- Email: [email protected]
Multimodality Treatment and Timing for Rectal Cancer in Hereditary Colorectal Cancer Patients
Multimodality Treatment and Timing for Rectal Cancer in Hereditary Colorectal Cancer Patients Aram N. Demirjian, MD, and Jonathan E. Efron, MD, FACS, FASCRS The management of rectal cancer is complex enough in itself but even more complicated in the setting of a hereditary cancer syndrome. Although the cancer treatment as such is similar to the one in sporadic cancer and based on cancer stage, tumor location, the patient’s overall presentation and condition, the presence of an underlying disease raises additional concerns about functional aspects and the risk of metachronous lesions. We reviewed the role of multimodality treatment and the timing and extent of the planned surgeries. Rectal cancer in the setting of hereditary cancer syndromes (eg, hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis) is not genuinely handled with a different approach, except when an ileal pouch anal anastomosis is planned as the neo-adjuvant modality should always be chosen to avoid the detrimental effect of radiation on an ileal pouch. Semin Colon Rectal Surg 22:137-140 © 2011 Elsevier Inc. All rights reserved.
R
ectal cancer is a significant cause of morbidity and mortality in the United States, with more than 39,600 new cases expected this year, and just more than 51,000 deaths from both colon and rectal cancer combined.1 Overall, rectal adenocarcinoma accounts for nearly 30% of all colorectal cancer (CRC).2 Treatment of rectal cancer is complex and differs from colon cancer in that there is significant interplay of the varying therapeutic modalities. Timing of chemotherapy, radiotherapy, and surgery depend on the overall clinical scenario. In addition, the type of surgery planned is governed by several factors, mainly the oncological outcome, along with quality of life aspects, such as sphincter preservation. Although most CRC cases are of sporadic origin, an estimated 20% of patients have some type of familial inheritance of their disease, and approximately 5% experience a welldefined hereditary syndrome,3 for example, hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), MYH-associated polyposis, or the hamartomatous polyposis syndromes.4 HNPCC and FAP are the most common of these syndromes and represent 2 fairly distinct clinical scenarios that might alter the typical paradigms of rectal cancer treatment. The goal of this review is to discuss
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD. Address reprint requests to: Jonathan E. Efron, MD, FACS, FASCRS, Department of Surgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 656, Baltimore, MD 21287. E-mail: [email protected]
1043-1489/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.scrs.2010.12.016
the nuances of treating rectal cancer that arises in the background of hereditary CRC, with a focus on HNPCC and FAP.
Hereditary Nonpolyposis Colorectal Cancer HNPCC is the most common of the inherited CRC syndromes, accounting for between 2% and 5% of all cases of CRC.5,6 It is autosomal dominant with a mutation in the DNA mismatch-repair gene system (almost two-thirds of cases are caused by a mutation in either MSH2 or MLH1) that is associated with microsatellite instability.7 In this setting, on average, presents approximately 20 years earlier than sporadic CRC,7 although newer data suggest that the average age at the time of diagnosis may be closer to 60.8 In comparison with FAP, HNPCC can present a more complex diagnostic quandary: there is typically no readily apparent polyposis, and the overall lifetime risk of developing CRC is at least 50%-60%.4 Diagnostic tools for HNPCC are the Amsterdam II criteria and the Revised Bethesda Guidelines as impetus to perform genetic testing.4 Patients with suspected or confirmed HNPCC should be screened with colonoscopy from their mid20s with at least yearly examinations,9 as the polyp-to-cancer transformation is significantly accelerated.10 CRC in HNPCC are “right-sided” (proximal to the splenic flexure) 70% of the time.4,11 However, a couple of retrospective studies have demonstrated that a rectal carcinoma may be the actual index or primary lesion in 21%-29% of HNPCC cases.5,12 The 3 factors that impact the choices for treatment 137
A.N. Demirjian and J.E. Efron
