Zusammenfassung
Hintergrund
Für Patienten mit Rektumkarzinom und kompletter Remission (ypT0) oder guter Response mit intramuralem Residualtumor (ypT1–2) nach neoadjuvanter Radiochemotherapie (RCT) wurden – zur Reduktion postoperativer Funktionseinschränkungen – wiederholt lokale Operationsverfahren als Alternative zur totalen mesorektalen Exzision (TME) vorgeschlagen. Ziel dieser Untersuchung war eine vergleichende Analyse von Frequenz und tumorabhängiger Lokalisation mesorektaler Lymphknotenmetastasen bei Patienten mit kompletter Remission (ypT0), intramuralem (ypT1–2) und wandüberschreitendem Residualtumor (ypT3–4).
Patienten und Methoden
Patienten mit cUICC-II/III-Rektumkarzinom (n = 81), die innerhalb der CAO/ARO/AIO-04-Studie behandelt wurden, wurden prospektiv evaluiert. Es erfolgte eine intensivierte histopathologische Aufarbeitung mit vollständiger mikroskopischer Untersuchung des mesorektalen Fettgewebskompartimentes. Die stadienabhängige Inzidenz und die intramesorektale Verteilung lymphogener Metastasen in Abhängigkeit vom Primärtumor wurden erhoben.
Ergebnisse
Ein wandüberschreitendes Tumorwachstum (ypT3–4) zeigten 62 % der Patienten, 25 % hatten eine deutliche partielle Remission des Primarius mit intramuralen Residuen (ypT1–2) und 14 % wiesen eine komplette Remission (ypT0) auf. Insgesamt wurden 28 ± 13,7 Lymphknoten (LK) pro TME-Präparat detektiert. Zwar war die Inzidenz von LK-Metastasen in der ypT3–4-Gruppe mit 40 % höher, jedoch wiesen immerhin 25 % der Patienten mit intramuralem Residualtumor (ypT1–2) im Mittel 2,2 LK-Metastasen auf, von denen 55 % distanziert zum Primarius im proximalen Mesorektum lokalisiert waren. Patienten mit Komplettresponse (ypT0) wiesen keine residuellen LK-Metastasen auf.
Diskussion
Patienten mit guter Response (ypT1–2) nach neoadjuvanter RCT haben in bis zu 25 % der Fälle residuelle mesorektale LK-Metastasen. Lokale Operationsverfahren wären im Vergleich zur TME mit einem erhöhten Risiko für ein lokales Tumorrezidiv vergesellschaftet. Bisher fehlen valide Selektionskriterien dafür, welche Patienten onkologisch sicher mit organerhaltenden Verfahren operiert werden könnten.
Abstract
Background
For patients with rectal cancer and complete remission (ypT0) or with good response and residual tumor restricted only to the bowel wall (ypT1–2) after neoadjuvant chemoradiotherapy (CRT), local excision has been suggested as an alternative to avoid the significant morbidity and functional deficits associated with total mesorectal excision (TME). The aim of this investigation was to investigate the incidence, distribution and tumor-related localization of mesorectal lymph node (LN) metastases in TME specimens with complete remission (ypT0), intramural (ypT1–2) and extramural (ypT3–4) residual tumor tissue.
Patients and methods
Specimens of TME from 81 patients with locally advanced rectal cancer (UICC II-III) undergoing neoadjuvant CRT within the phase III German rectal cancer trial CAO/ARO/AIO-04 were prospectively evaluated. The entire mesorectal compartment was microscopically screened after complete paraffin embedding. The number and localization of all detectable LN metastases were documented in relation to the primary tumor.
Results
Whereas 50 patients (62 %) had ypT3–4 rectal cancer after neoadjuvant CRT, 20 patients (25 %) presented with residual tumor within the bowel wall (ypT1–2), 11 patients (14 %) had pathological complete remission (ypT0), an average of 28 ± 13.7 LN were detected per specimen and 25 patients (31 %) had residual LN metastases after CRT. Although the incidence of LN metastases was higher in the ypT3–4 group (40 %), 25 % of patients in the ypT1–2 group with intramural residual tumor had a mean number of 2.2 residual LN metastases of which 55 % were located far from the primary lesion in the proximal mesorectum. None of the patients with ypT0 status (complete response) had residual LN metastases.
Conclusion
Even in patients with good response and post-CRT tumor tissue restricted only to the bowel wall (ypT1–2), there is still a considerable risk for residual LN metastases. Local excision of residual rectal cancer was accompanied by a higher rate of local failure and radical surgery with TME should remain the standard treatment in these patients. To date, valid selection criteria for patients eligible for organ-sparing surgery are still lacking.
