New Updates in Diagnostic Imaging and Treatment of Rectal Cancer.

Locally advanced rectal adenocarcinoma: Treatment sequences, intensification, and rectal organ preservation.

The American Society of Colon and Rectal Surgeons Clinical Practice Guidelines for the Management of Rectal Cancer.

The primary curative modality for localized rectal cancer is total mesorectal excision (TME). Local control rate of rectal cancer has been improved after neoadjuvant chemoradiotherapy and even pathological complete response (pCR) has been demonstrated in a significant minority. Patients who achieve pCR to neoadjuvant chemoradiotherapy have an excellent prognosis compared with those without pCR. If the patients with complete response to neoadjuvant chemoradiation can be demonstrated by clinical findings and medical imaging (cCR), a non-operative management (NOM) strategy may be pursued to preserve sphincter function and avoid complications induced by TME, which is a new tendency in the treatment of rectal cancer in recent years. Assisting diagnosis of cCR by iconography is the important element of NOM practice. Selected patients should be followed up with intensive surveillance. The curative strategy must be carried out once the recurrence is detected. Imaging modalities, including magnetic resonance imaging (MRI), diffusion-weighted MRI, or proton emission tomography (PET), are limited in their ability to distinguish patients who have achieved cCR. Up to now, MRI, DW-MRI and 18F-FDG PET/CT before neoadjuvant chemoradiotherapy are not accurate enough to predict cCR and safely select patients for organ-sparing strategies. However, depth of tumor infiltration, extramural vascular invasion, circumferential resection margin, and location of rectal cancer can be demonstrated by high resolution MRI as independent risk factors in prediction of long-term survival of patients, which is a necessary manner of stratification treatment for rectal cancer. Therefore, patients who are defined as early rectal cancer with low risk factors are selected as candidates for NOM in recent studies in order to pursue low rate of local recurrence and distant metastasis. High resolution MRI assessment of tumor regression grade (mrTRG) can be used to assess response of rectal cancer to neoadjuvant chemoradiotherapy, which is associated with tumor burden. mrTRG is an imaging marker that indicates the difference in survival between good and poor responders and provides an opportunity for the multidisciplinary team to offer additional treatment options before planning definitive surgery. Functional imaging and even molecular imaging are needed in the future to screen suitable rectal cancer patients who are easier to achieve cCR from neoadjuvant chemoradiotherapy and to evaluate the efficacy of neoadjuvant chemoradiotherapy.

Role of endoscopy in the staging and management of colorectal cancer

Magnet-Resonanz-Tomographie-Diagnostik beim fortgeschrittenen Rektumkarzinom (UICC II bis IV) vor und nach neoadjuvanter Radio-/Chemotherapie - Stellenwert aus chirurgischer Sicht

Combined modality therapy for rectal cancer

Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.

Rectal cancer is one of the most common malignancies in China. Neoadjuvant chemoradiotherapy combined with total mesorectal excision is the standard treatment of locally advanced rectal cancer. Magnetic resonance imaging (MRI) can provide anatomical positioning, clinical staging and evaluation of clinical efficacy of neoadjuvant chemoradiotherapy, thereby offering support for the precise establishment of comprehensive therapeutic strategy. This study aims to summarize the current status and development trend of MRI applied in the staging of rectal cancer, evaluation and prediction of clinical efficacy. Key words: Rectal neoplasm/neoadjuvant chemoradiotherapy; Magnetic resonance imaging

