The baseline characteristics of 1297 patients are shown in Table 1. The baseline PSA was 4.0 (± 4.1, SD) ng/mL, 713 (55.0%) were in the low PSA group (1.6 ± 0.8 ng/mL), and 584 (45.0%) patients were in the high PSA group (6.9 ± 4.7 ng/mL). The average age of the patients was 69.7 (± 6.8) years, the mean total IPSS score was 23.4 (± 11.6), mean TPV was 68.3 (± 33.6) mL, mean BOO index was 24.2 (± 2.9). 294 (22.7%) patients experienced more than 1 AUR episode, and 442 (34.1%) patients underwent more than one P-Bx. The characteristics of low and high PSA groups are also shown on Table 1. The BMI, post-voided residual, number of preoperative AURs, baseline PSA, TZV, the number of preoperative P-Bx, and BOO all were statistically significantly different between the low and high PSA groups (p < 0.05)
Table 1
Baseline Patient Characteristics
Parameters (unit)
|
Whole population (n = 1297)
|
Low PSA group
PSA < 3.0ng/mL
(n = 713)
|
High PSA group
PSA > = 3.0ng/mL
(n = 584)
|
p-value
|
Age (year)
|
69.7 (± 6.8)
|
69.5 (± 6.6)
|
69.8 (± 7.2)
|
0.554
|
Body mass Index (kg/m2)
|
24.2 (± 2.9)
|
24.5 (± 3.0)
|
24.0 (± 2.8)
|
0.002
|
Symptom duration (months)
|
42.5 (± 64.6)
|
43.9 (± 72.9)
|
40.7 (± 52.8)
|
0.373
|
Preoperative medications for LUTS
|
|
|
|
|
Alpha blockers, n (%)
|
924 (71.2)
|
373 (28.8)
|
923 (71.2)
|
1.00
|
5-alpha reductase inhibitors, n (%)
|
447 (34.5)
|
849 (65.5)
|
447 (34.5)
|
0.412
|
International prostate symptom score
|
23.4 (± 11.6)
|
23.2 (± 11.2)
|
23.6 (± 11.8)
|
0.889
|
Maximum flow rate (mL/sec)
|
9.3 (± 4.7)
|
9.6 (± 4.7)
|
9.2 (± 4.7)
|
0.440
|
Post-voided residual volume (mL)
|
77.3 (± 100.9)
|
67.2 (± 91.0)
|
90.2 (± 111.0)
|
< 0.001
|
Acute urinary retention (times), n (%)
|
|
|
|
< 0.001
|
0
|
1003 (77.3)
|
600 (84.2)
|
403 (69.0)
|
|
>=1
|
294 (22.7)
|
113 (15.8)
|
181 (31.0)
|
|
1
|
261 (20.1)
|
103 (14.4)
|
158 (27.1)
|
|
2
|
21 (1.6)
|
6 (0.8)
|
15 (2.6)
|
|
3
|
9 (0.7)
|
2 (0.3)
|
7 (1.2)
|
|
4
|
3 (0.2)
|
2 (0.3)
|
1 (0.2)
|
|
Prostate specific antigen (ng/mL)
|
4.0 (± 4.1)
|
1.6 (± 0.8)
|
6.9 (± 4.7)
|
< 0.001
|
Prostate volume
|
|
|
|
|
Total prostate volume (mL)
|
68.3 (± 33.6)
|
54.3 (± 23.3)
|
85.4 (± 36.3)
|
< 0.001
|
Transitional zone volume (mL)
|
39.6 (± 26.6)
|
29.0 (± 18.8)
|
52.3 (± 28.8)
|
< 0.001
|
Prostate biopsies (times), n (%)
|
|
|
|
< 0.001
|
0
|
855 (65.9)
|
635 (89.1)
|
220 (37.7)
|
|
>=1
|
442 (34.1)
|
113 (15.8)
|
364 (62.3)
|
|
1
|
357 (27.5)
|
70 (9.8)
|
287 (49.1)
|
|
2
|
57 (4.4)
|
6 (0.8)
|
51 (8.7)
|
|
3
|
21 (1.6)
|
1 (0.1)
|
20 (3.4)
|
|
4
|
6 (0.5)
|
1 (0.1)
|
5 (0.9)
|
|
5
|
1 (0.1)
|
0 (0.0)
|
1 (0.2)
|
|
Bladder outlet obstruction index
|
24.2 (± 2.9)
|
39.0 (± 25.0)
|
51.1 (± 32.0)
|
< 0.001
|
Maximal detrusor pressure at Qmax
|
67.1 (± 27.5)
|
60.8 (± 25.2)
|
74.9 (± 28.1)
|
0.002
|
PSA, prostate specific antigen; LUTS, lower urinary tract symptoms; mean ± SD |
The perioperative parameters for all patients, and also according to low and high PSA groups are shown on Table 2. The mean values in the total patient group were; total operation time 59.8 (± 31.1), and enucleation weight 25.2 (± 27.1) grams. The mean hospital stay was 1.6 (± 1.4) days. The morcellation time, enucleation time, enucleation weight, total operation time showed statistically significant differences between PSA low and high groups (p < 0.05).