138 are (a) the location and stage of the primary tumor(s), (b) the risk for metachronous lesions, and (c) the functional aspects. In the setting of HNPCC, risk-reducing surgery is an attractive option as long as the rectum can be preserved, ie, for cases with colon cancer. As in cases of sporadic rectal cancer, surgical treatment options for rectal index lesions in HNPCC include on rare occasions a local excision, and most commonly an oncological resection (low-anterior resection, abdominoperineal resection, proctocolectomy with ileal pouch anal anastomosis [IPAA], or an end ileostomy). One of the key questions is the incidence of metachronous lesions in patients with a rectal cancer as their primary lesion. The authors of 2 retrospective studies demonstrated a very disparate incidence of a second colon cancer. In a study from the Roswell Park Cancer Institute in Buffalo, the incidence was 17% after a mean interval of 201 months.5 In contrast Möslein et al12 from Germany reported a much higher number of 54%, after a mean latency period of 7.4 years. It is difficult to determine the reason for these differences, but one should caution that both studies were retrospective and entailed only small groups of patients from 1 institution. The question of the true risk of metachronous lesions and which of the 2 reports more accurately reflects the incidence is critical: ●
●
If the 17% incidence is accurate, it may be prudent to treat HNPCC patients the same as sporadic rectal cancer patients. This would most commonly involve stage-dependent neoadjuvant chemoradiation, followed by an oncological resection. It is important to note that neoadjuvant radiation has been associated with a negative impact on the sphincter function, which is particularly important in cases where the baseline tone is diminished.13 If the number, however, is closer to one-half of all patients, the first approach with colonoscopic surveillance remains an option, but the alternative of a prophylactic procedure beyond the curative resection should be discussed with the patient. The later would involve a proctocolectomy with IPAA or an end ileostomy. Undoubtedly, the bowel frequency and function after an IPAA would differ significantly from normal or a low-anterior resection or colo-anal anastomosis. The cancer risk needs to be weighed against the patient’s quality of life.
Familial Adenomatous Polyposis FAP results from an autosomal-dominant germline mutation in the APC gene. It is characterized by the development of multiple adenomatous polyps beginning from the second life decade14,15 and a near 100% progression to CRC by the fourth or fifth decade of life if untreated.16 However, it only accounts for ⬍1% of all CRC.4 Surgical resection in prophylactic or therapeutic intent has evolved as the most important concept for this disease since the 1930s.17 It is not clear from the literature how often rectal cancers present as the index lesion. Much more attention has been paid to the concern
developing rectal cancer following prophylactic surgery. For the decision between ileo-rectal anastomosis and IPAA, 2 aspects have to be balanced: ●
●
obtaining a satisfactory oncological (or more accurately prophylactic) outcome, including the need for surveillance and potential subsequent surgeries; and achieving an acceptable functional result.
Preserving the rectum through the use of ileo-rectal anastomosis might create a better functional outcome for patients as measured by lower numbers of total daily bowel motions, a decreased need to use absorbent undergarment pads, and less frequent nighttime accidents18; increased confidence in one’s body image; or increase in sexual function.19 The flip side of rectal preservation is the subsequent risk of developing a rectal cancer, which overall has to be considered significant with a range from 5% at 5 years up to 59% after 23 years,20,21 even if lower numbers were reported by others.22 The factors that correlate best with increased risk are the number of rectal polyps greater than 10-20,23,24 patient age, polyp size ⬎1 cm, length of the rectal stump, the presence of cancer in the original colonic specimen, and the compliance with stump surveillance.24-29 Although endoscopic surveillance is perceived as being safe and effective,24,30 investigators from a larger population-based study from northern Europe questioned it adequacy. Vasen et al31 reported that 75% of patients who eventually developed rectal cancer had an endoscopy within 12 months before diagnosis. Genetic analysis of the specific APC mutation site may also be considered as mutations between codons 1250 and 1450 more likely have innumerable rectal polyps and a higher risk of developing metachronous rectal cancer.24,32 It must be noted here that in theory, complete removal of all colorectal tissue, ie, proctocolectomy with mucosectomy should eliminate the cancer risk; however, there remains a risk of cancer in the pouch and anal canal, and at the end ileostomy,33 which underscores the need for lifetime surveillance of FAP patients.
