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Controversies in the management of rectal cancers

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Controversies in the management of rectal cancers

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Management of rectal cancers have undergone a huge paradigm shift over the last decade. One the one hand, it has opened up new avenues; it also has thrown up new challenges and controversies

Management of rectal cancers have undergone a huge paradigm shift over the last decade. One the one hand, it has opened up new avenues; it also has thrown up new challenges and controversies

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Controversies in the management of rectal cancers

  1. 1. CONTROVERSIES IN THE MANAGEMENT OF RECTAL CANCER Dr Ajeet Kumar Gandhi MD (AIIMS), DNB (Gold Medalist), ECMO UICCF (MSKCC,USA) Assistant professor, Radiation oncology Dr RMLIMS, Lucknow
  2. 2.  MRI as a staging tool in rectal cancers  MERCURY Trial (JCO 2014)  Identify patients with potentially involved CRM ( ≲ 1 mm)  Prognostic (5-year OS 62.2% vs. 42.2%)
  3. 3.  Neo-adjuvant/adjuvant therapies have become engraved in the management of rectal cancers  T1-2N0M0: Local Failure rates <10%  T3N0M0, T1N1M0: LFR 15-35%  T3-4N1-2M0: LFR 45-65%  1990 NCI Consensus statement  “Combined postoperative chemotherapy and radiation therapy improves local control and survival in stage II/III rectal cancer patients and is recommended”  Advances over last two decades  TME and improvement in surgical techniques  Adaptation of neo-adjuvant therapies versus post-operative therapy  Advances in radiation planning and delivery  Long term morbidities of intensified treatment approaches
  4. 4. PARADOX DE- ESCALATION/INTENSIFICATION/INDIVIDUALIZATIO
  5. 5.  Patients with T1-2N0M0 spared of neo-adjuvant therapies  Neoadjuvant CT, RT or a combination of this is usually used for locally advanced rectal cancers (T3-4N0-2M0)  Can we avoid neo-adjuvant therapy in select patient subsets of LARC?  Can radiotherapy (pre-op) be avoided in subset of patients after a good clinical response to neo-adjuvant chemotherapy?
  6. 6. Lancet 2009; 373: 811–20
  7. 7.  Can we avoid neo-adjuvant therapy in select patient subsets of LARC  Intermediate risk rectal cancers  MRI must for staging and risk stratification  T3N0 patients with no CRM threatening, high lying tumors (5-12 cm from anal verge)  Insufficient data upfront
  8. 8. Schrag D, Weiser M, Goodman KA, et al. J Clin Oncol, 2014
  9. 9.  Can radiotherapy (pre-op) be avoided in subset of patients after a good clinical response to neo-adjuvant chemotherapy in LARC?  Promising data from MSKCC series  Ongoing PROSPECT trial would yield answers  Remains investigational outside a clinical trial
  10. 10.  Can we further improve outcomes by addressing micro metastatic systemic disease as well as the primary tumor with upfront chemotherapy rather than adjuvant chemotherapy?  Concerns: Pros and cons  Do you practice this in your setting: planned/owing to RT waiting time?
  11. 11. Chua, Lancet Oncol;2010 Fernandez-Martos, J ClinOncol;2010
  12. 12. Chua, Lancet Oncol;2010
  13. 13. Fernandez-Martos, J ClinOncol;2010
  14. 14. Fernandez-Martos, J ClinOncol;2010
  15. 15. JAMA Oncol, 2018
  16. 16. • pCR rates were 18% versus 10% in NACT arm vs NACTRT • LCR rates were 100% vs. 88.9% at median follow up of 28 months IJROBP, Volume 105, Number 1S, Supplement 2019
  17. 17. Shweta Srivastava, Madhup Rastogi, Rohini Khurana, Ajeet Gandhi, Rahat Hadi, Shantanu Sapru, et al
  18. 18. NCCN Guideline 2018
  19. 19. Ongoing TNT NRG-GI002 Schema
  20. 20.  Can we further improve outcomes by addressing micro metastatic systemic disease as well as the primary tumor with upfront chemotherapy rather than adjuvant chemotherapy?  Promising results from phase II RCT and single institutional series  TNT may increase the rates of pCR and chances of receipt of adjuvant chemotherapy  NCCN recommendation (Category 2A) in selected patients  Evolving role on patient selection and results of ongoing NRG trial
  21. 21.  How often do you encounter requests of non-operative management from your patients?  Can surgery be avoided in the settings of complete clinical response to pre-operative treatment in LARC?  Have you treated/Do you offer this to your patients outside a clinical trial?
  22. 22. J Gastrointestinal Surgery; 2006 Patients with distal rectal adenocarcinoma, located 0-7 cm from the anal verge Patients with complete tumour regression sustained for at least 12 months were considered stage c0 and were included in the study
