Journal Club

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Journal Club

• 17th March, 2003
• Dr Ramon Varcoe

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Which rectal cancers should
be treated with
PREOPERATIVE RADIATION ?
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BackgroundThere is evidence to support the
rationale of giving radiotherapy before surgery
while the SI is mobile and not fixed in the
pelvis with adhesions..

• Swedish Rectal Cancer Trial. NEJM. 1997
• 1168 patients with rectal cancer stages I-III
• Preop short course RT improved LR (11 vs 27) and
  survival (58 vs 48)
• Camma etal. (meta-analysis) JAMA. 2000
• 14 studies/6426 patients
• Improved LR (OR 0.49/Plt0.001) and overall
  mortality (OR 0.84/P0.03) with PRT

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Background

• Camma etal. (meta-analysis) JAMA 2000
• 14 studies, 6426 patients
• Early rectal cancers (T1/T2) show no benefit from
  preop radiation therapy
• Lopez-Kostner etal. (Cleveland) Surgery 1998
• Upper third rectal cancer behave like colon
  cancer in terms of LR and disease profile
• Marsh etal. (Manchester) DCR 1994
• 284 patients. Prospective, randomized controlled
  trial
• Locally advanced (T4) low rectal cancers show
  reduced LR with preop RT but overall survival is
  similar

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PROBLEMS

• Inaccurate PREOPERATIVE STAGING
• (ERUS is most sensitive for bowel wall invasion,
  86 by Napoleon etal BJS 1991)
• At the time of publication all trials that
  demonstrate benefits of PreopRT do not describe
  formal TME.
• Most Trials therefore have LR 25-50 instead of
  the expected 4-9 with TME
• Nb.The Dutch Colorectal Cancer Group Trial has
  since been published using TME and confirming the
  survival benefits seen in the Swedish trial

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Preoperative Radiotherapy Improves Survival for
Patients Undergoing Total Mesorectal Excision for
Stage T3 Low Rectal Cancers

• by C.Delaney, I.Lavery, A.Brenner, J.Hammel,
  A.Senagore, R.Noone and V.Fazio
• Cleveland Clinic, Ohio, USA
• Annals of Surgery
• 236(2), 2002, 203-7

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OBJECTIVE

• Examine effects of Preoperative Radiotherapy
  (PRT)
• ON
• T3 low rectal cancers
• Undergoing TME rectal excision

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STUDY DESIGN

• Retrospective
• 1980-2001
• Adenocarcinoma of rectum lt8cm from AV
• Undergoing Anterior Resection or APR
• T3 tumours on histology
• T3 on ERUS (cohort group)
• Excluded if
• Proven metastatic disease
• Had Post-op radiotherapy or chemotherapy

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STUDY DESIGN

• Long course radiotherapy
• 40-50 Gy over 4-6 weeks then surgery 4-6 weeks
  later
• Total mesorectal excision (TME) surgery
• Excision of the mesorectum with its investing
  fascial layer preserving the pre-sacral autonomic
  nerves and Denonvilliers fascia

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RESULTS

• 259 patients
• 92 had PRT, 167 did not
• Matched with similar but not identical
  demographic data (see table 1), similar tumour
  details and surgical procedures
• An ultrasound control group was incorporated to
  attempt to nullify the potential for histological
  down staging with PRT

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The treatment group is significantly younger
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Overall survival benefit after treatment with PRT
Cancer specific survival benefit also dominated
by node negative tumours
Local recurrence rates were also marginally
reduced with PRT
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Overall survival is significantly improved by
giving radiation in this 2-5 cm group
Show me the money
In the same group cancer specific survival is
also significantly improved
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Again overall survival is improved with PRT,
driven by the node negative group
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CONCLUSIONS

• T3 tumours less than 8 cm from AV should be
  treated with PRT
• Especially node negative tumours
• Especially tumours 2-5 cm
• Insufficient evidence to exclude subgroups of T3
  tumours from treatment at this stage

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Trial strengths

• Two established surgeons
• Standardised technique of TME
• Large numbers

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Problems with this trial

• Retrospective
• 38 of the 92 that had PRT also had simultaneous
  chemotherapy (interestingly they had a worse OS
  53.2 vs 71.0)
• Downstaging effect of PRT may affect histology
• This potential histology inaccuracy creates a
  crucial flaw in the study design

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The next question is "Do we use long course or
short course radiation ?"
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The Trans-Tasman Radiation Oncology Group (TROG)
TrialA Randomised Trial of Preoperative
Radiotherapy for Stage T3 Adenocarcinoma of
Rectum
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TROG trial

• Commenced July 2001
• Multicentre (17 so far)
• More than 100 patients recruited

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The End