Technik der mesorektaler Exzision beim Rektumkarzinom - immer noch ein aktuelles Thema?

Zusammenfassung

Innerhalb der letzten zehn Jahre wurden erhebliche Fortschritte in der Behandlung des Rektumkarzinoms erzielt. Heutzutage werden Adenokarzinome des Rektums auf der Basis eines umfassenden interdisziplinären Stagings UICC-Stadien-abhängig therapiert. Die notwendigen Staginguntersuchungen umfassen die starre Rektoskopie (mit Tumorbiopsie), die rektale Endosonographie, die Kontrastmittel-gestützte Computertomographie und/oder Magnetresonanz-Tomographie der Beckenregion: UICC-I Karzinome können allein durch die Operation geheilt werden, sofern die Prinzipien einer qualitätsgesicherten, onkologischen Resektion unter Anwendung der „No-touch”-Technik, der radikulären Gefäßabsetzung und der totalen mesorektalen Exzision eingehalten werden. Demgegenüber erhalten im unteren und mittleren Rektumdrittel lokalisierte UICC-II/III-Karzinome (T3/T4 o. N+) präoperativ eine Radiochemotherapie (RT/CT) mit 5-FU als Radiosensitizer gemäß den Ergebnissen der CAO/AIO/ARO-94 Studie der German Rectal Cancer Study Group (GRCSG). Für Karzinome im oberen Rektumdrittel (12-16 cm oberhalb der Anokutanlinie) ist die Effektivität der präoperativen RT/CT und TME jedoch umstritten. Die partielle Mesorektumexzision (PME) scheint bei diesen Karzinomen der TME überlegen zu sein, vorausgesetzt ein 4 cm bis 5 cm breiter Sicherheitsabstand kann eingehalten und ein Coning des mesorektalen Gewebes vermieden werden. Zudem gibt es Hinweise, dass Karzinome des oberen Rektumdrittels wie Sigmakarzinome behandelt werden sollten. Vor diesem Hintergrund sind zwei multizentrische Studien aktiviert worden: Die CAO/AIO/ARO-04 Phase-III-Studie der GRCSG prüft die Effektivität einer intensivierten präoperativen RT/CT (5-FU und Oxaliplatin als Radiosensitizer) und adjuvanten Chemotherapie bei UICC-II/III-Rektumkarzinomen der unteren zwei Rektumdrittel gegenüber der allein 5-FU-basierten RT/CT. Die German Advanced Surgical Study Group (GAST) untersucht in ihrer randomisierten Phase-II-Studie den chirurgischen Behandlungserfolg einer qualitätsüberprüften PME gegenüber einer TME bei Karzinomen des oberen Rektumdrittels. Postoperativ erhalten alle Patienten eine adjuvante Standardchemotherapie. Die GAST-05-Studie soll letztlich klären, ob Karzinome des oberen Rektumdrittels als Rektum- oder als Kolonkarzinome klassifiziert und dem entsprechend therapiert werden müssen.

Abstract

During the last decade, considerable progress has been made in the treatment of rectal cancer. Based on improved interdisciplinary staging procedures, rectal cancers today are treated according to their UICC stage. The staging procedures include rigid rectoscopy, rectal ultrasound, computed tomography and/or magnetic resonance tomography of the pelvic region. Carcinomas at UICC stage I can be cured by surgery alone if high-quality resection procedures are applied that are based on radical oncologic principles such as the “no touch” technique, radicular dissection of vessels, and total mesorectal excision (TME). Locally advanced rectal cancers at UICC stages II/III (T3/T4 or N+) that are localized at the lower and middle third of the rectum should receive additional neoadjuvant 5-FU-based chemoradiotherapy (RT/CT) followed by TME, according to the results of the CAO/AIO/ARO-94 trial of the German Rectal Cancer Study Group (GRCSG). For rectal cancer of the upper third of the rectum (12-16 cm above anocutaneous verge) both the efficacy of preoperative RT/CT and TME are still under discussion. Here, partial mesorectal excision (PME) for proximal cancer appears to be superior to TME, provided that a 4 to 5 cm mesorectal margin can be achieved without coning of the tissue. Furthermore, there is evidence that rectal cancer of the upper third should be treated the same way as sigmoid cancer. Two multicentric studies are being carried out that seem to confirm this assumption: The CAO/AIO/ARO-04 phase III trial of the GRCSG is investigating the efficacy of an intensified preoperative RT/CT (5-FU and oxaliplatin) and adjuvant chemotherapy in UICC stage II/III rectal cancers of the lower and middle third of the rectum compared to 5-FU monotherapy-based RT/CT. The German Advanced Surgical Study Group (GAST) is investigating the therapy of rectal cancers of the upper third of the rectum. This randomized phase II trial compares PME- with TME-treatment of UICC stage II/III cancer prior to adjuvant therapy. The study is designed to answer the question whether cancers of the upper third of the rectum should be classified and treated as rectal cancers or rather as colonic cancers.

