Central pathology review in multicenter trials and studies: lessons from the nephroblastoma trials.

BACKGROUND: : Central pathology review (CPR) is an important component of multicenter tumor trials. The authors retrospectively analyzed the quality of pathology material submitted to determine the benefits and limitations of rapid CPR.
METHODS: : Analysis of pathology specimens from previous renal tumors in children trials (1980-2007) included the number of cases submitted, the number of slides per case, discrepancies in diagnosis and staging between institutional pathologists and CPR, and the impact of rapid CPR on treatment.
RESULTS: : The percentage of cases submitted for CPR increased from 76% in earlier trials to 100% in the current trial. The number of slides submitted rose from a median of 6 (International Pediatric Oncology Society [SIOP] 9301) to 25 for the SIOP-UK Renal Tumors 2001 trial. Discrepancies between the institutional pathologists and CPR were as follows: diagnosis: SIOP 9, 17%; SIOP 93-01, 14%; United Kingdom Wilms Tumour 3 Trial (UKWT3), 3.5%; SIOP-UK 2001, 3.8%; staging: SIOP 6, 9%; SIOP 93-01, 14%; UKWT3, 17%; SIOP-UK 2001, 3.8% of cases. There were clinically significant discrepancies in diagnosis and/or stage in 30 of 152 (20%) cases submitted for delayed CPR in SIOP-UK 2001.
CONCLUSIONS: : The number and quality of material submitted for CPR has markedly improved over time, predominantly due to the introduction of a simple standard operating procedure. Discrepancies in diagnosis and staging remain, but rapid review CPR allows clinicians to modify treatment if required. Benefits from the CPR system followed in SIOP-UK 2001 have been clearly demonstrated, and similar systems should be considered for future trials of other tumors. Cancer 2009. (c) 2009 American Cancer Society.