Table 2
Perioperative outcomes according to baseline PSA level
Parameters
|
Total population (n = 1297)
|
Low PSA group
PSA < 3.0ng/mL
(n = 713)
|
High PSA group
PSA > = 3.0ng/mL
(n = 584)
|
p-value
|
Total operation time (min)
|
59.8 (± 31.1)
|
49.9 (± 25.5)
|
71.7 (± 33.1)
|
< 0.001
|
Enucleation time (min)
|
38.1 (± 17.6)
|
32.9 (± 15.3)
|
44.4 (± 18.2)
|
< 0.001
|
Morcellation time (min)
|
10.0 (± 8.2)
|
7.6 (± 6.0)
|
12.6 (± 9.4)
|
< 0.001
|
Enucleation weight (gm)
|
25.2 (± 27.1)
|
16.1 (± 14.9)
|
36.3 (± 33.6)
|
< 0.001
|
Hospital stay (days)
|
1.6 (± 1.4)
|
1.5 (± 1.2)
|
1.6 (± 1.5)
|
0.213
|
Re-catheterization, n (%)
|
75 (7.2)
|
43 (7.5)
|
32 (6.7)
|
0.602
|
Clot evacuation, n (%)
|
45 (4.3)
|
22 (3.9)
|
23 (4.9)
|
0.438
|
Transfusion, n (%)
|
1 (0.1)
|
0 (0.0)
|
1 (0.2)
|
0.273
|
Bladder neck contracture, n (%)
|
2 (0.2)
|
1 (0.2)
|
1 (0.2)
|
0.902
|
Urethral Stricture, n (%)
|
2 (0.2)
|
5 (0.9)
|
2 (0.4)
|
0.464
|
Reoperation rate, n (%)
|
2 (0.2)
|
1 (0.2)
|
1 (0.2)
|
1.0
|
PSA, Prostate specific Antigen; mean ± SD |
The postoperative changes in PSA, IPSS, and Qmax were analyzed (Table 3). The IPSS and Qmax improved significantly for two weeks, 3 month, and 6 month postoperative follow-up. The PSA level was 4.0 (± 4.1) ng/mL at baseline and decreased to 1.0 (± 0.9) ng/mL at postoperative 6 months. This decrease was similar in the low PSA group, which decreased from baseline 1.6 (± 0.8) to 0.8 (± 0.5) ng/mL, and in the high PSA group which decreased from baseline 6.9 (± 4.7) to 1.2 (± 1.1) ng/mL at 6 months postoperatively. These changes were all statistically significant when the 6 months value was compared to baseline (p < 0.005).
