Abstract
Background:
Prostate-specific antigen (PSA) levels in midlife are strongly associated with the long-term risk of lethal prostate cancer in cohorts not subject to screening. This is the first study evaluating the association between PSA levels drawn as part of routine medical care in the Norwegian population and prostate cancer incidence and mortality.
Objective:
To determine the association between midlife PSA levels <4.0 ng/ml, drawn as part of routine medical care, and long-term risk of prostate cancer death.
Design, setting, and participants:
The Norwegian Prostate Cancer Consortium collected >8 million PSA results from >1 million Norwegian males ≥40 yr of age. We studied 176 099 men (predefined age strata: 40–54 and 55–69 yr) without a prior prostate cancer diagnosis who had a nonelevated baseline PSA level (<4.0 ng/ml) between January 1, 1995 and December 31, 2005.
Intervention:
Baseline PSA.
Outcome measurements and statistical analysis:
We assessed the 16-yr risk of prostate cancer mortality. We calculated the discrimination (C-index) between predefined PSA strata (<0.5, 0.5–0.9, 1.0–1.9, 2.0–2.9, and 3.0–3.9 ng/ml) and subsequent prostate cancer death. Survival curves were plotted using the Kaplan-Meier method.
Results and limitations:
The median follow-up time of men who did not get prostate cancer was 17.9 yr. Overall, 84% of men had a baseline PSA level of <2.0 ng/ml and 1346 men died from prostate cancer, with 712 deaths (53%) occurring in the 16% of men with the highest baseline PSA of 2.0–3.9 ng/ml. Baseline PSA levels were associated with prostate cancer mortality (C-index 0.72 for both age groups, 40–54 and 55–69 yr). The fact that the reason for any given PSA measurement remains unknown represents a limitation.
Conclusions:
We replicated prior studies that baseline PSA at age 40–69 yr can be used to stratify a man’s risk of dying from prostate cancer within the next 15–20 yr.
Patient summary:
A prostate-specific antigen level obtained as part of routine medical care is strongly associated with a man’s risk of dying from prostate cancer in the next two decades.
Keywords: Prostate cancer, Screening, Prostate-specific antigen
1. Introduction
Prostate-specific antigen (PSA) levels are strongly prognostic of the long-term risk of prostate cancer death in men without a diagnosis of prostate cancer [1–6]. Several groups have proposed using a “baseline” PSA value, taken at age 45–55 yr, to predict mortality and thus risk stratify screening. The European Association of Urology (EAU) suggests using baseline PSA levels as the first test of a screening algorithm for men aged 50–70 yr and with subsequent rescreening intervals adapted to a man’s age and PSA levels [7]. This algorithm was developed to ensure early diagnosis of clinically significant prostate cancer and to reduce overdiagnosis and overtreatment of insignificant prostate cancer: men with a PSA level of below 1 ng/ml should repeat their PSA testing after 5 yr when below age 60 yr and should stop PSA testing when older, whereas men with a PSA level of 1–3 ng/ml should be rescreened every 2–4 yr. Only men whose PSA level is above 3 ng/ml should undergo further evaluation potentially including prostate magnetic resonance imaging and prostate biopsy [7].
To date, all studies exploring the association between baseline PSA and the long-term risk of prostate cancer mortality have utilized PSA values measured retrospectively from archived blood samples. In two Swedish cohorts, one from the Malmö area and the other from Västerbotten, where PSA screening as well as opportunistic screening was virtually absent during the time of blood sampling, PSA was measured in a research laboratory many years after blood samples were deep-frozen. Baseline PSA was strongly associated with prostate cancer death in both cohorts, as expressed by a C-index between 0.80 and 0.90 [6,8]. In Norway, screening for prostate cancer is not recommended except for men with symptoms or signs of prostate cancer or a strong family history or a known genetic predisposition. However, the so-called “opportunistic screening” using the PSA test is common.
In this study, we obtained data from the Norwegian Prostate Cancer Consortium (NPCC), a consortium recently established to assess the impact of PSA testing in Norway. The aim of this study is to estimate the long-term risk of prostate cancer incidence and mortality among men aged 40–69 yr with baseline PSA values within the normal range (<4.0 ng/ml).
2. Patients and methods
2.1. Study population
The Regional Committee for Medical Research Ethics Southeast Norway approved collection of PSA test results from Norwegian health care laboratories and merging these results with information from public health registries, such as the Norwegian Cancer Registry, the Population Registry, and the Norwegian Cause of Death Registry. The laboratories provided PSA test results, including the sampling date and the National Identity Number (NIN), which is unique for all Norwegian residents. Data from the population registries were retrieved and merged by NIN with the PSA results.