Schlüsselwörter

Totale und partielle mesorektale Exzision - Rektumkarzinom - CAO/AIO/ARO-94-Studie - GAST-05-Studie

Key words

total and partial mesorectal excision - rectal cancer - CAO/AIO/ARO-94 study - GAST-05 study

Literatur

• 1 Andre T, Boni C, Mounedji-Boudiaf L. et al . Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer.  N Engl J Med. 2004;  350 2343-2351
• 2 Arbeitgemeinschaft Bevölkerungsbezogener Krebsregister in Deutschland in Zusammenarbeit mit dem Robert Koch Institut .Krebs in Deutschland. Häufigkeiten und Trends. ISBN 3-88718-153-0. www.rki.de/gbe/krebs/broschuere2002/broschuere2002.htm. 3. Ausgabe. Saarbrücken 2002
• 3 Becker H, Liersch T. Rektumkarzinom. In: Viszeralchirurgie. [Becker H, Encke A, Röher HD] (Hrsg). 2. Auflage. Elsevier GmbH, Urban & Fischer, München 2006; 602-631
• 4 Cedermark B, Johansson H, Rutqvist L E, Wilking N. Stockholm Colorectal Cancer Study Group . The Stockholm I trial of preoperative short term radiotherapy in operable rectal carcinoma. A prospective randomized trial.  Cancer. 1995;  75 2269-2275
• 5 Crane C H, Skibber J M, Feig B W. et al . Response to preoperative chemoradiation increases the use of sphincter-preserving surgery in patients with locally advanced low rectal carcinoma.  Cancer. 2003;  97 517-524
• 6 Dunst J, Reese T, Frings S. et al . Phase I trial evaluating the concurrent combination of radiotherapy and capecitabine in rectal cancer.  J Clin Oncol. 2002;  20 3983-3991
• 7 Dworak O, Keilholz L, Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy.  Int J Colorectal Dis. 1997;  12 19-23
• 8 Enker W E, Thaler H T, Cranor M L. et al . Total mesorectal excision in the operative treatment of carcinoma of the rectum.  J Am Coll Surg. 1995;  181 335-346
• 9 Ferlay J, Bray F, Pisani P. et al .GLOBOCAN 2002. Cancer Incidence, Mortality and Prevalence Worldwide. IARC CancerBase No. 5. Version 2.0. IARC press, Lyon, France 2004 www-depdb.iarc.fr/globocan/GLOBOframe.htm
• 10 Folkesson J, Birgisson H, Pahlmann L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial . Long lasting benefits from radiotherapy on survival and local recurrence rate.  J Clin Oncol. 2005;  23 5644-5650
• 11 Francois Y, Nemoz C J, Baulieux J. et al . Influence of the interval between preoperative radiation therapy and surgery on downstaging and on the rate of sphincter-sparing surgery for rectal cancer. The Lyon R90-01 randomized trial.  J Clin Oncol. 1999;  17 2396-2402
• 12 Frykholm G J, Glimelius B, Pahlman L. Preoperative or postoperative irradiation in adenocarcinoma of the rectum. Final treatment results of a randomized trial and an evaluation of late secondary effects.  Dis Colon Rectum. 1993;  36 564-572
• 13 Frykholm G J, Pahlman L, Glimelius B. Combined chemo- and radiotherapy vs. radiotherapy alone in the treatment of primary, nonresectable adenocarcinoma of the rectum.  Int J Radiat Oncol Biol Phys. 2001;  50 427-434
• 14 Gerard A, Buyse M, Nordinger B. et al . Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomised study of the European Organisation for Research and Treatment of Cancer (EORTC).  Ann Surg. 1988;  208 606-614
• 15 Gerard J P, Chapet O, Nemoz C. et al . Preoperative concurrent chemoradiotherapy in locally advanced rectal cancer with high-dose radiation and oxaliplatin-containing regimen. The Lyon R0-04 phase II trial.  J Clin Oncol. 2003;  21 1119-1124
• 16 Ghadimi B M, Grade M, Difilippantonio M J. et al . Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy.  J Clin Oncol. 2005;  23 1826-1838