Background: In this era of total neoadjuvant treatment (TNT) followed by rectal preservation non-operative management (NOM) or wait and watch (WW) approach for non-metastatic locally-advanced rectal cancer (LARC), reliable and reproducible response evaluation to neoadjuvant therapies forms the cornerstone. Through this study, we try to evaluate clinical response of locally-advanced rectal cancer to neoadjuvant chemoradiation (CRT) in terms of downstaging and total mesorectal excision (TME), and the accuracy of digital rectal examination (DRE), magnetic resonance imaging (MRI) and colonoscopy in the assessment of clinical response to neoadjuvant CRT. Methods: Histologically proven locally advanced rectal adenocarcinoma patients, after pretreatment evaluation, were considered for neoadjuvant chemoradiation, i.e., intensity-modulated radiation therapy (IMRT) with 5-fluorouracil (5-FU) and leucovorin-based concurrent chemotherapy. Patients were evaluated 6-8 weeks after completion of CRT and clinical response assessed by means of DRE, colonoscopy and MRI of pelvis. Following surgery, pathological response was assessed on the final histopathological examination (HPE). Results: Twenty-two patients were accrued for this protocol, of which, 15 (68.2%) were male and 7 (31.8%) were female. Downstaging and TME was achieved in 90.9% of the patients. The sensitivity of DRE, colonoscopy and MRI to detect a complete response was 66.67% and specificity was 94.74%. There were no severe toxicities or deaths reported. Conclusions: Neoadjuvant concurrent chemoradiotherapy with bolus 5-FU and leucovorin is an accepted modality of treatment for locoregionally-advanced rectal cancer, which offers higher rates of downstaging and TME. Digital rectal examination, colonoscopy and MRI together can be reliably used to assess response following neoadjuvant CRT.

Carcinoma of the rectum, a common malignancy in developed countries, accounts for approximately one third of colorectal cancers. Although majority of the localized rectal cancers are potentially curable, local recurrence remains a serious problem with severe disability and impaired quality of life. Rectal cancer, which was a surgically-managed tumour, now requires the coordinated efforts of multidisciplinary team, colorectal surgery, radiation oncology, medical oncology, radiology and others. In addition to the staging workup, pre-treatment evaluation of the local disease, by endorectal ultrasound (EUS) and multislice computer tomography (CT) and magnetic resonance imaging (MRI), is utmost important to determine the surgical approach and the need for the various other treatment modalities: radiation and chemotherapy (ChT). The introduction of Total Mesorectal Excision (TME) and neoadjuvant Radiation Therapy (RT) have led to significant improvement in the loco-regional control of the rectal cancer, 90–94%. TME is now widely accepted as the standard surgical technique for rectal cancer. Local recurrence rates have been shown to decrease significantly with TME alone. However, the addition of radiation therapy has furthered this improvement, especially in patients having a circumferential resection margin (CRM) that is involved with tumour on pre-operative imaging. There are two radiation modalities used in the treatment of patients with solid tumours, external beam radiation (EBRT) and brachytherapy (BT). In rectal cancer EBRT is primarily used to optimize the rate of local control achieved by surgery. Numerous clinical trials have confirmed its benefit, with or without chemotherapy, in improving local control. However, the survival advantage and the impact on distant metastasis are controversial. In view of normal organ toxicity associated with EBRT, newer radiation delivery techniques have been explored. High dose rate brachytherapy (HDRB) delivers radiation by an endoluminal approach, avoiding the delivery through other organs, and as such, decreases normal organ toxicity. The emerging prospective data are very promising and an international phase III study is being conducted. Despite significant improvement in local control, over the last decade, one third of the patients continue to fail at distance, with metastases. The role of chemotherapy in conjunction with radiation therapy as a neo-adjuvant modality to TME has been, mostly, accepted as routine in North America. However, to date, evidence from Phase III-randomized studies in rectal cancer fails to demonstrate any benefit from additional post-operative adjuvant 5-fluorouracil (FU)-based chemotherapy in terms of disease-free or overall survival in locally advanced rectal cancer. There have been significant achievements in the treatment of rectal cancer over the past decade with multidisciplinary approach becoming the standard of care. Such approach allows for the selection of those patients who are cured with surgery alone, as well as those at risk for failing locally, thus achieving a balance between treatment toxicity risks and tumour control gains.

