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Journal Club. 17 th March, 2003 Dr Ramon Varcoe. Which rectal cancers should. be treated with . PREOPERATIVE RADIATION ?. Background… “ There is evidence to support the rationale of giving radiotherapy before surgery while the SI is mobile and not fixed in the pelvis with adhesions..”.

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journal club

Journal Club

17th March, 2003

Dr Ramon Varcoe

slide2
Which rectal cancers should

be treated with

PREOPERATIVE RADIATION ?

slide3
Background…“There 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/P<0.001) and overall mortality (OR 0.84/P0.03) with PRT
background
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
problems
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

slide6
“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

objective
OBJECTIVE
  • Examine effects of Preoperative Radiotherapy (PRT)

ON

  • T3 low rectal cancers
  • Undergoing TME rectal excision
study design
STUDY DESIGN
  • Retrospective
  • 1980-2001
  • Adenocarcinoma of rectum <8cm 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
study design9
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 Denonvillier’s fascia

results
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
slide11
The treatment group is

significantly younger

slide12
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

slide13
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

conclusions
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
trial strengths
Trial strengths…
  • Two established surgeons
  • Standardised technique of TME
  • Large numbers
problems with this trial
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

slide18
The next question is

"Do we use long course

or short course radiation ?"

slide19
The Trans-Tasman Radiation Oncology Group (TROG) Trial“A Randomised Trial of Preoperative Radiotherapy for Stage T3 Adenocarcinoma of Rectum”
trog trial
TROG trial
  • Commenced July 2001
  • Multicentre (17 so far)
  • More than 100 patients recruited
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