• 17 Gunderson L L, Sargent D J, Tepper J E. et al . Impact of T and N substage on survival and disease relapse in adjuvant rectal cancer. A pooled analysis.  Int J Radiat Oncol Biol Phys. 2002;  54 386-396
• 18 Heald R J, Moran B J, Ryall R D. et al . Rectal cancer. The Basingstoke experience of total mesorectal excision, 1978-1997.  Arch Surg. 1998;  133 894-899
• 19 Heald R J, Ryall R D. Recurrence and survival after total mesorectal excision for rectal cancer.  Lancet. 1986;  1 1479-1482
• 20 Heald R J, Ryall R DH, Husband E. The mesorectum in rectal cancer surgery. Clue to pelvic recurrence.  Br J Surg. 1982;  69 613-616
• 21 Hermanek P, Heald R J. Pre-operative radiotherapy for rectal carcinoma? Has the case really been made for short course pre-operative radiotherapy if surgical standards for rectal carcinoma are optimal?.  Colorectal Disease. 2003;  6 10-14
• 22 Hermanek P, Hermanek P, Hohenberger W. et al . The pathological assessment of mesorectal excision. Implications for further treatment quality management.  Int J Colorectal Dis. 2003;  18 335-341
• 23 Hermanek P. Impact of surgeon's technique on outcome after treatment of rectal carcinoma.  Dis Colon Rectum. 1999;  42 559-562
• 24 Hida J, Yasutomi M, Maruyama T. et al . Lymph node metastases detected in the mesorectum distal to carcinoma of the rectum by the clearing method. Justification of total mesorectal excision.  J Am Coll Surg. 1997;  184 584-588
• 25 Hofheinz R D, Gerstenberg-Helldorf B von, Wenz F. et al . Phase I trial of capecitabine and weekly irinotecan in combination with radiotherapy for neoadjuvant therapy of rectal cancer.  J Clin Oncol. 2005;  23 1350
• 26 Holm T, Johansson H, Rutqvist L E, Cedermark B. Tumour location and the effects of preoperative radiotherapy in the treatment of rectal cancer.  Br J Surg. 2001;  88 839-843
• 27 Jemal A, Tiwari R C, Murray T. et al . Cancer Statistics, 2004.  CA Cancer J Clin. 2004;  54 8-29
• 28 Johnston P G. Prognostic markers of local relapse in rectal cancer. Are we any further forward?.  J Clin Oncol. 2006;  24 4049-4050
• 29 Kapiteijn E, Marijnen C A, Nagtegaal I D. et al . Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.  N Engl J Med. 2001;  345 638-646
• 30 Kapiteijn E, Putter H, van de Velde C J. et al . Impact of the introduction and training of total mesorectal excision on recurrence and survival in rectal cancer in the Netherlands.  Br J Surg. 2002;  89 1142-1149
• 31 Law W L, Chu K W. Anterior resection for rectal cancer with mesorectal excision. A prospective evaluation of 622 patients.  Ann Surg. 2004;  240 260-268
• 32 Leong A F. Selective total mesorectal excision for rectal cancer.  Dis Colon Rectum. 2000;  43 1237-1240
• 33 Liersch T, Langer C, Ghadimi B M, Kulle B, Aust D E, Baretton G B, Schwabe W, Häusler P, Becker H, Jakob C. Lymph node status and TS gene expression are prognostic markers in locally advanced rectal cancer after neoadjuvant Fluorouracil-based chemoradiotherapy.  J Clin Oncol. 2006;  24 4062-4068
• 34 Liersch T, Langer C, Jakob C. et al . Preoperative diagnostic procedures in locally advanced rectal carcinoma (> or = T3 or N +). What does endoluminal ultrasound achieve at staging and restaging (after neoadjuvant radiochemotherapy) in contrast to computed tomography?.  Chirurg. 2003;  74 224-234
• 35 Lopez-Kostner F, Lavery I C, Hool G R, Rybicki L A, Fazio V W. Total mesorectal excision is not necessary for cancers of the upper rectum.  Surgery. 1998;  124 612-618
• 36 M.E.R.C.U.R.Y. Project (Magnetic Resonance Imaging and Rectal Cancer European Equivalence Study) .Study Protocol. Study Coordinator I. Daniels, FRCS, Pelican Centre, North Hampshire Hospital, Basingstoke, Hampshire, UK). www.pelicancancer.org/researchprojects 2002