Combined-Modality Treatment The multimodality approach in curative intent for an established rectal cancer in the setting of hereditary CRC syndromes does not differ from the one used in sporadic cases. More often, it is more a question of which surgical procedure should be performed now, which procedure has previously been performed, and what is the best time frame for surgery and other treatment modalities. In multiple studies, authors have confirmed that radiation therapy decreased local recurrence rates, and potentially even impact overall survival, though this issue is less clear.34,35 Neoadjuvant chemoradiation has become increasingly the standard for any but the very early rectal cancers. Delivering therapy before surgery appears to have a more substantial effect than postoperative treatment, with significantly improved patient compliance.36 In the setting of a hereditary cancer syndrome, the decision to employ neoadjuvant therapy is generally not different
Multimodality treatment and timing for rectal cancer in HNPCC from sporadic rectal cancer and should have a similar effect of reducing the local recurrence rates. As some of the cancers, particularly high-frequency microsatellite instability cancers in HNPCC, have a decreased response to chemotherapy, the overall effectiveness of the multimodality treatment will have to be further investigated. The one important exception to be remembered is in rectal cancer patients who are planned to receive an ileal pouch. These patients must receive radiotherapy in the neoadjuvant setting because it will no longer be possible postoperatively because of the high rate of pouch failure.37 The detrimental impact of radiation on to the pouch function should mandate an extra effort on the part of the clinician to verify that there is or is not a rectal cancer before operative planning if any consideration is given to a pouch-forming procedure. To remain in compliance with National Cancer Institute recommendations for adjuvant/neoadjuvant treatment of rectal cancers, any preoperatively documented rectal cancer should be rerouted to preoperative treatment. Even the seemingly early rectal cancers are not an exception as the preoperative staging in a rectum with multiple polyps is enormously difficult and unreliable. A dilemma might occur in patients in whom preoperative testing failed to reveal a rectal cancer, but either intraoperative findings or examination of the resected specimen shows a malignancy. There have not been any clear guidelines, and the unfortunate situation should be individualized. Depending on the tumor size and presumed stage and location, one has to decide whether ● ●
●
to abort the procedure before beginning the resection to allow for neoadjuvant radiation; to do the resection but to either create a permanent ileostomy or to defer creation of a pelvic pouch to allow for postoperative radiation, followed by pouch creation; or to create the pouch and forgo radiation treatment (if the tumor appears to be an early stage).
In the latter situation with localized disease on one hand, or in stage IV disease by contrast, one might select chemotherapy only.
Conclusions Management of rectal cancer is complex and dictated by cancer stage and location, the patient’s overall presentation and condition, and the presence or absence of an underlying disease. Functional aspects and goals are much more important than in treatment for colon cancer. Neoadjuvant treatment has evolved as the most common approach for stage II and III cancer. Rectal cancer in the setting of a hereditary cancer syndrome (HNPCC, FAP) is not genuinely handled with a different approach, except that rectal cancer in light of a planned IPAA should always be treated with a neo-adjuvant modality.