To ensure data security, all data were transferred either directly via an encrypted link to the University of Oslo Services for sensitive data (TSD) server or by a code-protected memory device. The NPCC collected results from >8 million PSA measurements from >1 million Norwegian males, aged at least 40 yr.
The following inclusion criteria were used for this study: (1) men with a valid Norwegian NIN; (2) a baseline PSA, that is, the first registered PSA measurement in the NPCC database, between January 1, 1995 and December 31, 2005 (ensuring sufficient observation time); (3) no record of a prostate cancer diagnosis in the Norwegian Cancer Registry before the baseline PSA measurement; (4) age 40.0–69.9 yr at baseline PSA test (ie, a man’s first PSA value in the database); (5) for individuals >50 yr, screening of available laboratory data from the last 2 yr preceding the first PSA test for the absence of PSA analyses to ensure that the PSA value used for the analysis represented the man’s first PSA test, and not a follow-up test after previous PSA testing; and (6) a baseline PSA measurement of ≤3.99 ng/ml (as PSA values below 4.0 ng/ml were historically considered normal in Norway [9]).
The Norwegian Prostate Cancer Registry (NoPCR) was established in 2004 as a subregistry of the Cancer Registry of Norway. The NoPCR changed tumor grade recording from World Health Organization (WHO) grade to Gleason score as follows: WHO I → Gleason score 6, WHO II → Gleason score 7, and WHO III → Gleason score 8–10. Reporting of the extent of prostate cancer was gradually changed from the SEER-based categorization of “localized,” “regional,” or “metastatic” to the TNM classification. In this study, risk groups were defined as outlined in Table 1. Censoring for prostate cancer and death (from both all causes and prostate cancer) was done at the last date of complete records—December 31, 2020, on data obtained from the Cancer Registry and Population Registry between January and March 2022.
Table 1 –
Patient characteristics of men diagnosed with prostate cancer (n = 13 892)
| Clinical stage at diagnosis (n = 12 722), 1170 (8.4%) missing | ||
| SEER | Localized | 1064 (7.7%) |
| Regional | 163 (1.2%) | |
| Distant | 118 (0.8%) | |
| TNM | T1 | 4928 (39%) |
| T2 | 3523 (28%) | |
| T1-T2 (under active surveillance) | 46 (0.3%) | |
| T3 | 1591 (12%) | |
| T4 | 208 (1.6%) | |
| N1 | 515 (4.0%) | |
| M1 | 573 (4.5%) | |
| Gleason score at diagnosis (n = 13 230), missing 662 (4.8%) | ||
| 3 + 3 = 6 | 4539 (34%) | |
| 3 + 4 = 7a | 3581 (27%) | |
| 4 + 3 = 7b | 1919 (15%) | |
| 7 (not further specified) | 126 (1%) | |
| 8–10 | 3065 (23%) | |
| PSA at diagnosis (n = 13 892), ng/ml | ||
| <10 | 9775 (70%) | |
| 10–19 | 2787 (20%) | |
| 20–50 | 837 (6%) | |
| 50–100 | 225 (1.6%) | |
| >100 | 268 (1.9%) | |
| Risk group at diagnosis (based on PSA, Gleason, and TNM) a (n = 13 120), missing 772 (5.5%) | ||
| Low | 3282 (25%) | |
| Intermediate | 5076 (39%) | |
| High/locally advanced | 3985 (30%) | |
| Metastatic | 772 (6%) | |
PSA = prostate-specific antigen.
Low risk: Gleason score 6 and PSA <10 ng/ml and either SEER-based “localized” or T1–2, N0, M0; intermediate risk: Gleason 7 and/or PSA 10–20 ng/ml and/or and either SEER-based localized or T1–2, N0, M0; high risk/locally advanced: Gleason score 8–10 and/or PSA 20–100 ng/ml and/or either SEER-based regional or T3–4, and/or N0–1 and M0; metastatic: PSA >100 ng/ml or either SEER-based metastatic or M1 (any T or any N).
2.2. Population Registry and Norwegian Cause of Death Registry
The Norwegian Population Registry and the Norwegian Cause of Death Registry together provide continuous registration on current address, emigration/immigration status, and date and cause of death. The reported underlying cause of death is made available to the NoPCR, providing the basis for the population-based cancer outcomes. In this study, we had access to the following: date of the last follow-up for the individuals alive, date of emigration for emigrated individuals, and date and cause of death for deceased individuals. Causes of death were categorized as prostate cancer or other.
