The Cambridge Prognostic Groups for improved prediction of disease mortality at diagnosis in primary non-metastatic prostate cancer: a validation study

Abstract

BackgroundThe purpose of this study is to validate a new five-tiered prognostic classification system to better discriminate cancer-specific mortality in men diagnosed with primary non-metastatic prostate cancer.MethodsWe applied a recently described five-strata model, the Cambridge Prognostic Groups (CPGs 1-5), in two international cohorts and tested prognostic performance against the current standard three-strata classification of low-, intermediate- or high-risk disease. Diagnostic clinico-pathological data for men obtained from the Prostate Cancer data Base Sweden (PCBaSe) and the Singapore Health Study were used. The main outcome measure was prostate cancer mortality (PCM) stratified by age group and treatment modality.ResultsThe PCBaSe cohort included 72,337 men, of whom 7162 died of prostate cancer. The CPG model successfully classified men with different risks of PCM with competing risk regression confirming significant intergroup distinction (p < 0.0001). The CPGs were significantly better at stratified prediction of PCM compared to the current three-tiered system (concordance index (C-index) 0.81 vs. 0.77, p < 0.0001). This superiority was maintained for every age group division (p < 0.0001). Also in the ethnically different Singapore cohort of 2550 men with 142 prostate cancer deaths, the CPG model outperformed the three strata categories (C-index 0.79 vs. 0.76, p < 0.0001). The model also retained superior prognostic discrimination in the treatment sub-groups: radical prostatectomy (n = 20,586), C-index 0.77 vs. 074; radiotherapy (n = 11,872), C-index 0.73 vs. 0.69; and conservative management (n = 14,950), C-index 0.74 vs. 0.73. The CPG groups that sub-divided the old intermediate-risk (CPG2 vs. CPG3) and high-risk categories (CPG4 vs. CPG5) significantly discriminated PCM outcomes after radical therapy or conservative management (p < 0.0001).ConclusionsThis validation study of nearly 75,000 men confirms that the CPG five-tiered prognostic model has superior discrimination compared to the three-tiered model in predicting prostate cancer death across different age and treatment groups. Crucially, it identifies distinct sub-groups of men within the old intermediate-risk and high-risk criteria who have very different prognostic outcomes. We therefore propose adoption of the CPG model as a simple-to-use but more accurate prognostic stratification tool to help guide management for men with newly diagnosed prostate cancer.Electronic supplementary materialThe online version of this article (10.1186/s12916-018-1019-5) contains supplementary material, which is available to authorized users.

Using prognosis to guide inclusion criteria, define standardised endpoints and stratify follow‐up in active surveillance for prostate cancer

“…However, guidelines on risk‐based management never only use Grade as a criterion and always use a composite of PSA, Grade, and Stage (AUA, National Comprehensive Cancer Network [NCCN], EAU, NICE). Moreover, we have previously seen in our two reports on the CPG model development and validation that men with GG2 and a high PSA level have similar outcomes to men with GG3 and a low PSA level . For these reasons, we feel that it is the composite score that is most relevant to clinical practice and AS management.…”

“…Our recent work has explored the innate heterogeneity within the traditional intermediate‐risk classification and shown two distinct sub‐groups with very different mortality and metastatic risks . In the present study, we put this sub‐classification to the test by comparing PCM in men managed by either immediate radical therapy or conservative means.…”

“…The Cambridge Prognostic Group (CPG) five-strata model has been tested in >86 000 men and consistently outperformed the National Institute for Health and Care Excellence (NICE)/European Association of Urology (EAU) prognostic model, regardless of treatment type and patient age [9]. In this model, we identified a sub-stratum of intermediate-risk cancer with low rates of PCM (CPG2) and a group with more lethal outcomes (CPG3) [8,9]. These subgroups correspond to the subsequently updated 2017 risk model revisions endorsed by the AUA/American Society for Therapeutic Radiology and Oncology (ASTRO)/Soci et e Internationale d'Urologie (SIU) guidelines, and designated as 'favourable' and 'unfavourable' intermediate-risk, respectively [10].…”

Using prognosis to guide early detection and treatment selection in non‐metastatic prostate cancer

“…the new AUA/American Society for Therapeutic Radiology and Oncology [ASTRO]/Society of Urologic Oncology [SUO] Prostate Cancer Guidelines). Large cohort studies have further confirmed that such sub‐stratification can indeed separate ‘intermediate‐risk’ men into good‐ and poor‐survival groups in terms of cancer mortality . An interesting question then arises as to what then actually constitutes ‘clinically significant’ or lethal disease.…”

“…Over recent years there has been an increasing awareness that our ideas on the lethality of primary non‐metastatic prostate cancer may need to change. This concept has emerged from a number of different sources including randomised controlled trials, reports from mature active surveillance programmes, and prognostic modelling work in large populations . The evidence suggests that for many men without metastatic disease (85% of all presentations from the recent UK National Prostate Cancer Audit) tumours will evolve slowly and will not translate into cancer‐related mortality, at least, not within the first 10–15 years of its natural history.…”