Updates and Debate issues form the surgical treatment of middle or low rectal cancer The main goals for the surgical treatment of rectal cancer were the complete removal of the rectal cancer with surrounding lymphatic draining area, which subsequently result in decreasing the rate of local recurrence as well as prolong patient survival. If the tumor located at the near the anal canal, concerning issues will be whether anal sphincter can be preserved or not and furthermore autonomic pelvic nervous system could be saved or not. Multidisciplinary approach for rectal cancer has been more popular and treatment strategy rapidly changing based on more accurate preoperative local staging finding and minimal invasive surgical techniques become popular too. One of the advance technology is the development of transanal local excision techniques such Transanal endoscopic microsurgery technique such as TEM(transendoscopic microsurgery), TEO(transendoscopic operation) and TAMIS (transanal minimal invasive surgery). Those techniques make us be able to excise early rectal cancer with full thickness as well as unfragmented state, also can be approached to the upper rectum, which can not approach with previous conventional transanal approach method. Local excision for early T1 rectal cancer has been regards as good treatment option because patient can avoid complication related to the radial proctotectomy such as anastomoitc leakage, postoperative sexual and voiding dysfunction and dysregulated bowel movements. Neoadjuvant chemoradiation therapy has been recommended for patient with cT3N0 or cT3 N+ rectal cancer because some clinical trials showed us preoperative chemoradiation therapy showed better local control rate and less toxicities than postoperative chemoradiation treatment. Recent clinical trial both retrospective and prospective showed us a promising results about local excision after neoadjuvant chemoradiation selectively in patients with low rectal cancer. Neoadjuvant chemoradiation therapy for cT2N0 followed by local excision reported excellent oncologic outcomes quite comparable to the radical surgery group. In addition to that, there has been some reports which showed clinical complete remission after neoadjuvant chemoradiation therapy could be wait and see. A couple of observational studies showed wait and see can be possible option of treatment in selective patients. Radial surgery for middle and low rectal cancer still remains a cornerstone of surgical treatment Ultralow anterior resection with or without intersphincteric resection became a more standard surgical method for low rectal cancer. Oncologic and functional outcomes has been reported as safe even functional outcomes study was rare. Furthermore, Abdominoperineal resection has been famous for high intraoperative tumor perforation and positive circumferential resection margin, those factors have been contributed to the high rate of local recurrence and poor survival rate compared with sphincter saving procedures for rectal cancer. Recently, there have been great efforts for reducing theses problem and total levator excision or extended abdominoperineal resection concepts emerged. Surgeons who advocated this concept recommended perineal dissection under the Jack-knife position. Surgical management for low rectal cancer should be directed for radically and preserving function based on multimodality approach. We need more high level of evidence based on prospective clinical trials for tailored treatment of rectal cancer patients