2.3. Statistical analysis
We predefined age groups of 40–54 and 55–69 yr, and the following PSA strata: <0.5, 0.5–<1.0, 1.0–<2.0, 2.0–<3.0, and 3.0–<4.0 ng/ml. Complete records up to December 31, 2020 from the Cancer Registry, Norwegian Population Registry, and Norwegian Cause of Death Registry were used for follow-up, resulting in a minimum 15 yr of observation. Survival was estimated using Kaplan-Meier for both prostate cancer incidence and mortality. Discrimination was calculated using Harrel’s C-index. R 4.2.1., with packages survival 3.2–13 and prodlim, was used for statistical analysis, and ggplot2 and survminer were used for graphical output.
3. Results
In total, 176 099 men fulfilled the inclusion criteria. The median follow-up for patients without prostate cancer was 17.9 yr (Q25 16.4 yr, Q75 19.9 yr). The characteristics of the sample are shown in Table 2. About half were aged in their 50s, and 84% of the men had a baseline PSA level of <2.0 ng/ml. During the 12 yr from 1995 through 2006, the annual number of men meeting the inclusion criteria increased from 2494 in 1995 (1.4% of the studied population) to a peak of 29 834 in 2004 (17% of the studied population), with 29 524 been included in 2005, the last year of the inclusion period. This represents an average increase of 40% per year. A total of 13 892 men were diagnosed with prostate cancer. Disease characteristics are reported in Table 1.
Table 2 –
Cohort characteristics (N = 176 099)
| Age at first blood draw (yr) | 55 (49, 61) | |
| Follow-up time for men who did not die from prostate cancer (yr) | 17.9 (16.5, 19.9) | |
| Year of first blood draw | ||
| 1995 | 2494 (1.4%) | |
| 1996 | 5019 (2.9%) | |
| 1997 | 5591 (3.2%) | |
| 1998 | 7836 (4.4%) | |
| 1999 | 9368 (5.3%) | |
| 2000 | 14 638 (8.3%) | |
| 2001 | 18 566 (10.5%) | |
| 2002 | 24 648 (14.0%) | |
| 2003 | 28 581 (16.2%) | |
| 2004 | 29 834 (16.9%) | |
| 2005 | 29 524 (16.8%) | |
| Age at first blood draw (yr) | ||
| 40–44 | 19 084 (10.8%) | |
| 45–49 | 30 876 (17.5%) | |
| 50–54 | 35 008 (19.9%) | |
| 55–59 | 38 254 (21.7%) | |
| 60–64 | 30 134 (17.1%) | |
| 65–69 | 22 743 (12.9%) | |
| PSA level at first blood draw (ng/ml) | 0.90 (0.60, 1.53) | |
| 0–0.49 | 28 295 (16.1%) | |
| 0.5–0.99 | 63 605 (36.1%) | |
| 1.0–1.49 | 36 422 (20.7%) | |
| 1.5–1.99 | 19 063 (10.8%) | |
| 2.0–2.49 | 11 881 (6.7%) | |
| 2.5–2.99 | 7482 (4.2%) | |
| 3.0–3.49 | 5530 (3.1%) | |
| 3.5–3.99 | 3821 (2.2%) | |
| PSA level by age group (ng/ml) | ||
| Age group | All ages | 0.9 (0.6, 1.5) |
| 40–44 | 0.7 (0.5, 1.0) | |
| 45–49 | 0.8 (0.5, 1.2) | |
| 50–54 | 0.9 (0.6, 1.4) | |
| 55–59 | 1.0 (0.6, 1.7) | |
| 60–64 | 1.2 (0.7, 2.0) | |
| 65–69 | 1.3 (0.8, 2.2) | |
PSA = prostate-specific antigen.
Numbers represent frequency and percentage or median and interquartile range.
A total of 1346 men were reported to have had prostate cancer as an underlying cause of death during the median follow-up time of 17.9 yr, with 712 of these deaths (53%) occurring in the 16% of men with a baseline PSA level between 2.0 and 3.9 ng/ml and 1117 of these deaths (83%) occurring in the 48% of men with a baseline PSA level between 1.0 and 3.9 ng/ml.
