endosc 27(6):1887–95 65. Trastulli S, Farinella E, Cirocchi R, Cavaliere D, Avenia N, Sciannameo F et al (2012) Robotic resection compared with laparoscopic rectal resection for cancer: systematic review and metaanalysis of short-term outcome. Color Dis 14(4):e134–56 66. Collinson FJ, Jayne DG, Pigazzi A, Tsang C, Barrie JM, Edlin R et al (2012) An international, multicentre, prospective, randomised, controlled, unblinded, parallel-group trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer. Int J Color Dis 27(2):233–41 67. Mohan HM, Evans MD, Larkin JO, Beynon J, Winter DC (2013) Multivisceral resection in colorectal cancer: a systematic review. Ann Surg Oncol 20(9):2929–36
ORIGINAL ARTICLE
Paradigm Shift in the Management of Rectal Cancer Nihit Rawat & Martyn D. Evans
Received: 24 February 2014 / Accepted: 23 April 2014 # Association of Surgeons of India 2014
Abstract Surgery for rectal cancer in the pre-Total Mesorectal Excision (TME) era was associated with high local recurrence rates. The widespread adoption of the TME technique together with the addition of neoadjuvant oncological therapies have reduced local failure rates and improved survival for patients with rectal cancer. Advances in our knowledge, better understanding of tumour biology and refinement in minimal access techniques and equipment have significantly changed the management of rectal cancer. This paper reviews these changes and proposes a paradigm shift in how rectal cancer management is conceptualised and treated, such that the treatment of rectal cancer is separated into early tumours (potentially suitable for local excison), TME tumours (optimally managed by TME) and beyond TME tumours (optimally managed by multivisceral resection outside the TME plane). Keywords Chemoradiatherapy . Rectal cancer . Total mesorectal excision . Multivisceral resection
Introduction Worldwide, half a million patients are diagnosed with colorectal cancer each year, of which approximately one third are located in the rectum. In the last 30 years, the management of rectal cancer has been refined with improvements in surgical technique, radiological staging and use of neoadjuvant oncological treatment. A patient who presents with rectal cancer wants to be cured with as little impact on their quality of life as possible. It is N. Rawat Advanced Pelvic Oncology Fellow, Swansea Colorectal Unit, Swansea, UK M. D. Evans (*) Swansea Colorectal Unit, Colorectal Surgeon, Morriston Hospital, Heol Maes Eglwys, Morriston, Swansea SA6 6NL, UK e-mail: [email protected]
generally accepted that surgical resection with a clear circumferential margin will be required to achieve cure. Historically, surgery for rectal cancer was performed as expediently as possible by blunt blind dissection that yielded poor oncological results with high rates of local failure. In 1982, Heald reported the technique of total mesorectal excision (TME) that removed the rectal bowel tube along with the surrounding mesorectal envelope. Since, TME has been adopted worldwide as the surgical technique of choice to treat rectal cancer [1–3]. The use of TME has reduced local recurrence rates following surgery from 30 to under 10 % in large national audits [4]. Whilst surgery in the TME plane appears optimal for most rectal cancers, there is however, a problem in its use for tumours in the lower rectum at the level where the rectum goes through the pelvic floor. Tumours at this height are typically treated by abdominoperineal excision (APE). At this level, the mesorectum narrows; dissection in the TME plane therefore culminates in dissection between the levator ani muscles and the fascia propria of the rectum. This risk entering the tumour, which may lead to an involved circumferential resection margin (CRM) and greatly increases the risk of local recurrence [5]. Large national audits have demonstrated that the CRM involvement rates are far higher after APE than after anterior resection [6]. As a consequence of the high local failure rates in patients undergoing APE, the technique of extralevator abdominoperineal excision (ELAPE) has been promulgated by Holm. ELAPE involves wide excision of the pelvic floor en bloc with the rectum mobilised in the TME plane to the top of the pelvic floor [7]. Adoption of the ELAPE technique has been shown to reduce local recurrence rates after APE [8]. Whilst refinement of surgical techniques have improved outcomes from tumours treated by TME or ELAPE surgery, there are other developments that have also improved outcomes and surgical planning for tumours excised in the TME/ELAPE plane including: improved radiological staging, the use of neoadjuvant therapy and improvements in minimally invasive equipment and skills.
