Moderately Advanced Rectal Cancer

1. Moderately Advanced Rectal Cancer Amr Aref, MD Chief, Radiation Oncology Van Elslander Cancer Center Ascension St. John Hospital

2. Moderately Advanced Rectal Cancer T3 N0 – N1 T2 N1 Very Distal T2N0 N < 1 cm

3. Locally Advanced Rectal Cancer CONVENTIONAL TREATMENT Concurrent Chemo-radiotherapy (No Restaging) SURGICAL RESECTION (TME) Adjuvant Chemotherapy

4. Locally Advanced Rectal Cancer RESULT OF CONVENTIONAL TREATMENT LOCAL RECURRENCE < 5% Distant failure 20-25 % Sphincter saving surgery > 75 %

5. Locally Advanced Rectal Cancer GOOD TUMOR CONTROL BUT: Still, 15-25% will have permanent colostomy Most patients will have temporary colostomy Only 50 % of patients will have full dose of adjuvant chemotherapy Long term Quality of Life issues

6. Moderately Advanced Rectal Cancer Long Term Toxicity • Urinary Symptoms • Sexual Dysfunction (for both men and women) • Bowel Symptoms (LARS)

7. Moderately Advanced Rectal Cancer Low Anterior Resection Syndrome • Bouts of urgent and increased bowel movements • Uncontrolled passage of gas • Unable to distinguish between passing gas or stool • Urgency • Incontinence

8. Moderately Advanced Rectal Cancer • Affects about 50% of patients • Particularly frequent and severe for low anastomosis • LARS symptoms do not improve with time Low Anterior Resection Syndrome

9. Locally Advanced Rectal Cancer Rationale for Organ Preservation & avoidance of TME Avoidance of long term toxicity. The observation that 15-30 % of resected lesions after TME have no microscopic disease.

10. Locally Advanced Rectal CancerOrgan Preservation Prerequisites for success: • Increase the number of patients with no residual tumor after neoadjuvant therapy from 15-20% to > 40-50 % • Neoadjuvant Chemotherapy, ie Total Neoadjuvant Approach • Increase waiting time between completion of radiation and surgery • Increase radiation dose

11. Locally Advanced Rectal CancerOrgan Preservation Prerequisites for success: • Identify clinically those patients • Improve QUALITY OF LIFE • MAINTAIN EXCELLENT LOCAL CONTROL

12. Moderately Advanced Rectal Cancer Organ Preservation at St. John FOLFOX x 6 Restage Chemo-RT Restage CR <CR TME Organ preservation

13. Locally Advanced Rectal Cancer NEOADJUVANT CHEMOTHERAPY • HOW LONG ?

14. Locally Advanced Rectal Cancer NEOADJUVANT CHEMOTHERAPY • RISK OF TUMOR PROGRESSION? Progression not observed

15. Locally Advanced Rectal Cancer NEOADJUVANT CHEMOTHERAPY • PATIENT IS TOO SYMPTOMATIC TO DELAY RT Excellent palliation of symptoms

16. Locally Advanced Rectal Cancer NEOADJUVANT CHEMOTHERAPY • WILL FOLFOX ACTUALLY INCREASE No. Of PATIENTS WITH pCR? pCR 5/10 = 50 %

17. Moderately Advanced Rectal Cancer Organ Preservation FOLFOX x 6 Restage Chemo-RT Restage CR >CR TME Organ preservation

18. Moderately Advanced Rectal Cancer Restaging after completion of neoadjuvant therapy is important because organ preservation is offered only to patients with CR. Determination of CR is easier said than done

19. Moderately Advanced Rectal Cancer RESTAGING • How long should you wait after Chemo-RT? LE Protocol : 12 Weeks WW Protocol : up to 20 weeks • About 75% of pCR cases will have mucosal abnormalities. • Negative Mucosal biopsy is meaningless.

20. Moderately Advanced Rectal Cancer RESTAGING Digital Exam Proctoscopy MRI : Experienced & Intersted Radiologist Special Rectal protocol ( Not MRI of Pelvis ) T2 & DWI No need for IV contrast EUS ?