Literatur
Arbman G, Nilsson E, Hallbook O et al (1996) Local recurrence following total mesorectal excision for rectal cancer. Br J Surg 83:375–379
Chen Z, Liu Z, Deng X et al (2012) Chromosomal copy number alterations are associated with persistent lymph node metastasis after chemoradiation in locally advanced rectal cancer. Dis Colon Rectum 55:677–685
Dahlberg M, Glimelius B, Pahlman L (1999) Changing strategy for rectal cancer is associated with improved outcome. Br J Surg 86:379–384
Fokas E, Liersch T, Fietkau R et al (2014) Tumor regression grading after preoperative chemoradiotherapy for locally advanced rectal carcinoma revisited: updated results of the CAO/ARO/AIO-94 trial. J Clin Oncol 32:1554–1562
Friel CM, Cromwell JW, Marra C et al (2002) Salvage radical surgery after failed local excision for early rectal cancer. Dis Colon Rectum 45:875–879
Garcia-Aguilar J, Chen Z, Smith DD et al (2011) Identification of a biomarker profile associated with resistance to neoadjuvant chemoradiation therapy in rectal cancer. Ann Surg 254:486–492 (discussion 492–483)
Habr-Gama A, Gama-Rodrigues J, Sao Juliao GP et al (2014) Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy on local disease control. Int J Radiat Oncol Biol Phys 88:822–828
Habr-Gama A, Perez RO, Nadalin W et al (2004) Operative versus nonoperative treatment for stage 0 distal rectal cancer following chemoradiation therapy: long-term results. Ann Surg 240:711–717 (discussion 717–718)
Heald RJ, Husband EM, Ryall RD (1982) The mesorectum in rectal cancer surgery–the clue to pelvic recurrence? Br J Surg 69:613–616
Hoerske C, Weber K, Goehl J et al (2010) Long-term outcomes and quality of life after rectal carcinoma surgery. Br J Surg 97:1295–1303
Jayne DG, Brown JM, Thorpe H et al (2005) Bladder and sexual function following resection for rectal cancer in a randomized clinical trial of laparoscopic versus open technique. Br J Surg 92:1124–1132
Koh DM, Chau I, Tait D et al (2008) Evaluating mesorectal lymph nodes in rectal cancer before and after neoadjuvant chemoradiation using thin-section T2-weighted magnetic resonance imaging. Int J Radiat Oncol Biol Phys 71:456–461
Lange MM, Maas CP, Marijnen CA et al (2008) Urinary dysfunction after rectal cancer treatment is mainly caused by surgery. Br J Surg 95:1020–1028
Lange MM, van de Velde CJ (2008) Faecal and urinary incontinence after multimodality treatment of rectal cancer. PLoS Med 5:e202
Maas M, Beets-Tan RG, Lambregts DM et al (2011) Wait-and-see policy for clinical complete responders after chemoradiation for rectal cancer. J Clin Oncol 29:4633–4640
Maas M, Nelemans PJ, Valentini V et al (2010) Long-term outcome in patients with a pathological complete response after chemoradiation for rectal cancer: a pooled analysis of individual patient data. Lancet Oncol 11:835–844
Noh JM, Park W, Kim JS et al (2014) Outcome of local excision following preoperative Chemoradiotherapy for clinically T2 distal rectal cancer: A Multicenter retrospective study (KROG 12-06). Cancer Res Treat 46:243–249
Park IJ, You YN, Skibber JM et al (2013) Comparative analysis of lymph node metastases in patients with ypT0-2 rectal cancers after neoadjuvant chemoradiotherapy. Dis Colon Rectum 56:135–141
Perez RO, Habr-Gama A, Lynn PB et al (2013) Transanal endoscopic microsurgery for residual rectal cancer (ypT0–2) following neoadjuvant chemoradiation therapy: another word of caution. Dis Colon Rectum 56:6–13
Perez RO, Habr-Gama A, Proscurshim I et al (2007) Local excision for ypT2 rectal cancer–much ado about something. J Gastrointest Surg 11:1431–1438; discussion 1438–1440
Perez RO, Pereira DD, Proscurshim I et al (2009) Lymph node size in rectal cancer following neoadjuvant chemoradiation–can we rely on radiologic nodal staging after chemoradiation? Dis Colon Rectum 52:1278–1284
Rodel C, Liersch T, Becker H et al (2012) Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol 13:679–687
Rodel C, Martus P, Papadoupolos T et al (2005) Prognostic significance of tumor regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol 23:8688–8696
Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740
Sauer R, Liersch T, Merkel S et al (2012) Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol 30:1926–1933
Sobin LH (2003) TNM, sixth edition: new developments in general concepts and rules. Semin Surg Oncol 21:19–22
Sprenger T, Rothe H, Becker H et al (2013) Lymph node metastases in rectal cancer after preoperative radiochemotherapy: impact of intramesorectal distribution and residual micrometastatic involvement. Am J Surg Pathol 37:1283–1289
Verseveld M, de Graaf EJ, Verhoef C et al (2015) Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery (CARTS study). Br J Surg 102:853–860
Wallner C, Lange MM, Bonsing BA et al (2008) Causes of fecal and urinary incontinence after total mesorectal excision for rectal cancer based on cadaveric surgery: a study from the Cooperative Clinical Investigators of the Dutch total mesorectal excision trial. J Clin Oncol 26:4466–4472
Weiser MR, Landmann RG, Wong WD et al (2005) Surgical salvage of recurrent rectal cancer after transanal excision. Dis Colon Rectum 48:1169–1175
Zhao RS, Wang H, Zhou ZY et al (2014) Restaging of locally advanced rectal cancer with magnetic resonance imaging and endoluminal ultrasound after preoperative chemoradiotherapy: a systemic review and meta-analysis. Dis Colon Rectum 57:388–395
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
T. Sprenger, H. Rothe, T. Beissbarth, L.-C. Conradi, A. Kauffels, K. Homayounfar, C. L. Behnes, C. Rödel, T. Liersch und M. Ghadimi geben an, dass kein Interessenkonflikt besteht.
Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.
Additional information
Diese Studie wurde von der Deutschen Forschungsgemeinschaft (KFO 179) unterstützt.
Rights and permissions
About this article
Cite this article
Sprenger, T., Rothe, H., Beissbarth, T. et al. Lymphknotenmetastasen beim ypT1/2-Rektumkarzinom nach neoadjuvanter Radiochemotherapie. Chirurg 87, 593–601 (2016). https://doi.org/10.1007/s00104-016-0170-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00104-016-0170-9