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Aside from TME/ELAPE surgery, our improved understanding of the pathology of early rectal cancer has led to increased use of local excision as a definitive treatment [9]. At the other end of the pathological spectrum, there has been a recent focus on the management of locally advanced rectal cancer (LARC) and performing surgical resection beyond the TME plane [10]. This paper reviews the developments in rectal cancer management over recent years and proposes a change in thinking about how rectal cancer management is conceptualised and treated.
Definition of the Rectum What constitutes the “rectum” is a contentious issue with differing surgical, radiological and anatomical definitions described. Anatomically, the rectum is 12–15 cm long and starts at the level of the S3 sacral vertebra and ends at the level of the anal canal [11]. Radiologically, judged on magnetic resonance imaging (MRI) criteria, the rectum is the portion of the large bowel below the level of the sacral promontory with a clearly definable mesorectum posteriorly [10]. From a surgical perspective, the rectum starts at the point of fusion of the two antemesenteric taenias on the sigmoid colon; this usually corresponds to the level of the sacral promontory. Whilst there are different definitions, it is important to have a clear definition of what constitutes a rectum because the treatment of rectal cancer differs from that of colonic cancer in some important areas, particularly in the use of peri-operative radiotherapy [12]. Consequently, in 1999, representatives of the American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland and Australian Societies met to agree on a definition of the rectal cancer. This resulted in rectal cancer being defined as any tumour whose distal margin is visible at or below 15 cm from the anal verge on rigid sigmoidoscopy [10, 12].
Preoperative Imaging All patients with rectal cancer should have staging investigations to assess the presence of synchronous tumours, local invasion, nodal disease and distant metastases. Therefore, all patients should have a complete large bowel evaluation; computed tomography (CT) scan of the chest, abdomen and pelvis to search for metastatic disease and MRI scan of the pelvis to locally stage the tumour and assess nodal and contiguous organ involvement. In some centres, endorectal ultrasonography (ERUS) is used as an alternative or in addition to MRI for local staging and may be particularly useful in the assessment of patients with mid and low early rectal cancer.
Computed Tomography (CT) All patients with rectal cancer should have a CT scan of the chest, abdomen and pelvis to assess local and distal spread of the disease [12, 13]. However, the role of CT in local staging of the primary tumour is limited by poor sensitivity and specificity for T stage and N stage when compared to ERUS and MRI [14, 15]. Therefore at the present time, the main role of CT is in the assessment of distant metastases. Magnetic Resonance Imaging (MRI) All patients being considered for surgical resection of rectal cancer should undergo MRI assessment. The rational for this is that MRI can predict the T and N stage of a rectal tumour more accurately than CT and is superior at identifying contiguous organ involvement, a threatened CRM or the presence of extra-mural vascular invasion, which may influence the decision to use neoadjuvant treatment [16–18]. Endorectal Ultrasound (ERUS) ERUS offers an alternative technique to MRI to stage the primary tumour and is particularly helpful in assessment of mid and low rectal tumours. Although ERUS is operator dependent, it is considered to be more accurate than MRI in defining T stage of early tumours (benign versus T1/2) and also in the distinction between T3 tumours which may influence the decision to give preoperative neoadjuvant therapy [14]. However, ERUS is considered to be inferior to MRI in the assessment of lymph node involvement and a threatened CRM although it has similar accuracy in the assessment of contiguous organ involvement [14]. A number of studies have attempted to establish whether MRI or ERUS is the more accurate modality to locally stage rectal cancer [19–21]. However, there does not appear to be a clear answer, as both have their merits and disadvantages. The authors believe that both may individually yield useful information that if used synergistically allows for optimal decisionmaking for the patient with rectal cancer, it is therefore our practice to use both in all patients treated with rectal cancer (Fig. 1).
