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All You Ever Wanted to Know about the Workup of Rectal Adenocarcinoma Tian Zhang, HMS IV Gillian Lieberman, MD Beth Israel Deaconess Medical Center Department of Radiology November 17, 2008 Agenda Introduce patient Discuss Rectal Adenocarcinoma, staging, and management Companion cases Stage our patient Discuss limitations of imaging Patient SK 34-year-old man, otherwise healthy, when he presents with post-prandial pain, frequent bowel movements, hematochezia, and unintentional 15-lb weight loss Urgent colonoscopy revealed large, fungating, bleeding mass; biopsied. Our Patient SK, Biopsy Invasive adenocarcinoma Desmoplasia Possible lymphatic invasion (not called small biopsies) Fibrosis BIDMC, Courtesy of A. Schell Rectal Adenocarcinoma Epidemiology – 3rd most common: ~148,000 new cases of colorectal adenoCA per yr, 40,000 cases rectal – ~50,000 deaths per year – 20% pts have distant mets at dx – Men>women, incidence rises after 40yo Risk factors: – Polyps – IBD (Ulcerative Colitis or Crohn’s) – Family history of colorectal adenocarcinoma What determines treatment and prognosis after adenocarcinoma is diagnosed? Staging of the patient’s tumor at time of diagnosis is most important! Rectal AdenoCA Staging TNM staging: T status: T0: no primary Tis: CA in situ T1: Submucosa T2: Muscularis propria T3: Perirectal fat T4: Other organs/ peritoneum Nodal status: N0: no nodes N1: <3 LNs >3mm each N2: >3 LNs >3mm each National Cancer Institute, from www.upmcancercenters.com/pdq_xml/cancer.cfm?ID=114 Met status: Mx: Not assessed M0: No mets M1: Distant mets McMahon CJ & Smith MP. Seminars in ultrasound, CT, and MRI. 2008. Stage and Prognosis 5-yr overall survival (OS) Stage 0: Tis N0 M0 Stage I: T1/T2 N0 M0 92% Stage II: T3/T4 N0 M0 73% Stage IIIA: T1-2 N1 M0 55.1% Stage IIIB: T3-4 N1 M0 35.3% Stage IIIC: anyT N2 M0 24.5% Stage IV: anyT anyN M1 8% Gloecker Ries LA, Reichman ME, Lewis DR, et al. The Oncologist. 2003; 8:541-52. What do we use to stage patients? IMAGING! Menu of Imaging Studies Endorectal Ultrasound – – Performed with endorectal balloon filled with water, with probe inside balloon Sensitive for T staging of T1/T2 tumors 94% sens and 86% spec for rectal wall invasion1 – – More experience, older technology Technically challenging, operator-dependent – – – – Performed with barium/gastromark enema, and IM glucagon to slow peristalsis Determine extent of T3 tumors, as well as invasion of pelvic organs/peritoneum: 74% sens and 96% spec1 Detects LN involvement: 66% sens and 76% spec1 Newer technology, new innovations – – For distant metastases Restaging after chemoradiation therapy – – LN involvement: 82% specific2 Technically challenging Magnetic Resonance Imaging (MRI) Computed Tomography (CT) MRI with endorectal coil 1. Bipat S, Glas AS, Slors FJ, et al. Radiology. 2004; 232(3):773-83. 2. Kwok H, Bisset IP, Hill GL. Int J Colorectal Dis. 2000; 15:9-20. Companion Patient #1: Rectal Cancer on MRI 64 yo man with BRBPR Colonoscopy: Adenoma with high-grade dysplasia Pedunculated lesion, low signal intensity on T1, some areas of high signal intensity on T2, enhances heterogeneously after gadolinium administered. Axial T1 Axial T2 Pedunculated adenocarcinoma. Sagittal T2 Post-gadolinium T1 Images from PACS, BIDMC, courtesy M. Smith Companion Patient #1: MR for T-staging Layers of rectum seen on MR with T2-weighted image: 1) Low SI: mucosa 2) High SI: submucosa 3) Low SI: muscularis propria 4) High SI: perirectal fat Mesorectal fascia Perirectal fat Muscularis propria Submucosa T2 on MR Read-out Pathology showed T1 Axial T2 Images from PACS, BIDMC, courtesy M. Smith How do we treat? Multimodality therapy – Surgical excision – Chemotherapy – Radiation therapy Let’s discuss each of these in more detail. Surgical Excision Total mesorectal excision – Transanal approach For Tis/T1 tumors – Low Anterior Resection (LAR) For T2/T3 tumors far from sphincter – Abdominoperineal Resection (APR) For T3 tumors too close to sphincter – Pelvic Exenteration For T4 tumors Chemoradiotherapy Stage I or II: Adjuvant chemotheray – FOLFOX: FOLinic acid, 5-Fluorouracil, OXaliplatin Stage III or IV: – Neoadjuvant chemotherapy: 5-fluorouracil – Neoadjuvant radiation therapy: 50.4 Gy – New chemotherapeutic tested: Cetuximab (monoclonal antibody -EGFR) German Rectal Cancer Study Group Randomized prospective trial >800 patients with T3/T4 or N+ disease randomized to neoadjuvant vs adjuvant chemoradiation – (5-FU + 50.4 Gy) Mean f/u 45.8 mos Main Results: Neoadjuvant Adjuvant p-value Local Relapse 6% 13% 0.006 APR 116 78 LAR 45/116 (39%) 15/78 (19%) 0.004 5yr OS 76% 74% 0.8 Critique: 89% pts completed neoadjuvant, 72% pts completed adjuvant Sauer R, Becker H, Hohenberger W, et al. New Engl J Med. 2004. 