139
References 1. Colon and Rectal Cancer. 2010. National Cancer Institute At: http:// www.cancer.gov. Accessed: November 23, 2010 2. Julien LA, Thorson AG: Current neoadjuvant strategies in rectal cancer. J Surg Oncol 101:321-326, 2010 3. Castells A, Castellvi-Bel S, Balaguer F: Concepts in familial colorectal cancer: where do we stand and what is the future? Gastroenterology 137:404-409, 2009 4. Gryfe R: Inherited colorectal cancer syndromes. Clin Colon Rect Surg 22:198-208, 2009 5. Lee JS, Petrelli NJ, Rodriguez-Bigas MA: Rectal cancer in hereditary nonpolyposis colorectal cancer. Am J Surg 181:207-210, 2001 6. Evans DG, Walsh S, Jeacock J, et al: Incidence of hereditary nonpolyposis colorectal cancer in a population-based study of 1137 consecutive cases of colorectal cancer. Br J Surg 84:1281-1285, 1997 7. Cunningham D, Atkin W, Lenz HJ, et al: Colorectal cancer. Lancet 375:1030-1047, 2010 8. Hampel H, Stephens JA, Pukkala E, et al: Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology 129:415-421, 2005 9. Winawer S, Fletcher R, Rex D, et al: Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence. Gastroenterology 124:544-560, 2003 10. de Vos tot Nederveen Cappel WH, Nagengast FM, Griffioen G, et al: Surveillance for hereditary nonpolyposis colorectal cancer: a long-term study on 114 families. Dis Colon Rectum 45:1588-1594, 2002 11. Fitzgibbons RJ Jr, Lynch HT, Stanislav GV, et al: Recognition and treatment of patients with hereditary nonpolyposis colon cancer (Lynch syndromes I and II). Ann Surg 206:289-295, 1987 12. Möslein G, Nelson H, Thibodeau S, et al: Rectal carcinomas in HNPCC [in German]. Langenbecks Arch Chir Suppl Kongressbd 115:14671469, 1998 13. Pollack J, Holm T, Cedermark B, et al: Long-term effect of preoperative radiation therapy on anorectal function. Dis Colon Rectum 49:345352, 2006 14. Kinzler KW, Nilbert MC, Su LK, et al: Identification of FAP locus genes from chromosome 5q21. Science 253:661-665, 1991 15. Nishisho I, Nakamura Y, Miyoshi Y, et al: Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 253:665669, 1991 16. Vasen HF, Moslein G, Alonso A, et al: Guidelines for the clinical management of familial adenomatous polyposis (FAP). Gut 57:704-713, 2008 17. Lockhart-Mummery JP: The causation and treatment of multiple adenomatosis of the colon. Ann Surg 99:178-184, 1934 18. Aziz O, Athanasiou T, Fazio VW, et al: Meta-analysis of observational studies of ileorectal versus ileal pouch-anal anastomosis for familial adenomatous polyposis. Br J Surg 93:407-417, 2006 19. Andrews L, Mireskandari S, Jessen J, et al: Impact of familial adenomatous polyposis on young adults: quality of life outcomes. Dis Colon Rectum 50:1306-1315, 2007 20. Bess MA, Adson MA, Elveback LR, et al: Rectal cancer following colectomy for polyposis. Arch Surg 115:460-467, 1980 21. Heiskanen I, Jarvinen HJ: Fate of the rectal stump after colectomy and ileorectal anastomosis for familial adenomatous polyposis. Int J Colorectal Dis 12:9-13, 1997 22. De Cosse JJ, Bulow S, Neale K, et al: Rectal cancer risk in patients treated for familial adenomatous polyposis. The Leeds Castle Polyposis Group. Br J Surg 79:1372-1375, 1992 23. Tonelli F, Valanzano R, Monaci I, et al: Restorative proctocolectomy or rectum-preserving surgery in patients with familial adenomatous polyposis: results of a prospective study. World J Surg 21:653-658, 1997; discussion: 9 24. Sinha A, Tekkis PP, Rashid S, et al: Risk factors for secondary proctectomy in patients with familial adenomatous polyposis. Br J Surg 97: 1710-1715, 2010 25. Bertario L, Russo A, Radice P, et al: Genotype and phenotype factors as determinants for rectal stump cancer in patients with familial adeno-
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26.
27. 28.
29.
30.
