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
Basic structure of hair and hair growth cycle.pptx
Controversies in the management of rectal cancers
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. 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. 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
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?
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
10. 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
12. 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?
18. • 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
22. 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
23. 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?
26. 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
27. • 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
29. Smith JJ et al, ASCO GI, 2015
Non-operative Management: MSKCC experience
32. 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%
33. 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
34. 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
35. 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
36. • 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?
45. • 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)
46. 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
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