Influence of serum total cholesterol, LDL, HDL, and triglyceride on prostate cancer recurrence after radical prostatectomy

Figures & data

Figure 1 Flow diagram of literature search process. PubMed database was comprehensively searched for potentially relevant studies through January 2019. A total of 156 potentially eligible studies were identified and 12 eligible studies were finally included in this meta-analysis.

Table 1 Main characteristics of the included studies

Author	Year	Region	Design	Follow-up (months)	No. of cases	Age (years)	Exposure (no.)	Rate of recurrence
Allott et al (black)^Citation9	2016	USA	R	Median: 32.4	628	Mean: 59.7 (SD: 6.4)	TC (46), LDL (46), HDL (188), TG (92)	181 (29%)
Allott et al (non-black)^Citation9	2016	USA	R	Median: 36	1020	Mean: 62.3 (SD: 5.8)	TC (69), LDL (88), HDL (433), TG (182)	272 (27%)
Allott et al^Citation23	2018	USA	P	Median: 45.6	669	Range: 40–79	TC (425)	138 (21%)
Bhindi et al^Citation24	2016	Canada	P	Median: 31	1939	Mean: 61.5 (SD: 6.9)	HDL (NR), TG (NR)	NR
Kang et al^Citation13	2015	Korea	R	Median: 21	663	Median: 68 (IQR: 62–72)	TG (109)	66 (10%)
Komaru et al^Citation12	2010	Japan	R	Median: 35	173	Median: 65 (SD: 5.1)	TC (NR)	NR
Macleod et al^Citation10	2015	USA	R	Median: 41	1706	NR	LDL (440), HDL (1174), TG (736)	279 (16%)
Ohno et al^Citation17	2016	Japan	R	Mean: 54.0	562	Mean: 65.9 (SD: 6.4)	TC (209)	168 (30%)
Post et al^Citation26	2011	USA	R	Median: 49	383	Mean: 60.9	HDL (86), TG (159)	67 (17%)
Rantaniemi et al^Citation14	2018	Finland	P	Median: 134.4	1314	Median: 64/62	TC (275), LDL (188), HDL (48), TG (145)	435 (33%)
Sanchís-Bonet et al^Citation11	2015	Spain	R	NR	1319	Mean: 66 (SD: 7.1)	HDL (449), TG (317)	NR
Shiota et al^Citation25	2014	Japan	R	Median: 14.8	283	Median: 65 (range: 49–78)	TC (NR), TG (NR)	49 (17%)
Wettstein et al^Citation15	2017	Switzerland	P	Median: 28	319	Median: 63 (range: 41–78)	TC (211), LDL (188), HDL (38), TG (117)	49 (15%)

Abbreviations: R, retrospective; P, prospective; no., number; IQR, inter-quartile range; SD, standard deviation; TC, total cholesterol; LDL, low-density lipoprotein; HDL, high-density lipoprotein; TG, triglyceride; NR, not reported.

Figure 2 A forest plot of hazard ratio for total cholesterol, which was reported in 7 studies (8 data sets).

Figure 3 A forest plot of hazard ratio for low-density lipoprotein (LDL), which was reported in 4 studies (5 data sets).

Figure 4 A forest plot of hazard ratio for high-density lipoprotein (HDL), which was reported in 7 studies (8 data sets).

Figure 5 A forest plot of hazard ratio for triglyceride, which was reported in 9 studies (10 data sets).

Table 2 Subgroup analyses stratified by study design and region

	Total cholesterol			Low-density lipoprotein			High-density lipoprotein			Triglyceride
N^a	HR (95% CI)	Pfor interaction	N^a	HR (95% CI)	Pfor interaction	N^a	HR (95% CI)	Pfor interaction	N^a	HR (95% CI)	Pfor interaction
Overall	7	0.92 (0.73–1.16)		4	0.87 (0.56–1.35)		7	1.09 (0.92–1.30)		9	1.01 (0.78–1.31)
Study design			0.160			0.025			0.494			0.051
Prospective	2	0.72 (0.56–0.91)		2	0.50 (0.34–0.73)		3	1.21 (0.95–1.54)		3	0.72 (0.58–0.90)
Retrospective	5	1.09 (0.79–1.51)		2	1.26 (1.03–1.56)		4	1.03 (0.80–1.32)		6	1.19 (0.91–1.57)
Geographical region			0.321			0.025			0.630			0.423
North America	2	1.27 (0.68–2.35)		2	1.26 (1.03–1.56)		4	1.09 (0.85–1.39)		4	1.07 (0.77–1.50)
Europe	2	0.87 (0.64–1.18)		2	0.50 (0.34–0.73)		3	1.10 (0.70–1.80)		3	0.98 (0.67–1.44)
Asia	3	0.65 (0.47–0.91)		0	-		0	-		2	0.63 (0.07–5.67)