31.
matous polyposis. Hereditary Colorectal Tumors Registry. Ann Surg 231:538-543, 2000 Slors JF, den Hartog-Jager FC, Trum JW, et al: Long-term follow-up after colectomy and ileorectal anastomosis in familial adenomatous polyposis coli. Is there still a place for the procedure? Hepato Gastroenterol 36:109-112, 1989 Jang YS, Steinhagen RM, Heimann TM: Colorectal cancer in familial adenomatous polyposis. Dis Colon Rectum 40:312-316, 1997 Mills SJ, Chapman PD, Burn J, et al: Endoscopic screening and surgery for familial adenomatous polyposis: dangerous delays. Br J Surg 84:7477, 1997 Iwama T, Mishima Y, Utsunomiya J: The impact of familial adenomatous polyposis on the tumorigenesis and mortality at the several organs. Its rational treatment. Ann Surg 217:101-108, 1993 Tonelli F, Valanzano R: Rectal Polyps after ileorectal anastomosis: what is the future? in Delaini GG, ST, Colucci G (eds): Intestinal Polyps and Polyposis Italia, Springer-Verlag, 2009, pp 185-189 Vasen HF, van Duijvendijk P, Buskens E, et al: Decision analysis in the surgical treatment of patients with familial adenomatous polyposis: a
32.
33. 34.
35.
36.
37.
Dutch-Scandinavian collaborative study including 659 patients. Gut 49:231-235, 2001 Nieuwenhuis MH, Bulow S, Bjork J, et al: Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery. Dis Colon Rectum 52:1259-1263, 2009 Church J: Ileoanal pouch neoplasia in familial adenomatous polyposis: an underestimated threat. Dis Colon Rectum 48:1708-1713, 2005 Swedish Rectal Cancer Trial: Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med 336:980-987, 1997 Kapiteijn E, Marijnen CA, Nagtegaal ID, et al: Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med 345:638-646, 2001 Sauer R, Becker H, Hohenberger W, et al: Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:17311740, 2004 Radice E, Nelson H, Devine RM, et al: Ileal pouch-anal anastomosis in patients with colorectal cancer: long-term functional and oncologic outcomes. Dis Colon Rectum 41:11-17, 1998
R
ectal cancer is a significant cause of morbidity and mortality in the United States, with more than 39,600 new cases expected this year, and just more than 51,000 deaths from both colon and rectal cancer combined.1 Overall, rectal adenocarcinoma accounts for nearly 30% of all colorectal cancer (CRC).2 Treatment of rectal cancer is complex and differs from colon cancer in that there is significant interplay of the varying therapeutic modalities. Timing of chemotherapy, radiotherapy, and surgery depend on the overall clinical scenario. In addition, the type of surgery planned is governed by several factors, mainly the oncological outcome, along with quality of life aspects, such as sphincter preservation. Although most CRC cases are of sporadic origin, an estimated 20% of patients have some type of familial inheritance of their disease, and approximately 5% experience a welldefined hereditary syndrome,3 for example, hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), MYH-associated polyposis, or the hamartomatous polyposis syndromes.4 HNPCC and FAP are the most common of these syndromes and represent 2 fairly distinct clinical scenarios that might alter the typical paradigms of rectal cancer treatment. The goal of this review is to discuss
Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD. Address reprint requests to: Jonathan E. Efron, MD, FACS, FASCRS, Department of Surgery, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 656, Baltimore, MD 21287. E-mail: [email protected]
1043-1489/$-see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1053/j.scrs.2010.12.016
the nuances of treating rectal cancer that arises in the background of hereditary CRC, with a focus on HNPCC and FAP.