• 37 Marijnen C A, van de Velde C J, Putter H, van den Brinck M, Maas C P, Martijn H, Rutten H J, Wiggers T, Kranenbarg E K, Leer J W, Stiggelbout A M. Impact of short-term preoperative radiotherapy on health-related quality of life and sexual functioning in primary rectal cancer. Report of a multicenter randomized trial.  J Clin Oncol. 2005;  23 1847-1858
• 38 Martling A, Holm T, Johansson H, Rutquist L E, Cedermark B. The Stockholm II trial on preoperative radiotherapy in rectal carcinoma. Long-term follow-up of a Population-based study.  Cancer. 2001;  92 896-902
• 39 Martling A, Holm T, Rutquist L E, Johansson H, Moran B J, Heald R J, Cedermark B. Impact of a surgical training programme on rectal cancer outcomes in Stockholm.  Br J Surg. 2005;  92 225-229
• 40 Martling A L, Holm T, Rutquist L E, Moran B J, Heald R J, Cedermark B. Stockholm Colorectal Cancer Study Group, Basingstoke Bowel Cancer Research Project . Effect of a surgical training programme on outcome of rectal cancer in the County of Stockholm.  Lancet. 2000;  356 93-96
• 41 Medical Research Council Rectal Cancer Working Party . Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer.  Lancet. 1996;  348 1605-1610
• 42 Nagtegaal I D, van de Velde C J, van der Worp E, Kapiteijn E, Quirke P, van Krieken J H. Macroscopic evaluation of rectal cancer resection specimen. Clinical significance of the pathologist in quality control.  J Clin Oncol. 2002;  20 1729-1734
• 43 Nagtegaal I D, van de Velde C J, Marijnen C A, van Krieken J H, Quirke P. Low rectal cancer: A call for a change of approach in abdominoperineal resection.  J Clin Oncol. 2005;  23 9257-9264
• 44 Nissan A, Stojadinovic A, Shia J, Hoos A, Guillem J G, Klimstra D, Cohen A M, Minsky B D, Paty P B, Wong W D. Predictors of recurrence in patients with T2 and early T3, N0 adenocarcinoma of the rectum treated by surgery alone.  J Clin Oncol. 2006;  24 4078-4084
• 45 Porter G A, Soskolne C L, Yakimets W W, Newman S C. Surgeon-related factors and outcome in rectal cancer.  Ann Surg. 1998;  227 157-167
• 46 Ptok H, Steinert R, Meyer F, Kröll K P, Scheele C, Köckerling F, Gastinger I, Lippert H. Operative Behandlung von Rektumkarzinomen im Vergleich. Onkologische Langzeitergebnisse einer multizentrischen Beobachtungsstudie nach laparoskopisch-assistierter, konvertierter und primär offener Operation.  Chirurg. 2006;  77 709-717
• 47 Quirke P. The pathologist, the surgeon and colorectal cancer get it right because it matters.  Prog Pathol. 1998;  4 201-213
• 48 Quirke P. Training and quality assurance for rectal cancer. 20 years of data is enough.  Lancet Oncol. 2003;  4 695-702
• 49 Quirke P, Durdey P, Dixon M. et al . Local recurrence of rectal adenocarcinoma due to inadequate surgical resection. Histopathological study of lateral tumor spread and surgical excision.  Lancet. 1986;  2 996-999
• 50 Reynolds J V, Joyce W P, Dolan J, Sheahan K, Hyland J M. Pathological evidence in support of total mesorectal excision in the management of rectal cancer.  Br J Surg. 1996;  83 1112-1115
• 51 Rödel C, Grabenbauer G G, Papadopoulos T, Hohenberger W, Schmoll H J, Sauer R. Phase I/II trial of capecitabine, oxaliplatin, and radiation for rectal cancer.  J Clin Oncol. 2003;  21 3098-3104
• 52 Rödel C, Grabenbauer G G, Schick C. et al . Preoperative radiation with concurrent 5-fluorouracil for locally advanced T4-primary rectal cancer.  Strahlenther Onkol. 2000;  176 161-167