CancerVolume 78, Issue 9 p. 1847-1850 EditorialFree Access Designing the optimal surgery for rectal carcinoma Warren E. Enker M.D., Corresponding Author Warren E. Enker M.D. Department of Surgery, and Division of Colorectal Surgery, Beth Israel Medical Center, New York, New York.350 East 17th Street, Baird Hall 1622, New York, NY 10003===Search for more papers by this author Warren E. Enker M.D., Corresponding Author Warren E. Enker M.D. Department of Surgery, and Division of Colorectal Surgery, Beth Israel Medical Center, New York, New York.350 East 17th Street, Baird Hall 1622, New York, NY 10003===Search for more papers by this author First published: 1 November 1996 https://doi.org/10.1002/(SICI)1097-0142(19961101)78:9<1847::AID-CNCR1>3.0.CO;2-CCitations: 23AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 Enker WE, Laffer UT, Block GE. Enhanced survival of patients with colon and rectal cancer is based upon wide anatomic resection. Ann Surg 1979; 190: 350– 60. 2 Heald RJ. A new approach to rectal cancer. Br J Hosp Med 1979; 277. 3 Sugihara K, Moriya Y, Akasu T, Fujita S. Pelvic autonomic nerve preservation for patients with rectal carcinoma: oncologic and functional outcome. Cancer 1996; 78: 1871– 80. 4 Church JM, Raudkivi PJ, Hill GL. The surgical anatomy of the rectum: a review with particular relevance to the hazards of rectal mobilization. Int J Colorectal Dis 1987; 2: 158– 66. 5 Beart RW, Steele GD, Menck HR, Chmiel JS, Ocwieja KE, Winchester DP. Management and survival of patients with adenocarcinoma of the colon and rectum: a national survey of the Commission on Cancer. J Am Coll Surg 1995; 181: 225– 36. 6 Enker WE, Thaler HT, Cranor ML, Polyak T. Total mesorectal excision in the operative treatment of rectal cancer. J Am Coll Surg 1995; 181: 335– 46. 7 Heald RJ, Husband EM, Ryall RDH. The mesorectum in rectal cancer surgery: the clue to pelvic recurrence. Br J Surg 1982; 69: 613– 6. 8 Quirke P, Durdey P, Dixon MF, Williams NS. Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumor spread and surgical excision. Lancet 1986; 1: 996– 9. 9 Adam IJ, McHamdee MO, Martin IG. et al. Role of circumferential margin involvement in the local recurrence of rectal cancer. Lancet 1994; 344: 707– 11. 10 Paty PB, Enker WE, Cohen AM, Lauwers GY. Treatment of rectal cancer by low anterior resection with coloanal anastomosis. Ann Surg 1994; 219: 365– 73. 11 MacFarlane J, Ryall RDH, Heald RJ. Mesorectal excision for rectal cancer. Lancet 1993; 341: 457– 60. 12 Enker WE. Potency, cure, and local control in the operative treatment of rectal cancer. Arch Surg 1992; 127: 1396– 1402. 13 Havenga K, Enker WE, McDermott K, Cohen AM, Minsky BD, Guillem J. Male and female sexual and urinary function after total mesorectal excision with autonomic nerve preservation for carcinoma of the rectum. J Am Coll Surg 1996; 182: 495– 502. 14 Minsky BD. Preoperative combined modality treatment for rectal cancer. Oncology 1994; 8: 53– 8. 15 Swedish Rectal Cancer Trial. Local recurrence rates in a randomized multiculture trial of preoperative radiotherapy compared with operation alone in resectable rectal carcinoma. Eur J Surg 1996; 162: 397– 402. 16 Stockholm Colorectal Cancer Study Group. Randomized study on preoperative radiotherapy in rectal carcinoma. Ann Surg Oncology 1996; 3: 423– 30. 17 Dutch Colorectal Cancer Group. Total mesorectal excision (TME) with or without preoperative readiotherapy in the treatment of primary rectal cancer. A multicenter phase III study. January 1996. 18 Norstein J, Bergan A, Langmark F. Risk factors for local recurrence after radical surgery for rectal carcinoma: a prospective multicentre study. Br J Surg 1993; 80 (Suppl): 22. 19 Quirke P. The pathologist's role in the evaluation of local recurrence in rectal cancer. In: Surgical Workshop and Prosection Course, Royal College of Surgeons of London, London, United Kingdom, April 25–26, 1995. Citing Literature Volume78, Issue91 November 1996Pages 1847-1850 ReferencesRelatedInformation

376 Background: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Methods: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Results: In the training set, 77.1% of patients had locally advanced stage by pathology. The multivariate analysis indicated that tumor size (Odds ratio (OR)=1.55, p&lt; 0.001), differentiation (OR =0.38, p&lt; 0.001), location (OR =1.06, p=0.038), serum CEA (OR =0.24, p&lt; 0.001) and CA19-9 level (OR =0.13, p&lt; 0.001) were associated with tumor stage. A nomogram consisting of these 5 factors was developed and predicted locally advanced stage with a concordance index of 0.756. The concordance index of this nomogram was 0.800 in the validation set. Conclusions: Large tumor size, far from anal verge, poor differentiation, elevated serum CEA and CA19-9 level were high-risk factors of locally advanced stage of rectal cancer. The nomogram based on these clinical factors can predicte locally advanced rectal cancer with a considerable accuracy and thus helpful for making neoadjuvant therapy recommendations.

