Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

ASTEC study group, H Kitchener, A M C Swart, Q Qian, C Amos, M K B Parmar, C Amos, P Blake, A Branson, C H Buckley, C W E Redman, J Shepherd, G Dunn, P Heintz, J Yarnold, P Johnson, M Mason, R Rudd, P Badman, S Begum, N Chadwick, S Collins, K Goodall, J Jenkins, K Law, P Mook, J Sandercock, C Goldstein, B Uscinska, M Cruickshank, D E Parkin, R A F Crawford, J Latimer, M Michel, J Clarke, S Dobbs, R J McClelland, J H Price, K K Chan, C Mann, R Rand, A Fish, M Lamb, C Goodfellow, S Tahir, J R Smith, R Gornall, R Kerr-Wilson, G R Swingler, B A Lavery, K K Chan, S Kehoe, A Flavin, J Eddy, J Davies-Humphries, M Hocking, L J Sant-Cassia, S Pearson, R L Chapman, J Hodgkins, I Scott, D Guthrie, M Persic, F N Daniel, D Yiannakis, M I Alloub, L Gilbert, M R Heslip, A Nordin, G Smart, V Cowie, M Katesmark, P Murray, J Eddy, R Gornall, G R Swingler, C B Finn, M Moloney, A Farthing, J Hanoch, P W Mason, A McIndoe, W P Soutter, H Tebbutt, J S Morgan, D Vasey, D J Cruickshank, J Nevin, S Kehoe, I Z McKenzie, C Gie, Q Davies, D Ireland, P Kirwan, Q Davies, M Lamb, R Kingston, J Kirwan, J Herod, A Fiander, K Lim, A C Head, C B Lynch, A J Browning, C Cox, D Murphy, I D Duncan, C Mckenzie, S Crocker, J Nieto, M E L Paterson, J Tidy, A Duncan, S Chan, K M Williamson, A Weekes, O A Adeyemi, R Henry, V Laurence, S Dean, D Poole, M J Lind, R Dealey, K Godfrey, M M Hatem, A Lopes, J M Monaghan, R Naik, J Evans, A Gillespie, M E L Paterson, J Tidy, T Ind, J Lane, S Oates, D Redford, M Ford, A Fish, P Larsen-Disney, N Johnson, A Bolger, P Keating, P Martin-Hirsch, L Richardson, J B Murdoch, A Jeyarajah, M Lamb, N McWhinney, A Farthing, P W Mason, H Kitchener, J L Beynon, P Hogston, E M Low, R Woolas, R Anderson, J B Murdoch, P A R Niven, R Kerr-Wilson, K Chin, P Flynn, O Freites, G H Newman, O McNally, J Cullimore, A Olaitan, T Mould, V Menon, C W E Redman, M George, M H Hatem, A Evans, A Fiander, R Howells, K Lim, G Cawdell, A P Warwick, D Eustace, J Giles, S Leeson, J Nevin, A L van Wijk, K Karolewski, M Klimek, P Blecharz, D McConnell, ASTEC study group, H Kitchener, A M C Swart, Q Qian, C Amos, M K B Parmar, C Amos, P Blake, A Branson, C H Buckley, C W E Redman, J Shepherd, G Dunn, P Heintz, J Yarnold, P Johnson, M Mason, R Rudd, P Badman, S Begum, N Chadwick, S Collins, K Goodall, J Jenkins, K Law, P Mook, J Sandercock, C Goldstein, B Uscinska, M Cruickshank, D E Parkin, R A F Crawford, J Latimer, M Michel, J Clarke, S Dobbs, R J McClelland, J H Price, K K Chan, C Mann, R Rand, A Fish, M Lamb, C Goodfellow, S Tahir, J R Smith, R Gornall, R Kerr-Wilson, G R Swingler, B A Lavery, K K Chan, S Kehoe, A Flavin, J Eddy, J Davies-Humphries, M Hocking, L J Sant-Cassia, S Pearson, R L Chapman, J Hodgkins, I Scott, D Guthrie, M Persic, F N Daniel, D Yiannakis, M I Alloub, L Gilbert, M R Heslip, A Nordin, G Smart, V Cowie, M Katesmark, P Murray, J Eddy, R Gornall, G R Swingler, C B Finn, M Moloney, A Farthing, J Hanoch, P W Mason, A McIndoe, W P Soutter, H Tebbutt, J S Morgan, D Vasey, D J Cruickshank, J Nevin, S Kehoe, I Z McKenzie, C Gie, Q Davies, D Ireland, P Kirwan, Q Davies, M Lamb, R Kingston, J Kirwan, J Herod, A Fiander, K Lim, A C Head, C B Lynch, A J Browning, C Cox, D Murphy, I D Duncan, C Mckenzie, S Crocker, J Nieto, M E L Paterson, J Tidy, A Duncan, S Chan, K M Williamson, A Weekes, O A Adeyemi, R Henry, V Laurence, S Dean, D Poole, M J Lind, R Dealey, K Godfrey, M M Hatem, A Lopes, J M Monaghan, R Naik, J Evans, A Gillespie, M E L Paterson, J Tidy, T Ind, J Lane, S Oates, D Redford, M Ford, A Fish, P Larsen-Disney, N Johnson, A Bolger, P Keating, P Martin-Hirsch, L Richardson, J B Murdoch, A Jeyarajah, M Lamb, N McWhinney, A Farthing, P W Mason, H Kitchener, J L Beynon, P Hogston, E M Low, R Woolas, R Anderson, J B Murdoch, P A R Niven, R Kerr-Wilson, K Chin, P Flynn, O Freites, G H Newman, O McNally, J Cullimore, A Olaitan, T Mould, V Menon, C W E Redman, M George, M H Hatem, A Evans, A Fiander, R Howells, K Lim, G Cawdell, A P Warwick, D Eustace, J Giles, S Leeson, J Nevin, A L van Wijk, K Karolewski, M Klimek, P Blecharz, D McConnell

Abstract

Background: Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer.

Methods: From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884.

Findings: After a median follow-up of 37 months (IQR 24-58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1.16 (95% CI 0.87-1.54; p=0.31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI -4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1.35 (1.06-1.73; p=0.017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1-12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1.04 (0.74-1.45; p=0.83) and for recurrence-free survival was 1.25 (0.93-1.66; p=0.14).

Interpretation: Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials.

Figures

Figure 1
Figure 1
ASTEC trial design
Figure 2
Figure 2
Profile of ASTEC surgical trial We did not collect logs of patients assessed for eligibility. TAH=total abdominal hysterectomy. BSO=bilateral salpingo-oophorectomy. H=hysterectomy.
Figure 3
Figure 3
Overall survival (A), disease and treatment-related deaths (B), and recurrence-free survival (C) by treatment group
Figure 4
Figure 4
Kaplan-Meier plots for the two treatment groups for overall and recurrence-free survival together with the model curves from fitting the Royston-Parmar parametric model A and B show Kaplan-Meier estimates, with Royston-Parmar parametric model fitted. C and D show the absolute difference over time (95% CI) in survival from Royston-Parmar parametric model.
Figure 5
Figure 5
Effect of lymphadenectomy on overall survival (A) and recurrence-free survival (B) in women in different risk groups of recurrence O–E=observed minus expected. Outer bars show 99% CI, inner bars show 95% CI.

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