Establishment of reference intervals for serum [−2]proPSA (p2PSA), %p2PSA and prostate health index in healthy men

Figures & data

Table 1 Physical examination findings in the population of recruited patients

Examination Findings		Age groups (years)				Total
		<40	40–49	50–59	≥60
tPSA <4 ng/mL	n (%)	156 (10.28)	432 (28.48)	356 (23.47)	573 (37.77)	1517 (100)
Ultrasound results (−)	n (%)	135 (86.54)	306 (70.83)	166 (46.63)	125 (21.82)	732 (48.25)
Ultrasound results (+)	n (%)	21 (13.46)	126 (29.17)	190 (53.37)	448 (78.18)	785 (51.75)

Notes: Ultrasound results (−) defined as normal prostate size, without any positive manifestations including prostate nodules, bilateral asymmetry of the outer glands, increased blood flow signals in the glands, unclear boundaries between the inner and outer glands and abnormal morphology.

Abbreviation: tPSA, total prostate-specific antigen.

Figure 1 (A) Quantitative distribution of subjects in four different age groups. (B) Proportion of Ultrasound results (−) and Ultrasound results (+) subjects in four different age groups.

Notes: Ultrasound (−) defined as normal prostate size, without any positive manifestations including prostate nodules, bilateral asymmetry of the outer glands, increased blood flow signals in the glands, unclear boundaries between the inner and outer glands, abnormal morphology; Ultrasound (+) defined as oversize prostate, or with manifestations including inflammatory change, prostate nodules, bilateral asymmetry of the outer glands, increased blood flow signals in the glands, unclear boundaries between the inner and outer glands, abnormal morphology.

Abbreviation: tPSA, total prostate-specific antigen.

Table 2 Mean, standard deviation (SD) of the mean, and selected percentiles for PSA tests in healthy men of various ages

	Age group (year)	n	Mean (SD)	Percentiles
				5th	10th	25th	50th	75th	90th	95th
tPSA (ng/mL)	All ages	726	0.92 (0.60)	0.31	0.38	0.52	0.79	1.10	1.61	2.15
	<40	134	0.93 (0.62)	0.32	0.41	0.55	0.76	1.14	1.79	2.20
	40–49	305	0.92 (0.55)	0.33	0.41	0.56	0.80	1.10	1.53	2.02
	50–59	164	0.90 (0.57)	0.32	0.39	0.51	0.77	1.13	1.62	2.12
	≥60	123	0.94 (0.72)	0.20	0.27	0.44	0.78	1.10	1.83	2.88
	p-value	0.5856 (NS)
fPSA (ng/mL)	All ages	726	0.31 (0.17)	0.11	0.14	0.20	0.28	0.40	0.53	0.62
	<40	134	0.34 (0.15)	0.15	0.19	0.23	0.32	0.43	0.55	0.62
	40–49	305	0.32 (0.17)	0.12	0.15	0.20	0.28	0.39	0.52	0.62
	50–59	164	0.29 (0.17)	0.10	0.13	0.18	0.24	0.37	0.54	0.65
	≥60	123	0.30 (0.18)	0.08	0.10	0.16	0.27	0.40	0.53	0.62
	p-value	0.0009 (***)
%fPSA	All ages	726	0.38 (0.14)	0.17	0.21	0.28	0.36	0.47	0.56	0.64
	<40	134	0.43 (0.15)	0.18	0.22	0.31	0.43	0.53	0.64	0.70
	40–49	305	0.38 (0.13)	0.18	0.22	0.28	0.35	0.46	0.55	0.63
	50–59	164	0.35 (0.13)	0.16	0.20	0.26	0.33	0.45	0.53	0.58
	≥60	123	0.36 (0.13)	0.15	0.20	0.27	0.34	0.44	0.52	0.60
	p-value	<0.0001 (***)
p2PSA (pg/mL)	All ages	726	6.75 (4.20)	2.20	2.87	4.01	5.80	8.37	11.52	14.30
	<40	134	7.38 (4.59)	2.73	3.31	4.87	6.54	8.92	11.56	15.75
	40–49	305	7.21 (4.54)	2.40	3.18	4.10	6.12	9.07	12.17	16.65
	50–59	164	6.04 (3.57)	2.24	2.49	3.71	5.21	7.26	11.25	14.11
	≥60	123	5.84 (3.28)	1.79	2.16	3.39	5.33	7.70	10.29	12.79
	p-value	0.0001 (***)
%p2PSA	All ages	726	2.25 (1.07)	1.36	1.49	1.72	2.07	2.45	3.02	3.60
	<40	134	2.17 (0.88)	1.31	1.50	1.71	1.97	2.39	2.67	3.71
	40–49	305	2.37 (1.32)	1.42	1.56	1.81	2.10	2.51	3.21	3.92
	50–59	164	2.17 (0.85)	1.40	1.47	1.67	2.03	2.44	2.94	3.20
	≥60	123	2.15 (0.74)	1.24	1.36	1.58	2.09	2.53	3.27	3.44
	p-value	0.0730 (NS)
phi	All ages	726	20.28 (10.41)	10.37	11.63	14.52	18.46	23.07	28.82	35.86
	<40	134	19.95 (9.66)	10.37	11.00	13.72	17.77	22.36	30.90	36.56
	40–49	305	21.68 (12.86)	11.19	12.59	15.17	19.51	23.69	30.45	39.83
	50–59	164	19.15 (7.05)	10.70	11.70	14.34	17.20	22.99	27.75	31.08
	≥60	123	18.66 (7.35)	8.66	10.19	13.65	16.95	22.83	26.80	32.55
	p-value	0.0491 (*)