A man’s baseline PSA value was associated with subsequent prostate cancer incidence and mortality in both age groups (40–54 and 55–69 yr). The lower the baseline PSA, the lower the probability of a prostate cancer diagnosis within 16 yr (Table 3) and 20 yr (Fig. 1). Within each age group, the probability of being diagnosed with prostate cancer was more than ten-fold higher in the highest (3.0–3.9 ng/ml) versus the lowest baseline PSA stratum (<0.5 ng/ml; Table 3). The association between baseline PSA levels and the risk of subsequent prostate cancer death was statistically significant (p < 0.001; Table 3 and Fig. 1). The risk of prostate cancer death was more than ten-fold higher in men with a baseline PSA level of 3.0–3.9 ng/ml than in men with a PSA level of <0.5 ng/ml (Table 3).
Table 3 –
Probabilities of prostate cancer diagnosis and death by initial PSA level and age at first blood draw, at 16 yr of follow-up from blood draw
| Age at blood draw (yr) | PSA level (ng/ml) | Cumulative probability of a prostate cancer diagnosis at 16 yr, % (95% CI) | Cumulative probability of prostate cancer death at 16 yr, % (95% CI) | ||
|---|---|---|---|---|---|
| 40–49 | |||||
| <0.5 | 0.3 | (0.2–0.4) | 0.0 | (0.0–0.0) | |
| 0.5–0.9 | 1.3 | (1.1–1.4) | 0.0 | (0.0–0.1) | |
| 1.0–1.4 | 4.3 | (3.9–4.7) | 0.1 | (0.0–0.2) | |
| 1.5–1.9 | 9.0 | (8.0–10.0) | 0.2 | (0.1–0.4) | |
| 2.0–2.9 | 16.1 | (14.5–17.6) | 0.4 | (0.1–0.6) | |
| 3.0–3.9 | 17.7 | (14.6–20.6) | 0.6 | (0.0–1.3) | |
| 50–54 | |||||
| <0.5 | 0.8 | (0.5–1.0) | 0.1 | (0.0–0.2) | |
| 0.5–0.9 | 2.6 | (2.3–2.9) | 0.2 | (0.1–0.3) | |
| 1.0–1.4 | 7.6 | (6.9–8.2) | 0.2 | (0.1–0.3) | |
| 1.5–1.9 | 13.8 | (12.6–15.0) | 0.3 | (0.1–0.5) | |
| 2.0–2.9 | 19.4 | (17.9–20.9) | 0.7 | (0.4–1.1) | |
| 3.0–3.9 | 29.5 | (26.8–32.2) | 1.6 | (0.91–2.4) | |
| 55–59 | |||||
| <0.5 | 1.2 | (0.9–1.6) | 0.1 | (0.0–0.3) | |
| 0.5–0.9 | 3.7 | (3.3–4.0) | 0.2 | (0.2–0.3) | |
| 1.0–1.4 | 8.0 | (7.3–8.6) | 0.5 | (0.3–0.6) | |
| 1.5–1.9 | 15.0 | (14.0–16.2) | 0.80 | (0.5–1.0) | |
| 2.0–2.9 | 22.1 | (20.9–23.3) | 1.2 | (0.9–1.6) | |
| 3.0–3.9 | 30.3 | (28.2–32.2) | 2.0 | (1.4–2.6) | |
| 60–64 | |||||
| <0.5 | 1.6 | (1.1–2.1) | 0.2 | (0.0–0.4) | |
| 0.5–0.9 | 4.0 | (3.5–4.4) | 0.4 | (0.3–0.6) | |
| 1.0–1.4 | 7.8 | (7.1–8.6) | 0.6 | (0.3–0.8) | |
| 1.5–1.9 | 14.1 | (12.9–15.2) | 1.1 | (0.7–1.4) | |
| 2.0–2.9 | 20.0 | (18.7–21.2) | 2.0 | (1.6–2.5) | |
| 3.0–3.9 | 27.4 | (25.5–29.2) | 2.9 | (2.1–3.6) | |
| 65–69 | |||||
| <0.5 | 1.5 | (0.9–2.2) | 0.4 | (0.1–0.7) | |
| 0.5–0.9 | 3.6 | (3.0–4.1) | 0.7 | (0.4–1.0) | |
| 1.0–1.4 | 6.5 | (5.7–7.4) | 0.9 | (0.5–1.2) | |
| 1.5–1.9 | 10.6 | (9.3–11.8) | 1.4 | (0.9–1.8) | |
| 2.0–2.9 | 15.8 | (14.6–17.1) | 3.2 | (2.6–3.9) | |
| 3.0–3.9 | 22.0 | (20.2–23.8) | 5.6 | (4.5–6.6) | |
CI = confidence interval; PSA = prostate-specific antigen.
