Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and Gleason Grade: Nationwide, population-based register study

Abstract

The objective was to investigate the proportion of men with metastatic prostate cancer in groups defined by T stage, Gleason Grade Group (GGG) and serum levels of prostate-specific antigen (PSA) and if PSA can be used to rule in metastatic prostate cancer when combined with T stage and GGG. We identified 102,076 men in Prostate Cancer data Base Sweden 4.0 who were diagnosed with prostate cancer in 2006-2016. Risk of metastases was assessed for PSA stratified on T stage and five-tiered GGG. For men who had not undergone bone imaging, we used multiple imputation to classify metastatic prostate cancer. Advanced T stage, high GGG and high PSA were related to bone metastases. For example: only 79/38 190 (0.2%) of men with T1-2 and GGG 1 had PSA above 500 ng/mL, and 29/79 (44%) of these men had metastases; whereas 1 154/7 018 (16%) of men with T3-4 and GGG 5 had PSA above 500 ng/ml and 1 088/1 154 (94%) of these men had metastases. However, no PSA cutoff could accurately identify the majority of men with metastatic prostate cancer (i.e. high sensitivity) while also correctly classifying most men without metastasis (i.e. high specificity). In conclusion, these results support the use of imaging to confirm bone metastases in men with advanced prostate cancer as no PSA level in combination with T stage and GGG could accurately rule in metastatic prostate cancer and thereby safely omit bone imaging.

Simulation model of disease incidence driven by diagnostic activity

“…We used a modified version of the National Comprehensive Cancer Network 5‐tiered risk categorization, previously described in Reference 19. Recent findings 36,37 have indicated that a PSA cut‐off of 100 ng/mL is suboptimal for indicating metastatic disease, and therefore we defined distant metastases as either M stage M1 or PSA ≥ 500 ng/mL. Consequently, regionally metastatic is defined as either T stage T4 or N stage N1 or PSA between 50 and 500 ng/mL.…”

“…Data was considered missing at random (MAR) apart from M stage which was imputed using logistic regression but with a modified algorithm to model a nonignorable missing data mechanism 41 . A similar imputation model has previously been used and described in 37,42 …”

The power of empirical data; lessons from the clinical registry initiatives in Scandinavian cancer care

“…Optimal management of early-stage tumors is an area of debate where the registries have provided relevant data on favorable results in early-stage renal cell cancer and the use of transanal endoscopic microsurgery in T1 rectal cancer [28,48]. Clinical registry data can also be applied to build prediction models based on complex clinical information such as consultations, imaging, biomarkers and tumor data, to define patient groups that can be spared adjuvant treatment or need of intensified surveillance and/or rehabilitation [49][50][51][52][53][54][55]. The similararities in registry structures allow for pooling of data sets to reach sufficient power with a recent example from colon cancer, where the impact from anastomotic leaks was studied in close to 23,000 patients from Denmark, Norway and Sweden with anastomotic leaks in 3.7% and an adverse effect on survival in stage III tumors [56].…”

Isolated Solitary Lung Nodule in a Patient With Idiopathic Pulmonary Fibrosis and Concomitant Prostate Cancer: A Challenging Diagnosis

“…Prostate cancer (PCa), which is the most common cancer diagnosed in men worldwide [ 4 ], can often metastasize with an elevated rate in patients with increased T-stage, histopathological Gleason score, and prostate-specific antigen (PSA) [ 5 ]. Emergence of new radiological techniques such as positron emission tomography (PET) with prostate-specific membrane antigen (PSMA), using the gadolinium-68 radiotracer, has widely changed the definition of metastatic disease [ 6 ].…”