351(17): 1731-1740. Companion Patient #2: US Staging Anterior 51yo woman, p/w 2 months of BRBPR, assoc with diarrhea Colonoscopy: rectal mass, adenocarcinoma Interface btw balloon & mucosa (hyperechoic) Mucosa (hypoechoic) Submucosa (hyperechoic) Muscularis propria (hypoechoic) Perirectal fat (mixed echogenicity) Clinical Stage T2 Posterior Endorectal Ultrasound Tumor begins in mucosa and extends outward, without extension beyond the muscularis propria. Image from PACS, BIDMC, courtesy R. Kane & K. Krajewski Companion Patient #2: US Staging Clinical Stage T2N1 Oval lesion 5.6mm in diameter, which is hypoechoic within surrounding perirectal fat – likely lymph node. Endorectal Ultrasound Image from PACS, BIDMC, courtesy R. Kane & K. Krajewski Our Patient: SK’s US Technically challenging: Endorectal probe could not pass beyond the large mass – not fully evaluated. Visualized only the most proximal edge of tumor in anterior wall. Endorectal Ultrasound Image from PACS, BIDMC, courtesy K. Krajewski Our Patient: SK at MRI Peritoneum 7.7cm Sagittal T2 Axial T1 Tumor demonstrates low signal intensity on T1 and high signal intensity on T2. 7.7cm in superior-inferior axis. Does not invade pelvic organs; close to peritoneum. Images from PACS, BIDMC, courtesy M. Smith Our Patient: SK at MRI Axial T1 Post-gadolinium Axial T1 Post-gadolinium Infiltrated perirectal fat >3 bulky LNs, Heterogeneous enhancement, Ill-defined borders Heterogenous enhancement of mass Clinical T3N2 Images from PACS, BIDMC, courtesy M. Smith Our Patient: SK at CT I+O+ Axial CT 8mm ground glass pulmonary nodule Pulmonary nodule was not FDG-avid on PET-CT. Possible metastasis, since it may be too small to take up FDG I+O+ Axial CT Images from PACS, BIDMC, courtesy A. Sekhar Our Patient SK: Clinical Summary Tumor infiltrates perirectal fat on MRI >3 bulky lymphadenopathy, suspicious for tumor involvement Possible metastatic pulmonary nodule on CT T3N2Mx, Stage IIIC Treatment: – Neoadjuvant chemoradiotherapy – Surgical excision – Close follow-up for pulmonary nodules Let’s take a look at how CT definitively evaluates for distant metastatic lesions. Companion patient #3: Distant Metastasis on CT 37yo man p/w rectal bleeding and 7-lb weight loss Colonoscopy: Large mass, biopsied, pathology: adenocarcinoma T3N2M1 Stage 4 2.8cm x 2.4cm lesion in posterior rectal wall I+O+ axial CT >3 bulky perirectal lymph nodes, all >3mm Multiple round, hypoattenuated lesions, hypovascular compared to surrounding hepatic tissue with dual vascular supply. Largest lesion 3.1cm x 3.3cm Image from PACS, BIDMC, courtesy M. Smith Finally, let’s discuss some limitations of imaging. Room for improvement Overestimation of clinical stage: – German Rectal Study: 18% of cT3/T4 or N1 disease had T1N0 or T2N0 on pathology – Possible over-treatment with chemorads Recent study1 shows underestimated clinical stage: – 188 pts with cT3N0 (Stage II), 22% had undetected perirectal LN involvement on pathology (Stage III) – These patients may have benefited from chemoradiation treatment Reliance on imaging for staging only as good as imaging itself – there is room for improvement. New innovations in MRI technology in the pipeline (like iron oxide nanoparticles) to image lymph nodes and tumor extension with greater sensitivity and specificity. 1. Guillem JG, Diaz-Gonzalez JA, Minsky BD, et al. J Clin Oncol. 2008. 26:368-373. Summary Imaging of rectal adenocarcinoma determines staging, which is important for treatment and prognosis of these patients. Complementary information can be obtained from endorectal ultrasound, MRI, and CT to stage the patient completely. Up to 40% of patients are clinically staged with earlier or more advanced stage than stage shown on pathology after excision – imaging may be able to perform better in the future. References Ahnen DJ & Macrae FA. Clinical manifestations, diagnosis, and staging of colorectal cancer. UpToDate. 2008. www.utdonline.com. Accessed 11/15/08. Bipat S, Glas AS, Slors FJ, et al. Rectal cancer: local staging and assessment of lymph node involvement with endoluminal US, CT, and MR imaging – a meta-analysis. 2004; 232(2): 773-83. Gloeckler Reis LA, Reichman ME, Lewis DR, et al. Cancer survival and incidence from the surveillance, epidemiology, and end results program. Oncologist. 2003; 8(6): 541-52. Guillem JG, Diaz-Gonzalez JA, Minsky BD, et al. cT3N0 rectal cancer: potential overtreatment with preoperative chemoradiotherapy is warranted. J Clin Oncol. 2008; 26(3): 368-73. Krajewski KM & Kane RA. Ultrasound staging of rectal cancer. Approv for pub, Seminars in Ultrasound, CT, & MRI. 2008. Kwok H, Bissett IP, Hill GL. Preoperative staging of rectal cancer. Int J Colorectal Dis. 2000. 15:9-20. McMahon CJ & Smith MP. Magnetic resonance imaging in locoregional staging of rectal adenocarcinoma. Approv for pub, Seminars in Ultrasound, CT, & MRI. 2008. Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative chemoradiotherapy for rectal cancer. New Engl J Med. 2004; 351: 1731-40. Acknowledgments Dr. Katie Krajewski Dr. Robert Kale Dr. Andrew Schell Dr. Aarti Sekhar Dr. Marty Smith Dr. Gillian Lieberman Maria Levantakis