Fig. 1 –
Cumulative risk of prostate cancer diagnosis and death by baseline PSA level and age group. (A) Cumulative risk of prostate cancer diagnosis in men aged 40–54 yr based on predefined PSA strata. (B) Cumulative risk of prostate cancer diagnosis in men aged 55–69 yr based on predefined PSA strata. (C) Cumulative risk of prostate cancer death in men aged 40–54 yr based on predefined PSA strata. (D) Cumulative risk of prostate cancer death in men aged 55–69 yr based on predefined PSA strata. PSA = prostate-specific antigen.
The concordance index (Harrel’s C-index) was 0.771 for prostate cancer incidence and 0.807 for death from prostate cancer. The C-indices for death from prostate cancer were 0.746, 0.729, and 0.713 for each age group in decades (Table 4).
Table 4 –
Concordance index (Harrel’s C) for baseline PSA versus prostate cancer diagnosis and prostate cancer death at 16 yr of follow-up for men aged 40–69 yr at blood draw
| Age group | Harrel’s C | 95% CI |
|---|---|---|
| Prostate cancer diagnosis | ||
| 40–69 (all) | 0.771 | 0.768, 0.775 |
| 40–49 | 0.775 | 0.766, 0.785 |
| 50–59 | 0.754 | 0.748, 0.759 |
| 60–69 | 0.720 | 0.713, 0.726 |
| Prostate cancer death | ||
| 40–69 (all) | 0.807 | 0.796, 0.819 |
| 40–49 | 0.746 | 0.686, 0.806 |
| 50–59 | 0.729 | 0.704, 0.753 |
| 60–69 | 0.713 | 0.694, 0.733 |
CI = confidence interval; PSA = prostate-specific antigen.
4. Discussion
We studied the association between baseline PSA obtained as part of routine health care among men aged 40–69 yr and the risks of a subsequent prostate cancer diagnosis and prostate cancer death. We found that increased levels of PSA below normal biopsy thresholds (<4 ng/ml) were associated with an increased risk of both prostate cancer diagnosis and mortality. The risk of subsequent prostate cancer death varied considerably among men with an initial “normal” PSA level, defined as below 4 ng/ml, with 53% of prostate cancer deaths occurring in the 16% of men with a baseline PSA level between 2.00 and 3.99 ng/ml. Further, the 25-fold difference in the raw proportion of prostate cancer deaths between men with PSA <0.5 and 3.0–3.99 ng/ml highlights the huge differences among men with “normal” baseline PSA.
The NPCC study is based on PSA measurements from a total Norwegian population where PSA was measured for any cause, due to a clinical suspicion of cancer or as a part of a voluntary check-up, or due to the wish of the patient, but not as part of an organized PSA screening program.
In our study, we chose to analyze the risk of subsequent prostate cancer diagnosis or death in a normal range of PSA values (<4 ng/ml) that, at baseline, would generally not have generated a subsequent imaging or biopsy in Norway during the inclusion time of 1995–2005, to avoid an ascertainment bias resulting from men being referred for prostate biopsies when their PSA level was >4 ng/ml.
The Malmö Diet and Cancer cohort and the Västerbotten Intervention Project, on the contrary, represent the rare opportunity to correlate a midlife PSA level with the risk of subsequent death due to prostate cancer without interventions triggered by raised PSA values, as the data were collected retrospectively. Thereby, the reported association between baseline PSA and prostate cancer death was not perturbed by any interventions such that the Malmö Diet and Cancer cohort reported the C-indices of 0.86, 0.85, and 0.84 for all 11 506 unscreened men aged 45–73 yr, and those aged 50 and 60 yr, respectively [6,8]. Of a similar magnitude were the C-indices of 0.859 and 0.840 at age 50 and 60 yr, respectively, in the Västerbotten Intervention Project.
Overall, our findings were consistent with the Malmö and Västerbotten studies, with a weaker association between baseline PSA and prostate cancer death, but a stronger association with the incidence of prostate cancer. These findings are predictable based on the different settings of these studies. The association between PSA and prostate cancer diagnosis increases due to the ascertainment bias as the NPCC cohort comprises an unknown proportion of men undergoing opportunistic screening, as men with higher PSA are more likely to eventually meet biopsy thresholds and be subject to biopsy. Consequently, the association between PSA and prostate cancer mortality will be weakened in the NPCC cohort, as men with higher PSA are more likely to be subsequently treated and avoid death from cancer.