Management of Rectal Cancer Once a patient with rectal cancer has been staged, the patient should be discussed in a colorectal cancer multidisciplinary team (MDT) meeting [22, 23]. Whilst up to 20 % of patients have metastases at presentation, usually making cure impossible, the majority of rectal cancer patients do not have metastases at presentation and are treated with curative intent and
Indian J Surg Fig. 1 Comparative ERUS and MR in a T4 rectal cancer invading prostate. ERUS and MRI images of the same patient. MR showed possible prostatic involvement, ERUS demonstrated unequivocal prostate involvement, demonstrating the advantage of multimodal imaging
surgery with or without neoadjuvant treatments (radiotherapy (RT) and chemotherapy) remains the mainstay of treatment. The Role of Preoperative Neoadjuvant Therapy The MDT management of rectal cancer with curative intent has changed in the last two decades; neoadjuvant oncological treatment, prior to TME/ELAPE surgery, are now commonly used with the aim of improved local disease control and survival in selected patients. It is accepted that preoperative radiotherapy is more efficacious than postoperative (adjuvant) treatment at achieving local control [24, 25]. The two widely accepted approaches to preoperative treatment are either short course preoperative radiotherapy (SCPRT) or long course chemoradiotherapy (CRT). A detailed discussion of these is beyond the scope of this manuscript but broadly, SCPRT has been advocated by some for most rectal cancers. CRT is generally considered for more advanced and lower third rectal cancers to try and downstage a tumour. The rational for SCPRT for most patients are the results of three large European trials [26–28] and the UK’s CR07 trial [24] that reported improved local control and possibly improved survival for rectal cancer patients treated with SCPRT against those treated with surgery alone. However, some of these trials have been criticised for the lack of TME surgical resection in the surgery arm and the benefit observed has been labelled secondary to the effect of RT compensating for poor surgical quality. Long course neoadjuvant CRT is generally utilised for the more advanced and lower third rectal cancers. The technique was evaluated in the German rectal cancer trial [25, 29], which randomised patients between preoperative treatment with 5FU and long course radiotherapy with the same chemoradiotherapy protocol administered postoperatively for patients with locally advanced rectal cancer (LARC). The trial reported improved local control and sphincter preservation with
preoperative chemoradiotherapy. However, there was no difference in overall survival [25, 29]. At the present time, the indications for radiotherapy in rectal cancer management are not standardised. Whilst the data from the European trials supports the use of SCPRT in all operable rectal cancers, its uptake in the UK has been variable. A recent UK national audit reported that the use of SCPRT in elective rectal cancer resections varied between MDTs, with a range of 0 to 30 % of patients having elective rectal resection for cancer [30]. Advocates for SCPRT argue that it should be given to all patients due to the improved local disease control demonstrated in the European trials. Opponents to SCPRT for all patients argue that the trials were compromised by poor quality surgery. These opponents also argue that radiotherapy is not without risk and may cause worse bowel function and increased urinary and sexual dysfunction in patients treated, and these risks need to be balanced against the potential benefit in terms of local control [31, 32]. In more advanced tumours, both SCPRT and CRT have been advocated. Trials comparing the two treatments suggest that CRT may increase downsizing and downstaging when compared to SCPRT, but this has not translated into improved long-term survival [33–35]. In light of these results in patients with more locally advanced tumours, in which the benefits of tumour downsizing outweigh the potential functional risks of radiotherapy, long course treatment appears to achieve better local control than short course radiation therapy and remains the preferred choice for locally advanced rectal cancers in most centres. The Role of Complete Response to CRT in Rectal Cancer Management Most series of patients treated with CRT include some who have a complete clinical and pathological response to
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treatment [36]. At present, subsequent surgical resection remains the standard of care even if a complete response is suspected. The rational for this is concern that there may be undetected microscopic disease or that the disease will recur [37]. There has however been interest in the work of HabrGama and colleagues who have reported their experience of observation rather than resection in patients who have a complete response [38]. They have also modified the standard CRT regimens to include additional chemotherapy during the resting period following long course radiotherapy to maximise the chance of a complete response. They have reported at a median follow up of 56 months that 50 % of their patients have not required surgical resection [39]. Based on this, they advocate a selective wait and watch approach for the patients with complete clinical response to neoadjuvant chemoradiotherapy [39]. Whilst Habr-Gama and colleagues have experienced very encouraging results, other series have not shown such high complete response rates and therefore until more evidence is available caution must be adopted in the widespread adoption of this technique [40–42].
Fig. 2 Specimen images of TEMS, total mesorectal excision and multivisceral resection
(potentially suitable for local excision), TME tumours (optimally managed by TME) and beyond TME tumours (optimally managed by multivisceral resection outside the TME plane) (Fig. 2).
