The document discusses guidelines for screening, diagnosis, staging, adjuvant therapy, advanced disease treatment, and follow-up for colorectal cancer from both the ESMO and NCCN perspectives. It provides recommendations for screening the general and high-risk populations. It also outlines the diagnostic and staging workup, including endoscopy, biopsy, imaging, and surgical staging. Guidelines are presented for adjuvant therapy based on cancer stage. Recommendations are provided for managing both synchronous and metachronous metastatic disease, as well as rectal cancer treatment.

1. Stefano Cascinu Department of Medical Oncology Università Politecnica delle Marche Ancona, Italy Colorectal Cancer: ESMO or NCCN Guidelines?

2. Screening Diagnosis Staging Adjuvant Advanced disease Follow-up

3. Screening: general population FOBT: reduces mortality by 25% it should be offered to men and women aged 50 years until 74 years. The screening interval shoud be 1-2 years.

4. Screening: high risk population Lynch syndrome Colonoscopy starting at age 20-25 every 1-2 years. Endometrial and ovarian cancer screening may be performed yearly starting at 30-35 years. Surveillance for other Lynch-associated cancers is recommended based on the family history (upper endoscopy and abdominal US). FAP Classic FAP: Sigmoidoscopy every 2 years starting at age 12-14. Once adenomas are detected colonoscopy should be performed annually Attenuated form: Colonoscopy every two years starting at 18-20, lifelong. Once adenomas are detected it should be performed annually.

5. Diagnostic and staging workup

6. Diagnosis Endoscopy plus biopsy Virtual colonoscopy or CT colonography: not standard procedures but useful to precisely locate the tumor for the surgical approach in patients candidates for laparoscopy.

7. Physical examination Laboratory data Blood count; CEA, liver chemistry Instrumental work-up Preoperative: CT scan (chest and abdomen) Surgical staging: assessment of the liver intraoperative US, nodal spread Staging

8. A F D O J L U L V O A W N U T P and T H E R A P Y

9. Adjuvant therapy Stage III, fit patients: 6 months FOLFOX or XELOX Stage III, unfit patients 6 months Capecitabine or 5-fluorouracil Stage III elderly patients (>70Years) 6 months 5fluorouracil (?)

10. Adjuvant therapy Stage II patients low risk No adjuvant therapy Stage II patients high risk (lymph-node sampling<12; poorly differentiated tumors; vascular or lymphatic or perineural invasion; tumor presentation with obstruction or perforation; pT4) Adjuvant therapy with 5FU or FOLFOX Stage II patients MSI No adjuvant therapy or, if at high risk, FOLFOX

11. Follow-up CT scan of chest and abdomen every 6-12 months CEUS could substitute CT scan Colonoscopy performed at 1 year and then every 3-5 years PET/scan is not recommended

12. Advanced disease Aggressive therapy Symptomatic disease Borderline resectable liver metastases No aggressive therapy Indolent disease Elderly patients

13. Synchronous metastases: Resectable unresectable

14. Metachronous metastases Resectable Unresectable

15. Rectal cancer

18. Metastatic at diagnosis

20. staging Endoscopic ultrasound MRI for all rectal tumours

21. Preoperative therapy Postoperative therapy cT1-2 and some cT3 (a) above elevators, surgery alone cT3 (b); cT4, N+ preoperative chemo- radiotherapy Tis, T1 N0 local excision T2 N0 wide surgical resection T3/T4 N0 surgery and adjuvant therapy T any N1/2 surgery and adjuvant therapy