  23. 23. • All patients underwent neoadjuvant chemoradiation consisting of 54 Gy of radiation and 6 cycles of chemotherapy as described previously. • In brief, 45 Gy of radiation was delivered by a 3-field approach with daily doses of 1.8 Gy on weekdays to the pelvis, followed by a 9-Gy boost to the primary tumor and perirectal tissue (54 Gy total). • Concomitantly, patients received 3 cycles of bolus 5-FU (450 mg/m2) and a fixed dose of 50 mg of leucovorin for 3 consecutive days every 3 weeks. After completion of radiation, patients received 3 additional identical cycles of chemotherapy every 3 weeks
  24. 24. Smith JJ et al, ASCO GI, 2015 Non-operative Management: MSKCC experience
  25. 25. Non-operative Management: MSKCC experience Smith JJ et al, ASCO GI, 2015
  26. 26. Lancet 2018; 391: 2537–45 o 1009 patients (2015-2017) o 880 patients (87%) with complete clinical response included o Median follow up: 3.3 years o 2 years local regrowth rate: 25.2% (95% CI 22.2-28.5%) o 88% local regrowth diagnosed in first 2 years o 97% of local regrowth were in bowel wall o 5 Year OS 85% and DFS 94%
  27. 27. Challenges in predicting a pCR • Surgery: Still the only means to reliably detect it • Clinical response: discordance with path response • Post-RT versus residual disease • DRE, Endoscopy, EUS, CT, MRI, PET • Only 25% of clinical CR were Pathological CR: MSKCC series • Biopsy after CRT difficult to interpret • Positive: Unknown clinical significance of few viable cells • Negative: Sampling error
  28. 28. Limitations and more challenges: NOM • Limited duration of follow up • Patient selection criteria not well established • Algorithm of surveillance • Timing for residual disease detection (4-6 wks. vs. 24 wks.) • Interval and duration of surveillance • MRI and sigmoidoscopy every three months first year and every 6 months for 5 years • Heterogeneity of studies in terms of defining and identifying CR • Definition of CR: Endoscopy, Biopsy, Endorectal USG, DRE
  29. 29.  Evidence not robust enough to suggest outside a clinical trial  Growing demand of patients and promising outcome from single institutional series and international database  NOM has to be done in centers with clinical expertise and experience for treating rectal cancers  Ongoing Canadian and MSKCC prospective trials would help further understand its future role
  30. 30. • How often do you use SCRT in your clinical practice and which patients? • How do you choose between long course CTRT versus CTRT? • Do you practice SCRT followed by delayed surgery in your practice?
  31. 31. SCRT Trials: Existing evidence
  32. 32. Polish II Multicentric Phase III study
  33. 33. Polish II Multicentric Phase III study
  34. 34. Stockholm III Trial
  35. 35. Stockholm III Trial
  36. 36. Long term effects of SCRT
  37. 37. 2018 NCCN Guidelines: LARC Controversies 02: tOTAL NEOADJUVANT THERAPY IN LARC
  38. 38. RAPIDO Trial: Ongoing
  39. 39. • SCRT remains one of the treatment options for LARC • Resource constrained setting may rely more on this (IAEA Trial) • SCRT followed by delayed surgery is associated with less complications and higher pCR rates as compared to immediate surgery • Long term toxicities remain a concern!! • Exciting option for patients with synchronous oligo metastatic disease • Future studies testing the incorporation of SCRT in total neoadjuvant approach (SCRT->CT->Surgery)
  40. 40. More controversies and challenges • Adjuvant chemotherapy in LARC treated with long course CTRT • Do all patients benefit? • Issues of tolerance and dose intensity? • Can subset of patients be avoided of adjuvant CT • Lateral pelvic lymph node disease in LARC • Identify patients at high risk • Lateral pelvic wall dissection • Radiotherapy intensification with SIB-IMRT • Chemotherapy intensification with or without targeted therapy • Intraoperative radiotherapy • LARC with synchronous metastasis/oligometastatic • Sequencing of Surgery/CT/RT • Evolving role of SCRT • Sequencing of surgery for primary and metastatic disease
  41. 41. Thank you !! Time to look beyond the horizon

Editor's Notes

  • Post-operative RT is not usually part of the planned management and usually reflects poor preoperative decisions, unexpected surgical or histopathologic findings, or both.
  • In adition, for patients with a high risk of metastatic disease, the integration of more active chemotherapy into the preoperative setting has become more attractive either in addition to or as an alternative for chemoradiotherapy

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