Der Stellenwert der (neo-)adjuvanten Therapie beim Rektumkarzinom

Nach Angaben des Statistischen Bundesamtes (www.gbe-bund.de) stellte das Rektumkarzinom im Jahre 1999 das vierthäufigste Karzinom unter allen Krebsneuerkrankungen bei Männern und das dritthäufigste bei Frauen dar; 22662 Bundesbürger erkrankten daran (6,6 % aller Krebsneuerkrankungen). Die Mortalitätsrate lag 1999 bei 7,9/100000 Einwohner, sank jedoch zwischen 1990 und 1999 um 15 % relativ (9,3 % vs. 7,9 %/100 000 Einwohner) (Statistisches Bundesamt).

Dies ist unter anderem auf die Verbesserung chirurgischer Resektionsverfahren mit dem Ziel der kurativen Entfernung des Tumors und Vermeidung von Lokalrezidiven zurückzuführen. Nach Einführung der totalen mesorektalen Exzision (TME) durch Heald [27] [28] konnte die Lokalrezidivrate allein durch die chirurgische Therapie auf unter 10 % reduziert werden [12] [39]. Hermanek et al. berichteten dagegen noch im Jahre 1995 in einer deutschen Multizenterstudie von einer Lokalrezidivrate von 4-55 % mit einem Median von 20 % [29]. Mittlerweile ist die TME als chirurgischer „Goldstandard” beim Rektumkarzinom etabliert.

Die Einführung der TME hat auch die Frage nach dem Stellenwert multimodaler Konzepte in der Therapie des Rektumkarzinoms neu aufgeworfen.