Notes: NS indicates no significance; *indicates p<0.05; ***indicates p<0.001.

Abbreviations: tPSA, total prostate-specific antigen; fPSA, free prostate-specific antigen; p2PSA, [−2]proPSA; phi, prostate health index; NS, not significant.

Figure 2 Serum levels of (A) tPSA, (B) fPSA, (C) %fPSA, (D) p2PSA, (E) %p2PSA and (F) phi in healthy males among the four different age groups. Boxes and horizontal lines indicate interquartile ranges and medians, respectively; whiskers stretch from the 2.5th to 97.5th percentiles for each age group.Notes: *indicates p<0.05; **indicates p<0.01; ***indicates p<0.001.

Abbreviations: tPSA, total prostate-specific antigen; fPSA, free prostate-specific antigen; p2PSA, [−2]proPSA; phi, prostate health index.

Figure 3 The age-related distribution curves of PSA (A), p2PSA and phi (B). Dots, squares and triangles indicate medians, respectively; whiskers stretch from the −95% confidence interval (CI) to the 95% CI for each age group.

Abbreviations: tPSA, total prostate-specific antigen; fPSA, free prostate-specific antigen; p2PSA, [−2]proPSA; phi, prostate health index.

Table 3 Reference intervals for p2PSA, % p2PSA and phi

Biomarker	Age group (years)	n	Percentile
			2.5th	97.5th
p2PSA (pg/mL)	All ages	726	1.88 (1.72–2.07)	17.40 (15.83–18.81)
	<40	134	2.02 (1.60–2.89)	17.93 (15.17–37.58)
	40–49	305	2.08 (1.74–2.34)	19.02 (17.22–25.70)*
	50–59	164	1.60 (1.41–2.25)	15.75 (14.00–19.71)
	≥60	123	1.28 (0.28–1.81)	15.15 (11.85–16.57)*
%p2PSA	All ages	726	1.26 (1.21–1.33)	4.54 (3.94–4.77)
	<40	134	1.17 (1.14–1.34)	4.69 (3.52–8.17)
	40–49	305	1.34 (1.29–1.39)*	4.82 (4.12–10.33)
	50–59	164	1.35 (1.15–1.41)	3.91 (3.18–8.56)
	≥60	123	1.21 (0.89–1.26)*	4.41 (3.41–5.09)
phi	All ages	726	9.48 (8.92–10.09)	45.50 (40.01–52.84)
	<40	134	9.77 (7.25–10.44)	48.44 (34.96–74.88)
	40–49	305	9.85 (9.00–10.98)*	65.28 (45.50–92.38)*
	50–59	164	9.98 (8.89–10.86)	39.72 (30.91–53.09)
	≥60	123	8.16 (6.26–8.92)*	40.76 (30.40–43.52)*

Notes: Values in brackets indicate the 90% confidence interval (CI) of the corresponding reference limits. *Indicates non-overlapping 90% CIs between the two groups.

Abbreviations: p2PSA, [−2]proPSA; phi, prostate health index.