21. Memorial Sloan Kettering Regression Schema

22. Moderately Advanced Rectal Cancer Organ Preservation • TRANSANAL FULL THICKNESS LOCAL EXCISION • WATCHFUL WAITING

23. Locally Advanced Rectal Cancer FULL THICKNESS LOCAL EXCISION • pCR at the primary site infers pCR at the mesorectum in this patients group • If pCR is confirmed at the primary site, local and mesorectal control is between 100%-95%

24. Organ preservation FULL THICKNESS LOCAL EXCISION • Certainty of response • Several retrospective and prospective series from several institutions • Safety proven by a randomized trial

25. Moderately Advanced Rectal Cancer Organ Preservation • TRANSANAL FULL THICKNESS LOCAL EXCISION Should we abandon this procedure ( in favor of WW ) because it is too morbid ?

27. Moderately Advanced Rectal Cancer Organ Preservation • TRANSANAL FULL THICKNESS LOCAL EXCISION. Is it too morbid ? Some less known studies report acceptable Complications.

28. Local Excision St. John Experience Tumor not extending to dentate line Tumor extending to dentate line 2/8 patients with minor complications 2/2 patients with severe complications

29. FULL THICKNESS LOCAL EXCISION St. John Approach: • Limited Radiation field • Radiation dose not above 50.4 Gy • No Surgical mucosal margin around the residual abnormality • No Deep dissection into mesorectal fat • No dissection through the dentate line

30. FULL THICKNESS LOCAL EXCISION St. John Approach: • Robotic assisted Surgery • Operative time about 60 minutes, minimal blood loss • 24 hours hospital stay • NO TEMPORARY COLOSTOMY !! • Normal diet on the 1st postoperative day

31. FULL THICKNESS LOCAL EXCISION St. John Approach: • Local Excision in this setting, is a biopsytoconfirm pCR. • Local Excision has NO therapeutic role • TME is recommended to patients with >ypT1-R0 after local excision

32. Locally Advanced Rectal Cancer FULL THICKNESS LOCAL EXCISION Since determination of CCR is difficult, why not perform LE on every patient and offer TME to patients with residual microscopic disease ?

33. Management of Moderately Advanced Rectal Cancer Organ preservation • Watchful Waiting • Habr Gama Approach • Brazilian approach

34. Organ Preservation WATCHFUL WAITING • Avoids local excision complications • Better Quality of Life? • 20% of patients will demonstrate tumor regrowth Usually Endoluminal Excellent eventual local control Excellent Disease free survival

35. Organ Preservation WATCHFUL WAITING • Very close and well coordinated follow up Patients compliance issues ? • Limited experience in few centers • No randomized trial • Increased risk of distant metastases in patients who develop future regrowth?

36. Organ Preservation WATCHFUL WAITING Recognized by NCCN Should NCCN also recognize Local Excision ?

37. Organ Preservation WATCHFUL WAITING Radiation dose escalation is used often ,in addition to neoadjuvant Chemotherapy to increase CR (No dose escalation if Local Excision is planned)

38. Transanal Endoscopic Brachytherapy Dose Rate CXB unique RT = high precision – eye guided small volume (5cm3): High Dose/Fraction

39. CONTACT THERAPY

40. ST. JOHN APPROACH • All patients with moderately advanced cancer are offered an opportunity for organ preservation. TME is no longer routine. • Very distal tumors are approached by watchful waiting. • Other tumors are approached by LE.

41. ST. JOHN EXPERIENCE • TRANSANAL FULL THICKNESS LOCAL Excision 10 patients (some off protocol patients) • WATCHFUL WAITING 1 patient • Accrued but not completed entire treatment course 3 patients So far no local or distant recurrence but follow up is very short

42. CONCLUSION • TME Remains The Standard of Care. It is reasonable to offer patients with cCR an opportunity for organ preservation • Neoadjuvant Chemotherapy (3-4 months) is preferred over adjuvant chemotherapy • LE after neoadjuvant chemo-RT can be safe if performed with careful radiation and surgical technique

43. THANK YOU

44. Patients Developing Complications

45. Moderately Advanced Rectal Cancer Organ Preservation at St. John FOLFOX x 6 Restage Chemo-RT Restage CR >CR TME Organ preservation

46. Locally Advanced Rectal Cancer NEOADJUVANT CHEMOTHERAPY • How Long? • Risk of tumor progression while on chemo • Patient is too symptomatic to start with chemo and delay radiation. • Will chemo actually increase patients with pCR?