Note: ^aThe number of studies included.

Abbreviations: HR, hazard ratio; CI, confidence interval.

Table 3 P-values of Begg’s test and Egger’s test

	Total cholesterol	Low-density lipoprotein	High-density lipoprotein	Triglyceride
Begg’s test	0.902	0.462	0.035	1.000
Egger’s test	0.943	0.203	0.029	0.903

Figure 6 Sensitivity analysis was conducted by excluding each study sequentially and then repeating the meta-analysis to determine the influence of a single study.

Figure 7 Begg’s funnel plots for publication bias. If publication bias is present, the plot will be asymmetrical.

Table S1  Newcastle–Ottawa Scale scores of each included study

Study^a	Representativeness of the cohort	Selection of the unexposed cohort	Ascertainment of exposure	Outcome of interest not present at start	Comparability^b	Outcome assessment	Enough follow-up^c	Adequacy of follow-up^d	Total scores
Allott et al (2016)^Citation9	*	*	*	*	**	*	*	*	9
Allott et al (2018)^Citation23	*	*	*	*	*	*	*	*	8
Bhindi et al (2016)^Citation24	*	*	*	*	**	*	*	*	9
Kang et al (2015)^Citation13	*	*	*	*	*	*	-	*	7
Komaru et al (2010)^Citation12	*	*	*	*	-	*	*	*	7
Macleod et al (2015)^Citation10	*	*	*	*	**	*	*	*	9
Ohno et al (2016)^Citation17	*	*	*	*	-	*	*	*	7
Post et al (2011)^Citation26	*	*	*	*	**	*	*	*	9
Rantaniemi et al (2018)^Citation14	*	*	*	*	**	*	*	*	9
Sanchís-Bonet et al (2015)^Citation11	*	*	*	*	-	*	-	*	6
Shiota et al (2014)^Citation25	*	*	*	*	-	*	-	*	6
Wettstein et al (2017)^Citation15	*	*	*	*	-	*	*	*	7

Notes: ^aA study can be awarded a maximum of one star for each item except the item ‘Comparability’. ^bA maximum of two stars can be awarded for this item. ^cA cohort study with a follow-up time more than 24 months was assigned one star. ^dA cohort study with a follow-up rate more than 75% was assigned one star.

Table S2 Subgroup analyses stratified by duration of follow-up, No. of patients, and NOS score

	Total cholesterol		Low-density lipoprotein		High-density lipoprotein		Triglyceride
N^a	HR (95% CI)	N^a	HR (95% CI)	N^a	HR (95% CI)	N^a	HR (95% CI)
Follow-up
≥ 36 months	4	0.78 (0.64–0.96)	3	0.96 (0.58–1.58)	4	0.97 (0.67–1.39)	4	1.06 (0.88–1.27)
<36 months	4	1.10 (0.65–1.85)	2	0.74 (0.26–2.08)	3	1.19 (0.95–1.49)	5	0.85 (0.45–1.59)
No. of patients
≥ 1000	2	0.88 (0.53–1.48)	3	0.96 (0.58–1.58)	5	1.19 (1.01–1.41)	5	0.98 (0.74–1.29)
<1000	6	0.93 (0.70–1.24)	2	0.74 (0.26–2.08)	3	0.80 (0.51–1.24)	5	1.00 (0.57–1.75)
NOS score
≥ 7	7	0.91 (0.72–1.16)	5	0.87 (0.56–1.35)	7	1.07 (0.88–1.32)	8	0.96 (0.72–1.27)
<7	1	1.05 (0.24–4.51)	0	-	1	1.10 (0.69–1.76)	2	1.44 (0.88–2.34)

Note: ^aThe number of data sets included.