Hereditary Nonpolyposis Colorectal Cancer HNPCC is the most common of the inherited CRC syndromes, accounting for between 2% and 5% of all cases of CRC.5,6 It is autosomal dominant with a mutation in the DNA mismatch-repair gene system (almost two-thirds of cases are caused by a mutation in either MSH2 or MLH1) that is associated with microsatellite instability.7 In this setting, on average, presents approximately 20 years earlier than sporadic CRC,7 although newer data suggest that the average age at the time of diagnosis may be closer to 60.8 In comparison with FAP, HNPCC can present a more complex diagnostic quandary: there is typically no readily apparent polyposis, and the overall lifetime risk of developing CRC is at least 50%-60%.4 Diagnostic tools for HNPCC are the Amsterdam II criteria and the Revised Bethesda Guidelines as impetus to perform genetic testing.4 Patients with suspected or confirmed HNPCC should be screened with colonoscopy from their mid20s with at least yearly examinations,9 as the polyp-to-cancer transformation is significantly accelerated.10 CRC in HNPCC are “right-sided” (proximal to the splenic flexure) 70% of the time.4,11 However, a couple of retrospective studies have demonstrated that a rectal carcinoma may be the actual index or primary lesion in 21%-29% of HNPCC cases.5,12 The 3 factors that impact the choices for treatment 137
A.N. Demirjian and J.E. Efron
138 are (a) the location and stage of the primary tumor(s), (b) the risk for metachronous lesions, and (c) the functional aspects. In the setting of HNPCC, risk-reducing surgery is an attractive option as long as the rectum can be preserved, ie, for cases with colon cancer. As in cases of sporadic rectal cancer, surgical treatment options for rectal index lesions in HNPCC include on rare occasions a local excision, and most commonly an oncological resection (low-anterior resection, abdominoperineal resection, proctocolectomy with ileal pouch anal anastomosis [IPAA], or an end ileostomy). One of the key questions is the incidence of metachronous lesions in patients with a rectal cancer as their primary lesion. The authors of 2 retrospective studies demonstrated a very disparate incidence of a second colon cancer. In a study from the Roswell Park Cancer Institute in Buffalo, the incidence was 17% after a mean interval of 201 months.5 In contrast Möslein et al12 from Germany reported a much higher number of 54%, after a mean latency period of 7.4 years. It is difficult to determine the reason for these differences, but one should caution that both studies were retrospective and entailed only small groups of patients from 1 institution. The question of the true risk of metachronous lesions and which of the 2 reports more accurately reflects the incidence is critical: ●
●
If the 17% incidence is accurate, it may be prudent to treat HNPCC patients the same as sporadic rectal cancer patients. This would most commonly involve stage-dependent neoadjuvant chemoradiation, followed by an oncological resection. It is important to note that neoadjuvant radiation has been associated with a negative impact on the sphincter function, which is particularly important in cases where the baseline tone is diminished.13 If the number, however, is closer to one-half of all patients, the first approach with colonoscopic surveillance remains an option, but the alternative of a prophylactic procedure beyond the curative resection should be discussed with the patient. The later would involve a proctocolectomy with IPAA or an end ileostomy. Undoubtedly, the bowel frequency and function after an IPAA would differ significantly from normal or a low-anterior resection or colo-anal anastomosis. The cancer risk needs to be weighed against the patient’s quality of life.
Familial Adenomatous Polyposis FAP results from an autosomal-dominant germline mutation in the APC gene. It is characterized by the development of multiple adenomatous polyps beginning from the second life decade14,15 and a near 100% progression to CRC by the fourth or fifth decade of life if untreated.16 However, it only accounts for ⬍1% of all CRC.4 Surgical resection in prophylactic or therapeutic intent has evolved as the most important concept for this disease since the 1930s.17 It is not clear from the literature how often rectal cancers present as the index lesion. Much more attention has been paid to the concern
developing rectal cancer following prophylactic surgery. For the decision between ileo-rectal anastomosis and IPAA, 2 aspects have to be balanced: ●
●
obtaining a satisfactory oncological (or more accurately prophylactic) outcome, including the need for surveillance and potential subsequent surgeries; and achieving an acceptable functional result.