Literatur

• 1 A trial of preoperative radiotherapy in the management of operable rectal cancer.  Br J Surg. 1982;  69 513-519
• 2 The evaluation of low dose pre-operative X-ray therapy in the management of operable rectal cancer: results of a randomly controlled trial.  Br J Surg. 1984;  71 21-25
• 3 Prolongation of the disease-free interval in surgically treated rectal carcinoma: Gastrointestinal Tumor Study Group.  N Engl J Med. 1985;  312 1465-1472
• 4 Stockholm Rectal Cancer Study Group . Preoperative short-term radiation therapy in operable rectal carcinoma. A prospective randomized trial.  Cancer. 1990;  66 49-55
• 5 Swedish Rectal Cancer Trial . Local recurrence rate in a randomised multicentre trial of preoperative radiotherapy compared with operation alone in resectable rectal carcinoma.  Eur J Surg. 1996;  162 397-402
• 6 Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Medical Research Council Rectal Cancer Working Party.  Lancet. 1996;  348 1605-1610
• 7 Stockholm Colorectal Cancer Study Group . Randomized study on preoperative radiotherapy in rectal carcinoma.  Ann Surg Oncol. 1996;  3 423-430
• 8 Swedish Rectal Cancer Trial . Improved survival with preoperative radiotherapy in resectable rectal cancer.  N Engl J Med. 1997;  336 980-987
• 9 Adjuvant radiotherapy for rectal cancer: a systematic overview of 8,507 patients from 22 randomised trials.  Lancet. 2001;  358 1291-1304
• 10 Arnaud J P, Nordlinger B, Bosset J F, Boes G H, Sahmoud T, Schlag P M, Pene F. Radical surgery and postoperative radiotherapy as combined treatment in rectal cancer. Final results of a phase III study of the European Organization for Research and Treatment of Cancer.  Br J Surg. 1997;  84 352-357
• 11 Brown G, Kirkham A, Williams G T, Bourne M, Radcliffe A G, Sayman J, Newell R, Sinnatamby C, Heald R J. High-resolution MRI of the anatomy important in total mesorectal excision of the rectum.  AJR Am J Roentgenol. 2004;  182 431-439
• 12 Buchler M W, Heald R J, Maurer C A, Ulrich B C. Rektumkarzinom: Das Konzept der Totalen Mesorektalen Exzision. Basel, Karger 1998
• 13 Bujko K, Kepka L. In regard to Marijnen et al . Does radiotherapy compensate for a positive resection margin in rectal cancer patients? IJROBP 2003;55:1311 - 1320.  Int J Radiat Oncol Biol Phys. 2003;  57 1199-1200
• 14 Bujko K, Nasierowska-Guttmejer A, Nowacki M P, Wojnar A, Chmielik E, Majewski P, Sygut J, Karmolinski A, Husarski T, Szudrowicz Z, Kepka L. Intramural distal spread of rectal cancer following preoperative radiotherapy: the results of a multicentre randomized clinical study.  Int J Radiat Oncol Biol Phys. 2003;  57 S180
• 15 Dahl O, Horn A, Morild I, Halvorsen J F, Odland G, Reinertsen S, Reisaeter A, Kavli H, Thunold J. Low-dose preoperative radiation postpones recurrences in operable rectal cancer. Results of a randomized multicenter trial in western Norway.  Cancer. 1990;  66 2286-2294
• 16 Dahlberg M, Glimelius B, Pahlman L. Improved survival and reduction in local failure rates after preoperative radiotherapy: evidence for the generalizability of the results of Swedish Rectal Cancer Trial.  Ann Surg. 1999;  229 493-497
• 17 Douglass H O, Moertel C G, Mayer R J, Thomas P R, Lindblad A S, Mittleman A, Stablein D M, Bruckner H W. Survival after postoperative combination treatment of rectal cancer.  N Engl J Med. 1986;  315 1294-1295
• 18 Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham D L, Fisher E R, Caplan R, Jones J, Lerner H. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01.  J Natl Cancer Inst. 1988;  80 21-29
• 19 Francois Y, Nemoz C J, Baulieux J, Vignal J, Grandjean J P, Partensky C, Souquet J C, Adeleine P, Gerard J P. 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
• 20 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
• 21 Frykholm G J, Sintorn K, Montelius A, Jung B, Pahlman L, Glimelius B. Acute lumbosacral plexopathy during and after preoperative radiotherapy of rectal adenocarcinoma.  Radiother Oncol. 1996;  38 121-130
• 22 Gerard A, Berrod J L, Pene F, Loygue J, Laugier A, Bruckner R, Camelot G, Arnaud J P, Metzger U, Buyse M. Interim analysis of a phase III study on preoperative radiation therapy in resectable rectal carcinoma. Trial of the Gastrointestinal Tract Cancer Cooperative Group of the European Organization for Research on Treatment of Cancer (EORTC).  Cancer. 1985;  55 2373-2379
• 23 Gerard A, Buyse M, Nordlinger B, Loygue J, Pene F, Kempf P, Bosset J F, Gignoux M, Arnaud J P, Desaive C. Preoperative radiotherapy as adjuvant treatment in rectal cancer. Final results of a randomized study of the European Organization for Research and Treatment of Cancer (EORTC).  Ann Surg. 1988;  208 606-614
• 24 Glimelius B. Chemoradiotherapy for rectal cancer ( is there an optimal combination?.  Ann Oncol. 2001;  12 1039-1045
• 25 Glimelius B, Pahlman L. Perioperative radiotherapy in rectal cancer.  Acta Oncol. 1999;  38 23-32
• 26 Goldberg P A, Nicholls R J, Porter N H, Love S, Grimsey J E. Long-term results of a randomised trial of short-course low-dose adjuvant pre-operative radiotherapy for rectal cancer: reduction in local treatment failure.  Eur J Cancer. 1994;  30A 1602-1606
• 27 Heald R J, Husband E M, Ryall R D. The mesorectum in rectal cancer surgery ( the clue to pelvic recurrence?.  Br J Surg. 1982;  69 613-616