• 53 Rödel C, Liersch T, Hermann R M. et al . Multicenter phase II trial of the German Rectal Cancer Study Group. Preoperative radiation with concomitant and adjuvant capecitabine and oxaliplatin for rectal cancer.  J Clin Oncol. 2006;  , , in press
• 54 Rödel C, Martus P, Papadoupolos T. et al . Prognostic significance of tumor regression grading following preoperative chemoradiotherapy for rectal cancer.  J Clin Oncol. 2005;  23 8688-8696
• 55 Sauer R, Becker H, Hohenberger W. et al . Preoperative versus postoperative chemoradiotherapy for rectal cancer.  N Engl J Med. 2004;  351 1731-1740
• 56 Schmiegel W, Adler G, Frühmorgen P. et al . Kolorektales Karzinom. Prävention und Früherkennung in der asymptomatischen Bevölkerung - Vorsorge bei Risikopatienten - Endoskopische Diagnostik. Therapie und Nachsorge von Polypen und Karzinomen.  Z Gastroenterol. 2000;  38 49-75
• 57 Schmiegel W, Pox C, Adler G. et al . S3-Leitlinienkonferenz „Kolorektales Karzinom” 2004.  Z Gastroenterol. 2004;  42 1129-1177
• 58 Scott N, Jackson P, Al-Jaberi T. et al . Total mesorectal excision and local recurrence. A study of tumor spread in the mesorectum distal to rectal cancer.  Br J Surg. 1995;  82 1031-1033
• 59 Sobin L H, Wittekind C. TNM classification of malignant tumors. Springer, Berlin, Heidelberg, New York 2002
• 60 Soreide O, Norstein J, Fielding L P, Silen W. International standardization and documentation of the treatment of rectal cancer. In: Soreide O, Norstein J (eds). Rectal cancer surgery. Optimisation - standardisation - documentation. Springer, Berlin, Heidelberg, New York 1997; 405-445
• 61 Steele Jr  G, Ravikumar T S. Resection of hepatic metastases from colorectal cancer. Biologic perspective.  Ann Surg. 1989;  210 127-138
• 62 Sterk P, Kasperk R, Opitz T, Schubert F, Klein P. Vascular organization in the mesorectum. Angiography of rectal resection specimens.  Int J Colorectal Dis. 2000;  15 225-228
• 63 Swedish Rectal Cancer Trial . Improved survival with preoperative radiotherapy in resectable rectal cancer.  N Engl J Med. 1997;  336 980-987
• 64 Swedish Rectal Cancer Trial . Local recurrence rate in a randomised multicentre trial of preoperative radiotherapy compared with operation alone in respectable rectal carcinoma.  Eur J Surg. 1996;  162 397-402
• 65 Syk E, Torkzad M R, Blomquist L, Ljungqvist O, Glimelius B. Radiological findings do not support lateral residual tumour as a major cause of local recurrence of rectal cancer.  Br J Surg. 2006;  93 113-119 506-507 ,  (authors reply p 507)
• 66 Van de Velde C H. on behalf of the DCCG .The TME trial after 5 years of follow-up. 2nd Multidisciplinary Colorectal Cancer Congress. Noordwijk, The Netherlands 2004
• 67 Van den Brink M, Stiggelbout A M, van den Hout W B, Kievit J, Kranenbarg E K, Marijnen C A, Nagtegaal I D, Rutten H J, Wiggers T, van de Velde C J. Clinical nature and prognosis of locally recurrent rectal cancer after total mesorectal excision with or without preoperative radiotherapy.  J Clin Oncol. 2004;  22 3958-3964
• 68 Wibe A, Carlsen E, Dahl O, Tveit K M, Weedeon-Fekjaer H, Hestvik U E, Wiig J N. on behalf of The Norwegian Rectal Cancer Group . Nationwide quality assurance of rectal cancer treatment.  Colorectal Disease. 2006;  8 224-229
• 69 Wibe A, Moller B, Norstein J. et al . A national strategic change in treatment policy for rectal cancer - implementation of total mesorectal excision as routine treatment in Norway. A national audit.  Dis Colon Rectum. 2002;  45 857-866
• 70 Zaheer S, Pemberton J H, Farouk R. et al . Surgical treatment of adenocarcinoma of the rectum.  Ann Surg. 1998;  227 800-811