Preserving the rectum through the use of ileo-rectal anastomosis might create a better functional outcome for patients as measured by lower numbers of total daily bowel motions, a decreased need to use absorbent undergarment pads, and less frequent nighttime accidents18; increased confidence in one’s body image; or increase in sexual function.19 The flip side of rectal preservation is the subsequent risk of developing a rectal cancer, which overall has to be considered significant with a range from 5% at 5 years up to 59% after 23 years,20,21 even if lower numbers were reported by others.22 The factors that correlate best with increased risk are the number of rectal polyps greater than 10-20,23,24 patient age, polyp size ⬎1 cm, length of the rectal stump, the presence of cancer in the original colonic specimen, and the compliance with stump surveillance.24-29 Although endoscopic surveillance is perceived as being safe and effective,24,30 investigators from a larger population-based study from northern Europe questioned it adequacy. Vasen et al31 reported that 75% of patients who eventually developed rectal cancer had an endoscopy within 12 months before diagnosis. Genetic analysis of the specific APC mutation site may also be considered as mutations between codons 1250 and 1450 more likely have innumerable rectal polyps and a higher risk of developing metachronous rectal cancer.24,32 It must be noted here that in theory, complete removal of all colorectal tissue, ie, proctocolectomy with mucosectomy should eliminate the cancer risk; however, there remains a risk of cancer in the pouch and anal canal, and at the end ileostomy,33 which underscores the need for lifetime surveillance of FAP patients.
Combined-Modality Treatment The multimodality approach in curative intent for an established rectal cancer in the setting of hereditary CRC syndromes does not differ from the one used in sporadic cases. More often, it is more a question of which surgical procedure should be performed now, which procedure has previously been performed, and what is the best time frame for surgery and other treatment modalities. In multiple studies, authors have confirmed that radiation therapy decreased local recurrence rates, and potentially even impact overall survival, though this issue is less clear.34,35 Neoadjuvant chemoradiation has become increasingly the standard for any but the very early rectal cancers. Delivering therapy before surgery appears to have a more substantial effect than postoperative treatment, with significantly improved patient compliance.36 In the setting of a hereditary cancer syndrome, the decision to employ neoadjuvant therapy is generally not different
Multimodality treatment and timing for rectal cancer in HNPCC from sporadic rectal cancer and should have a similar effect of reducing the local recurrence rates. As some of the cancers, particularly high-frequency microsatellite instability cancers in HNPCC, have a decreased response to chemotherapy, the overall effectiveness of the multimodality treatment will have to be further investigated. The one important exception to be remembered is in rectal cancer patients who are planned to receive an ileal pouch. These patients must receive radiotherapy in the neoadjuvant setting because it will no longer be possible postoperatively because of the high rate of pouch failure.37 The detrimental impact of radiation on to the pouch function should mandate an extra effort on the part of the clinician to verify that there is or is not a rectal cancer before operative planning if any consideration is given to a pouch-forming procedure. To remain in compliance with National Cancer Institute recommendations for adjuvant/neoadjuvant treatment of rectal cancers, any preoperatively documented rectal cancer should be rerouted to preoperative treatment. Even the seemingly early rectal cancers are not an exception as the preoperative staging in a rectum with multiple polyps is enormously difficult and unreliable. A dilemma might occur in patients in whom preoperative testing failed to reveal a rectal cancer, but either intraoperative findings or examination of the resected specimen shows a malignancy. There have not been any clear guidelines, and the unfortunate situation should be individualized. Depending on the tumor size and presumed stage and location, one has to decide whether ● ●
●
to abort the procedure before beginning the resection to allow for neoadjuvant radiation; to do the resection but to either create a permanent ileostomy or to defer creation of a pelvic pouch to allow for postoperative radiation, followed by pouch creation; or to create the pouch and forgo radiation treatment (if the tumor appears to be an early stage).
In the latter situation with localized disease on one hand, or in stage IV disease by contrast, one might select chemotherapy only.
Conclusions Management of rectal cancer is complex and dictated by cancer stage and location, the patient’s overall presentation and condition, and the presence or absence of an underlying disease. Functional aspects and goals are much more important than in treatment for colon cancer. Neoadjuvant treatment has evolved as the most common approach for stage II and III cancer. Rectal cancer in the setting of a hereditary cancer syndrome (HNPCC, FAP) is not genuinely handled with a different approach, except that rectal cancer in light of a planned IPAA should always be treated with a neo-adjuvant modality.
139
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