Abbreviations: No., number; NOS, Newcastle–Ottawa Scale; HR, hazard ratio; CI, confidence interval.

Allott EH, Howard LE, Aronson WJ, et al. Racial differences in the association between preoperative serum cholesterol and prostate cancer recurrence: results from the SEARCH database. Cancer Epidemiol Biomarkers Prev. 2016;25(3):547–554. doi:10.1158/1055-9965.EPI-15-087626809276

 PubMed Web of Science ®Google Scholar

Allott EH, Farnan L, Steck SE, et al. Statin use, high cholesterol and prostate cancer progression; results from HCaP-NC. Prostate. 2018;78(11):857–864. doi:10.1002/pros.2364429717502

 PubMed Web of Science ®Google Scholar

Bhindi B, Xie WY, Kulkarni GS, et al. Influence of metabolic syndrome on prostate cancer stage, grade, and overall recurrence risk in men undergoing radical prostatectomy. Urology. 2016;93:77–85. doi:10.1016/j.urology.2016.01.04127015944

 PubMed Web of Science ®Google Scholar

Kang M, Jeong CW, Ku JH, Kwak C, Kim HH. Hypertriglyceridemia is a potential preoperative predictor for biochemical recurrence after radical prostatectomy. PLoS One. 2015;10(3):e0122438. doi:10.1371/journal.pone.012243825803284

 PubMed Web of Science ®Google Scholar

Komaru A, Kamiya N, Suzuki H, et al. Implications of body mass index in Japanese patients with prostate cancer who had undergone radical prostatectomy. Jpn J Clin Oncol. 2010;40(4):353–359. doi:10.1093/jjco/hyp16420064824

 PubMed Web of Science ®Google Scholar

Macleod LC, Chery LJ, Hu EY, et al. Metabolic syndrome, dyslipidemia and prostate cancer recurrence after primary surgery or radiation in a veterans cohort. Prostate Cancer Prostatic Dis. 2015;18(2):190–195. doi:10.1038/pcan.2015.1225823651

 PubMed Web of Science ®Google Scholar

Ohno Y, Ohori M, Nakashima J, et al. Association between preoperative serum total cholesterol level and biochemical recurrence in prostate cancer patients who underwent radical prostatectomy. Mol Clin Oncol. 2016;4(6):1073–1077. doi:10.3892/mco.2016.83127284447

 PubMedGoogle Scholar

Post JM, Beebe-Dimmer JL, Morgenstern H, et al. The metabolic syndrome and biochemical recurrence following radical prostatectomy. Prostate Cancer. 2011;2011:245642. doi:10.1155/2011/24564222096652

 PubMedGoogle Scholar

Rantaniemi L, Tammela TLJ, Kujala P, Murtola TJ. Blood cholesterol, tumor clinical characteristics and risk of prostate cancer progression after radical prostatectomy. Scand J Urol. 2018;52(4):269–276. doi:10.1080/21681805.2018.149296730362865

 PubMed Web of Science ®Google Scholar

Sanchis-Bonet A, Ortiz-Vico F, Morales-Palacios N, Sanchez-Chapado M. The association between metabolic syndrome and prostate cancer: effect on its aggressiveness and progression. Actas Urol Esp. 2015;39(3):154–160. doi:10.1016/j.acuro.2014.09.00925454266

 PubMed Web of Science ®Google Scholar

Shiota M, Yokomizo A, Takeuchi A, et al. The feature of metabolic syndrome is a risk factor for biochemical recurrence after radical prostatectomy. J Surg Oncol. 2014;110(4):476–481. doi:10.1002/jso.2367724898352

 PubMed Web of Science ®Google Scholar

Wettstein MS, Saba K, Umbehr MH, et al. Prognostic role of preoperative serum lipid levels in patients undergoing radical prostatectomy for clinically localized prostate cancer. Prostate. 2017;77(5):549–556. doi:10.1002/pros.2329628093792

 PubMed Web of Science ®Google Scholar