Because favorable effects on survival were seen in randomized trials conducted during the 1980s, adjuvant chemotherapy in colon cancer was established as routine therapy in stage III disease in the United States in 1990. Follow-up trials in the United States, Asia, and Europe soon meant that it became recommended therapy worldwide, not only in stage III but in stage II disease as well, if risk factors for recurrence were present. Additional trials established the combination of a fluoropyrimidine and oxaliplatin as reference treatment for patients with stage II disease with risk factors who are fit for therapy and for those with stage III disease. The addition of oxaliplatin in the treatment of elderly patients has been questioned. Here we present arguments questioning not only the addition of oxaliplatin in the treatment of some younger patients as well but also the offering of adjuvant chemotherapy at all to some of these patients. Medical care continuously develops, and as a consequence, treatment results improve. This development has also been seen in colon (and rectal) cancer, and the improvements actually challenge the established benefit of adjuvant chemotherapy in colon (and rectal) cancer. We question whether the risk of recurrence is sufficiently high for most patients with stage II disease, even when risk factors are present, and for some patients with stage III disease in the presence of high-quality, modern, multidisciplinary team care to motivate adjuvant chemotherapy. In colorectal cancer, there has been a marked change during the past decades regarding surgery. It started with the total mesorectal excision (TME) technique for rectal cancer. This technique has now spread around the world; the majority of surgeons have learned how to operate effectively on rectal cancer, and many centers report low local recurrence rates. Population-based data from national quality registers also show that the local recurrence rate can today reach approximately 5%, equaling the rates achieved in dedicated centers. Surgery for colon cancer may also be about to change, with complete mesocolic excision dissection and the concept of central ligation. These techniques have started to spread among surgeons, and population data already indicate that there may be an overall survival benefit, in addition to improvements reflecting stage migration, if colonic surgery is performed in accordance with such procedures. Preoperative staging of colorectal cancer has also improved, and up-to-date contrast-enhanced computed tomography of the thorax and abdomen, completed with ultrasonography or magnetic resonance imaging with contrast agents in the case of equivocal liver lesions or positron emission tomography– computed tomography in the case of equivocal findings outside the liver, has also resulted in fewer recurrences in those undergoing surgery (ie, the target patients for adjuvant therapy). The scenario has changed from fewer metachronous to more synchronous metastases. Furthermore, although pathologists cannot reduce recurrence risks per se, better pathologic staging results in lower stage-specific recurrence rates, often referred to as stage migration. The rectal cancer radiotherapy story illustrates the same kind of problem the medical community is facing when one or several aspects of multidisciplinary care are improved. The story is well known from literature. The reduction in local recurrence rates seen after preoperative radiotherapy was questioned when surgery was improved (ie, when TME was introduced). The two trials then initiated—the Dutch–Swedish TME trial and the Medical Research Council CR07 trial in the United Kingdom, in which preoperative radiotherapy using the 5 3 5 Gy schedule was tested against selective postoperative (chemo)radiotherapy—showed that preoperative radiotherapy significantly reduced local recurrence rates. Actually, the relative reduction may have been slightly larger with TME (hazard ratio, 0.38; absolute difference, 11% v 4%) than with the older, suboptimal surgery (hazard ratio, 0.46; absolute difference, 27% v 13%). The overall survival gain seen previously in the Swedish Rectal Cancer Trial could not be reproduced; the absolute gain in local recurrences was likely too small to show up in the trials in which TME was used. The gains from postoperative chemoradiotherapy in local recurrence rates and survival have not been tested using TME. In a German trial testing preversus postoperative chemoradiotherapy, it was shown that preoperative chemoradiotherapy was better than postoperative in reducing the local recurrence rate, approximately 10% after postoperative treatment versus 7% after preoperative irradiation. The TME technique was used for most patients in the trial, but no difference in survival could be seen even after long-term follow-up. On the basis of this knowledge, there is an ongoing debate over whether radiotherapy is needed in the majority of rectal cancers because of the low recurrence rates seen today without

Before total mesorectal excision (TME) and radiation therapy/chemoradiation therapy (RT/CRT) were widely adopted in the treatment of rectal cancer, surgery alone was the standard. Therapies have since evolved to neoadjuvant RT or CRT followed by TME as the established paradigm for locally advanced disease. More recently, issues of toxicity and systemic metastasis have risen to the forefront, prompting the exploration of individualized strategies in an attempt to maximize potential cure and local control yet minimize late toxicities. In this article, we will focus on the treatment of high rectal cancers, exploring the specific role of pelvic radiotherapy in this setting.