Surgery for Rectal Cancer
Management of Early Rectal Cancer and the Malignant Polyp
Surgery with or without prior neoadjuvant therapy remains the mainstay of treatment of rectal cancer with curative intent. The goal of surgery in this setting is complete excision of the tumour, with a clear circumferential margin (R0). If this is achieved, the risk of local recurrence is minimised [43]. Whilst TME/ELAPE surgery is now an accepted standard of care in rectal cancer surgery, how this is performed has evolved with advances in laparoscopic and robotic equipment and expertise. Whether all patients with rectal cancer should be treated by TME/ELAPE surgery has also been questioned [10, 44–46]. There is concern that for selected patients with early stage disease, complete excision of the rectum and mesorectal envelope may represent overtreatment of the cancer and expose the patient to unnecessary morbidity, if cure could be achieved without such a radical surgical approach. In this scenario, it appears as if local excision, in selected patients, may be a viable alternative. At the other end of the pathological spectrum, for patients with more locally advanced rectal cancer (LARC), TME surgery may also be inappropriate and a more radical approach may be required in order to achieve the desired R0 resection margin. In recent years, surgery for rectal cancer beyond the TME plane has also attracted interest as the boundaries of what is considered to be potentially resectable have widened [10, 47]. It may therefore be time for a paradigm shift in the way in which rectal cancer is conceptualised, such that the treatment of rectal cancer is separated into early tumours
Early rectal cancer is regarded to be Dukes’ stage A (T1/ T2 N0) disease. How to optimally manage malignant rectal polyps and early rectal cancer is a problem that colorectal MDTs are faced with ever more frequently, as more countries undertake population screening for colorectal cancer that identifies more early stage disease [48]. The proximity of the rectum to the anal canal lends itself to a variety of techniques to locally excise the tumour if it is deemed that formal TME/ELAPE surgical resection is not required. These include the following: endoscopic snare polypectomy, transanal excision for lower third rectal lesions and transanal endoscopic microsurgery (TEMS) for mid and upper rectal lesions. There is general agreement that the ideal tumours for local excision are ≤3 cm in diameter, have a favourable histological profile, superficial (Tis and/or T1N0), are located below the peritoneal reflection and involve no more than 40 % of the rectal circumference. The decision whether to treat a patient with apparent early rectal cancer by local excision or by formal surgical TME resection is problematic because local excision alone potentially undertreats a patient if all the malignant tissue has not been removed, including lymph node metastases. On the other hand, formal surgical segmental resection potentially overtreats the patient if there is no residual disease and exposes the patient to the risk of morbidity and mortality that accompanies surgical resection. In the setting of rectal cancer surgery, in addition to the standard surgical risks, there are other risks that need to be considered: there may be a need for a
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Fig. 3 Algorithm for the management of patients with rectal cancer
temporary or permanent stoma, rectal resection can have a deleterious impact on bowel function and continence if GI continuity is restored and there is a risk of pelvic nerve damage and sexual dysfunction associated with rectal mobilisation. Unfortunately, the available data to guide the decision about local or TME excision of rectal cancer is currently poor [49] but includes histopathological features of the cancer that may inform about the risk of nodal involvement or residual disease within the bowel wall. A detailed discussion of these features is beyond the scope of this manuscript but includes adequacy of excision of the tumour to a clearance of >1 mm, the differentiation of the tumour, lymphatic or vascular invasion, Haggit (in polypoid lesions) [50] or Kikuchi level (in sessile lesions) [51] and finally the suspicion of lymph node metastases on local imaging with MRI or ERUS. Two recent meta-analyses have compared TEMS to conventional surgery for stage I [52] and T1 [53] early rectal cancers. In these meta-analyses, TEMS was associated with lower early postoperative complication rates, higher local and distant recurrence rate but no difference in long-term overall survival [52, 53]. Therefore, based on the current limited available evidence, the use of local excision by TEMS/polypectomy/transanal excision seems appropriate in selected low-risk T1 rectal cancers. There are two currently recruiting trials (CARTS [44] and the UK TREC trial [45]) that may extend the use of TEMS with
