Development and validation of a novel risk score for the detection of insignificant prostate cancer in unscreened patient cohorts

Lorenzo Dutto,Christian Wagner,Gregory L Shaw,Andreas Schuette,Joern H Witt,John D Kelly,Ashwin Sridhar,Amar Ahmad,Timothy P Briggs,Senthil Nathan,Katerina Urbanova,Mustafa Addali

doi:10.1038/s41416-018-0316-2

Abstract

BackgroundActive surveillance is recommended for insignificant prostate cancer (PCa). Tools exist to identify suitable candidates using clinical variables. We aimed to develop and validate a novel risk score (NRS) predicting which patients are harbouring insignificant PCa.MethodsWe used prospectively collected data from 8040 consecutive unscreened patients who underwent radical prostatectomy between 2006 and 2016. Of these, data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition3: Gleason 3 + 3 only, index tumour volume < 1.3 cm3 and total tumour volume < 2.5 cm3). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). We compared the accuracy of existing predictive tools and the NRS in these cohorts.ResultsThe NRS (incorporating PSA, prostate volume, age, clinical T Stage, percent and number of positive biopsy cores) outperformed pre-existing predictive tools in derivation and validation cohorts (AUC 0.755 and 0.76, respectively). Selection bias due to analysis of a surgical cohort is acknowledged.ConclusionsThe advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making.

Highlights

Insignificant prostate cancer (PCa) can be defined as a cancer, which will not affect the patient during the natural course of his lifetime.[1]
All six preoperative clinical variables were statistically significant in a multivariate logistic model with insignificant PCa = 1 and significant PCa = 0 (Table 2)
The novel risk score (NRS) was developed as the weighted sum of the clinical variables in the multivariate model; where the weights are the shrunken regression coefficients via the penalised maximum likelihood of the elastic-net regularisation: NRS = −1.227*log(1 + PSA) + 0.022*trans-rectal ultrasound (TRUS) − 0.050*Age − 0.301*Stage − 0.016* PPC − 0.08*number of positive cores (NPC)

Summary

Introduction

Insignificant prostate cancer (PCa) can be defined as a cancer, which will not affect the patient during the natural course of his lifetime.[1]. Data from 2799 patients with Gleason 3 + 3 on biopsy were used to develop a multivariate model predicting the presence of insignificant PC at radical prostatectomy (ERSPC updated definition[3]: Gleason 3 + 3 only, index tumour volume < 1.3 cm[3] and total tumour volume < 2.5 cm[3]). This was used to develop a novel risk score (NRS) which was validated in an equivalent independent cohort (n = 441). CONCLUSIONS: The advantage of the NRS is that it can be tailored to patient characteristics and may prove to be valuable tool in clinical decision-making

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Discussion

Conclusion