• 28 Heald R J, Ryall R D. Recurrence and survival after total mesorectal excision for rectal cancer.  Lancet. 1986;  1 1479-1482
• 29 Hermanek P, Wiebelt H, Staimmer D, Riedl S. Prognostic factors of rectum carcinoma ( experience of the German Multicentre Study SGCRC. German Study Group Colo-Rectal Carcinoma.  Tumori. 1995;  81 60-64
• 30 Horn A, Halvorsen J F, Dahl O. Preoperative radiotherapy in operable rectal cancer.  Dis Colon Rectum. 1990;  33 823-828
• 31 Hyams D M, Mamounas E P, Petrelli N, Rockette H, Jones J, Wieand H S, Deutsch M, Wickerham L, Fisher B, Wolmark N. A clinical trial to evaluate the worth of preoperative multimodality therapy in patients with operable carcinoma of the rectum: a progress report of National Surgical Breast and Bowel Project Protocol R-03.  Dis Colon Rectum. 1997;  40 131-139
• 32 Kapiteijn E, Marijnen C A, Nagtegaal I D, Putter H, Steup W H, Wiggers T, Rutten H J, Pahlman L, Glimelius B, van Krieken J H, Leer J W, van de Velde C J. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer.  N Engl J Med. 2001;  345 638-646
• 33 Kockerling F, Reymond M A, Altendorf-Hofmann A, Dworak O, Hohenberger W. Influence of surgery on metachronous distant metastases and survival in rectal cancer.  J Clin Oncol. 1998;  16 324-329
• 34 Krook J E, Moertel C G, Gunderson L L, Wieand H S, Collins R T, Beart R W, Kubista T P, Poon M A, Meyers W C, Mailliard J A. Effective surgical adjuvant therapy for high-risk rectal carcinoma.  N Engl J Med. 1991;  324 709-715
• 35 Kwok H, Bissett I P, Hill G L. Preoperative staging of rectal cancer.  Int J Colorectal Dis. 2000;  15 9-20
• 36 Letschert J G, Lebesque J V, de Boer R W, Hart A A, Bartelink H. Dose-volume correlation in radiation-related late small-bowel complications: a clinical study.  Radiother Oncol. 1990;  18 307-320
• 37 Marijnen C A, Kapiteijn E, van de Velde C J, Martijn H, Steup W H, Wiggers T, Kranenbarg E K, Leer J W. Acute side effects and complications after short-term preoperative radiotherapy combined with total mesorectal excision in primary rectal cancer: report of a multicenter randomized trial.  J Clin Oncol. 2002;  20 817-825
• 38 Marsh P J, James R D, Schofield P F. Adjuvant preoperative radiotherapy for locally advanced rectal carcinoma. Results of a prospective, randomized trial.  Dis Colon Rectum. 1994;  37 1205-1214
• 39 Maurer C A, Z’graggen K, Renzulli P, Schilling M K, Netzer P, Buchler M W. Total mesorectal excision preserves male genital function compared with conventional rectal cancer surgery.  Br J Surg. 2001;  88 1501-1505
• 40 Minsky B D. Adjuvant therapy for rectal cancer ( a good first step.  N Engl J Med. 1997;  336 1016-1017
• 41 Moertel C G, Childs D S, Reitemeier R J, Colby M Y, Holbrook M A. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer.  Lancet. 1969;  2 865-867
• 42 Molls M. Pre- and postoperative radiotherapy with and without chemotherapy in rectal cancer.  Chirurg. 1994;  65 569-575
• 43 O’Connell M J, Martenson J A, Wieand H S, Krook J E, Macdonald J S, Haller D G, Mayer R J, Gunderson L L, Rich T A. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery.  N Engl J Med. 1994;  331 502-507
• 44 Overgaard M, Bertelsen K, Dalmark M, Gadeberg C C, von der Maase  H, Overgaard J, Sell A. A randomized feasibility study evaluating the effect of radiotherapy alone or combined with 5-fluorouracil in the treatment of locally recurrent or inoperable colorectal carcinoma.  Acta Oncol. 1993;  32 547-553
• 45 Pahlman L, Glimelius B. Pre- or postoperative radiotherapy in rectal and rectosigmoid carcinoma. Report from a randomized multicenter trial.  Ann Surg. 1990;  211 187-195
• 46 Pahlman L, Glimelius B, Graffman S. Pre- versus postoperative radiotherapy in rectal carcinoma: an interim report from a randomized multicentre trial.  Br J Surg. 1985;  72 961-966
• 47 Rider W D, Palmer J A, Mahoney L J, Robertson C T. Preoperative irradiation in operable cancer of the rectum: report of the Toronto trial.  Can J Surg. 1977;  20 335-338
• 48 Rodel C, Hohenberger W, Sauer R. Adjuvant and neoadjuvant therapy of rectal carcinoma. The current status.  Strahlenther Onkol. 1998;  174 497-504
• 49 Rominger C J, Gunderson L L, Gelber R D, Conner N. Radiation therapy alone or in combination with chemotherapy in the treatment of residual or inoperable carcinoma of the rectum and rectosigmoid or pelvic recurrence following colorectal surgery. Radiation Therapy Oncology Group study (76 - 16).  Am J Clin Oncol. 1985;  8 118-127
• 50 Sauer R. Adjuvant versus neoadjuvant combined modality treatment for locally advanced rectal cancer: first results of the German rectal cancer study (CAO/ARO/AIO-94).  Int J Radiat Oncol Biol Phys. 2003;  57 S124-S125
• 51 Sauer R, Fietkau R, Wittekind C, Rodel C, Martus P, Hohenberger W, Tschmelitsch J, Sabitzer H, Karstens J H, Becker H, Hess C, Raab R. Adjuvant vs. neoadjuvant radiochemotherapy for locally advanced rectal cancer: the German trial CAO/ARO/AIO-94.  Colorectal Dis. 2003;  5 406-415
• 52 Tveit K M, Guldvog I, Hagen S, Trondsen E, Harbitz T, Nygaard K, Nilsen J B, Wist E, Hannisdal E. Norwegian Adjuvant Rectal Cancer Project Group . Randomized controlled trial of postoperative radiotherapy and short-term time-scheduled 5-fluorouracil against surgery alone in the treatment of Dukes B and C rectal cancer.  Br J Surg. 1997;  84 1130-1135
• 53 Zimmermann F, Molls M. In Process Citation.  Chirurg. 2003;  74 887-896