Our study complements others in highlighting the strong prognostic value of baseline PSA and supporting a risk-stratified screening algorithm based on age and PSA levels. The findings support the current EAU recommendation that men with lower PSA levels may undergo less frequent rescreening. The ongoing population-based screening trials ProsScreen, Gotenbrug-2, and PROBASE will, over the next several years, report the results of value for optimizing PSA thresholds and test intervals [10–12]. As we included only the men’s first PSA reading in the analysis, the results cannot be used for defining optimal screening intervals.
The strengths of our study include the large cohort size and the extensive coverage and accuracy of the Norwegian public registries. There are several limitations. First, the absolute estimates of prostate cancer incidence and mortality may not be applicable to populations of other ethnicities.
Second, our study did not account for differences in laboratory assay methods. Nevertheless, the predictive accuracy of a baseline PSA level was high and consistent with those of the Malmö, Västerbotten, and PLCO studies [6,8]. The use of PSA values obtained from clinical settings, as opposed to experimental settings, could be viewed both as a strength and as a weakness. Furthermore, the reassuringly high corroboration of previous studies implies that potential variations between local PSA laboratories are limited as these would have weakened the accuracy of our findings. Third, the clinical indications for a man’s PSA measurement are not known, and are likely a combination of screening PSA values and those measured for clinical indications such as a family history or the presence of lower urinary tract symptoms. Fourth, potential clinical decisions based on these PSA results are not known, and the clinical follow-up of the men and the impact of subsequent treatment of prostate cancer were not assessed. An assumed prostate cancer mortality reduction by more common opportunistic PSA testing in the USA, as hypothesized by Welch and Albertsen [13], might have caused or at least contributed to lower mortality rates as opposed to Scandinavia, such that the reported absolute risks of prostate cancer death observed in our study are applicable only to men in countries with prostate cancer mortality similar to that of Norway.
5. Conclusions
We replicated prior studies that a baseline PSA value at age 40–69 yr can be used to stratify a man’s risk of dying from prostate cancer within the next 15–20 yr and demonstrated the applicability of routinely measured PSA.
Supplementary Material
Acknowledgments:
We sincerely thank the Norwegian Prostate Cancer Patient Organization (PROFO) for supporting NPCC with its letter to laboratory managers and hospital directors to contribute to NPCC with their data. PROFO has also supported this study financially as did the EAU Research Foundation in the form of a seeding grant. Further, we are indebted to Fürst Laboratories for not only providing by far the most PSA measurements, but also allowing Johan Bjerner to contribute intellectually and practically with organizing NPCC and its database. Fürst has also provided financial support.
Funding/Support and role of the sponsor:
The work of Sigrid V. Carlsson and Hans Lilja on this paper was supported in by funding from the National Institutes of Health/National Cancer Institute (P30-CA008748) and K22-CA234400 to Sigrid V. Carlsson. Ola Bratt was funded by Region Västra Götaland (ALF).
Footnotes
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Financial disclosures:
Jan Oldenburg certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Hans Lilja holds patents on assays for intact PSA (Antibody, immunoassay and method for prostate cancer detection. US patent no. US 7,872,104 B2) and, with Andrew Vickers, a patent for a statistical method to detect prostate cancer (Methods and apparatuses for predicting risk of prostate cancer and prostate gland volume. US patent no. US. 9,672,329 B2) commercialized by OPKO Health. Drs. Hans Lilja and Andrew Vickers receive royalties from the sales of the test and have stock and stock options in OPKO Health. Jan Oldenburg reports receipt of grants/research supports from Bristol-Myers Squibb, Merck Sharp & Dome, Pfizer, and Roche; receipt of honoraria or consultation fees from Astellas, Astra Zeneca, Bayer, BMS, EISAI, Ipsen, Janssen-Cilag, and Roche; and participation in a company-sponsored speakers’ bureau of Astellas, Astra Zeneca, Bayer, and BMS. Sigrid V. Carlsson has received travel reimbursement from Ipsen. All other authors have no conflicts of interest to declare.
Among 40- to 70-yr-old men with a “normal” prostate-specific antigen (PSA) value (below 4 ng/ml) sampled in routine medical care, the risk of dying from prostate cancer in the next two decades is associated with the PSA level.
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