neoadjuvant treatment beyond the treatment of early rectal cancer, both are evaluating the role of TEMS for advanced tumours by comparing preoperative chemoradiotherapy followed by TEMS excision with conventional TME surgery. Laparoscopic and Robotic TME/ELAPE Surgery TME resection is defined as en bloc excision of the rectum along with its surrounding fatty envelope containing lymphovascular tissue with preservation of the pelvic nerves. As described previously, it is currently the accepted standard of care for rectal cancer surgery. With refinement in technique and equipment, the laparoscopic approach is increasingly being used as an alternative to an open approach for rectal resections [54]. One of the principal difficulties of the laparoscopic approach is the limited space in the pelvis in which to operate, particularly in the male and with low-lying rectal tumours. Several case series and trials have demonstrated the safety and feasibility of the laparoscopic approach for rectal cancer [55–63]. These trials suggest that laparoscopic surgery affords similar oncological results to open surgery with less blood loss, have shorter recovery periods but take longer to perform. The role of robotics in colorectal surgery may be considered experimental at present, although it is gaining popularity. For colonic surgery, robotics is associated with a longer
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operative time and higher procedure cost compared to a laparoscopic approach; this is believed to be because colonic surgery usually requires dissection in different quadrants within the abdomen and each time the camera and operating instruments need to move necessitating a significant set up time. However, the stable camera system that is free of natural human tremors and use of articulated instruments may have a role in the tight fixed operating space of the pelvis. Results from a series of robotic TME suggest that it may allow better preservation of urinary and sexual functions [64]. A meta-analysis of eight non randomised studies of robotic versus laparoscopic rectal excision suggested that the conversion rate to open surgery in the robotic group was significantly lower than that with a laparoscopic surgery [65]. There were no significant differences in operation time, length of hospital stay, time to resume regular diet, postoperative morbidity and mortality, or the oncological accuracy of resection. The ROLARR trial is an ongoing pan-world RCT that is comparing robotic versus laparoscopic resection for rectal cancer that may guide future use of robotic surgery [66]. Locally Advanced Cancers Beyond the TME Plane Locally advanced rectal cancers (LARC) encroaching beyond the TME planes occurs in 10–20 % of rectal cancer patients and can pose a particular management challenge [67]. In this situation, complete surgical resection with an R0 resection will only be achieved through extended surgical resection beyond the TME plane. The fixed anatomy of the rectum in the pelvis is such that local tumour advancement beyond the TME plane will lead to contiguous organ involvement. Anterior advancement will lead to involvement of urological or reproductive organs; posterior advancement may involve the sacrum. In these scenarios, an R0 resection will only be achieved with en bloc multivisceral resection (MVR) or composite sacral resection. Extension of the tumour into the pelvic sidewalls can be particularly problematic but can sometimes be managed by en bloc iliac vessel and/or ureteric resection. The challenge posed by patients with LARC prompted a recent collaborative meeting of world experts in this field, who have developed a consensus statement to guide management [10]. The consensus statement from this meeting made several recommendations including those annotated below: & & & &
Patients with LARC should be managed by superspecialised MDTs. Most patients with LARC should receive preoperative neoadjuvant chemoradiotherapy. Extended surgery has a limited role in patients managed with palliative intent. Disease extension above the S2 level and into the pelvic
sidewall should be considered a relative contra-indication to surgery. Surgery for LARC is considered technically challenging and is associated with high peri-operative morbidity (typically over 40 %) and often results in hospital stays of between 10– 30 days [10, 67]. However, in a recent systematic review of 901 LARC patients treated by MVR, the 5-year overall survival was 52.8 %, suggesting that despite the peri-operative risk, it should be considered in suitable patients [67].
Conclusion In the last 30 years, significant improvements have been made in rectal cancer treatment with improved outcomes for patients; much of this progress has revolved around the use of standardised surgery in the TME plane with, more recently, wide perineal excision for patients undergoing APE. Whilst colorectal surgery worldwide is to be applauded for these improvements, there is a risk that rectal excision in this plane overtreats patients with early stage disease leading to unnecessary morbidity and at the other end of the pathological spectrum undertreats patients with locally advanced disease who would benefit from surgery beyond the TME plane. Is it therefore time to reconsider the way in which rectal cancers are conceptualised to include, “sub TME tumours” optimally treated by local excision +/− chemoradiotherapy, “TME tumours” best treated by standardised TME/ELAPE surgery and “beyond TME” tumours optimally treated by multivisceral extended surgery—a paradigm shift in rectal cancer treatment. Suggested algorithm for the management of rectal cancer is shown in Fig. 3.
Acknowledgments TEMS specimen image was provided by Mr. Stephan Korsgen, Consultant Colorectal Surgeon, Heart of England Foundation NHS Trust.
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