Table 3
|
Baseline
|
Postop 2 weeks
|
Postop 3 months
|
Postop 6 months
|
p-value
|
IPSS (total)
|
23.4 (± 11.6)
|
15.0 (± 11.2)
|
11.4 (± 12.8)
|
10.1 (± 13.2)
|
< 0.001
|
Maximum flow rate (mL/sec)
|
9.3 (± 4.7)
|
20.0 (± 9.7)
|
21.5 (± 10.9)
|
22.0 (± 13.2)
|
< 0.001
|
Voided volume (mL)
|
175.4 (± 116.0)
|
193.0 (± 112.4)
|
208.0 (± 126.4)
|
220.1 (± 128.6)
|
< 0.001
|
PVR (mL)
|
77.3 (± 100.9)
|
26.3 (± 38.8)
|
18.8 (± 32.3)
|
18.1 (± 33.3)
|
< 0.001
|
PSA total (ng/mL)
|
4.0 (± 4.1)
|
-
|
-
|
1.0 (± 0.9)
|
< 0.001
|
Low PSA group
(Baseline PSA < 3.0ng/mL)
|
1.6 (± 0.8)
|
-
|
-
|
0.8 (± 0.5)
|
|
High PSA group
(Baseline PSA > = 3.0ng/mL)
|
6.9 (± 4.7)
|
-
|
-
|
1.2 (± 1.1)
|
|
Postop, Postoperative; PSA, Prostate Specific Antigen; IPSS, International Prostate Symptom Score; PVR, Post-voided residual volume; mean ± SD |
The natural history of PSA were analyzed. The PSA decrease from baseline to postoperative 6 months was shown in Fig. 1a. The decrease rate of PSA was 66.7 (± 23.6) % in the total PSA group, and 54.3 (± 23.9) % in the low group, and 79.6 (± 14.7) % in the high group. The PSA decrease rate showed statistically significant correlation with the resected volume (p < 0.001). The natural history of PSA were analyzed (Fig. 1b). Preoperatively, 713 (55.0%) patients were in the low PSA group, and 584 (45.0%) patients were in the high PSA group. Among the baseline low PSA group patients (n = 713), 709 (99.4%) decreased and maintained low postoperatively, and among the baseline high PSA group patients (n = 584), 556 (95.2%) were persistently postoperatively decreased.
In addition, the difference between high PSA and low PSA groups of preoperative PSA, relative to AUR, IPSS, TPV and BOOI, was analyzed using odds ratios. AUR was stratified according to groups with no AURs, and one or more episodes, IPSS stratified according to a cut-off level of 8 points [19], TPV stratified according to a cut-off level of 100mL [20], and BOOI stratified with a cut-off of 40 [21]. The high PSA group showed an increased risk of AUR ( > = 1 times) (odds ratio (OR) = 2.389, 95% confidence interval (CI) [1.828,3.122], p < 0.001), high TPV ( > = 100 mL) (OR = 8.368, 95% CI [5.560, 12.596], p < 0.001), and high BOOI ( > = 40) (OR = 2.389, 95% CI [1.828,3.122], p < 0.001). Multiple regression showed that AUR, number of P-Bx, TPV, and BOOI showed statistically significant positive correlations, while 5-ARI medication history, IPSS, and BMI showed negative correlations with preoperative PSA at 5% significance level (Table 4).
Table 4
Characteristics Associated with PSA using univariable and multivariable regression analysis
|
|
PSA
|
|
|
Parameters
|
Univariable analysis
|
|
Multivariable Analysis
|
|
Unadjusted OR (95% CI)
|
p-value
|
Adjusted OR (95% CI)
|
p-value
|
AUR
|
2.389 (1.828, 3.122)
|
< 0.001
|
1.928 (1.435, 2.596)
|
< 0.001
|
IPSS
|
0.727 (0.392, 1.346)
|
0.309
|
0.779 (0.394, 1.549)
|
0.471
|
TPV
|
8.368 (5.560, 12.596)
|
< 0.001
|
7.166 (4.734, 11.208)
|
< 0.001
|
BOOI
|
2.396 (1.912, 3.000)
|
< 0.001
|
2.030 (1.591, 2.593)
|
< 0.001
|
PSA, Prostate specific Antigen; CI, Confidence Interval; AUR, Acute Urinary Retention; IPSS, International Prostate Symptom Score; TPV, Total Prostate Volume; TZV, Transitional Zone Volume; BOOI, Bladder Outlet Obstruction Index |
The surgical pathology after HoLEP was described. Adenocarcinoma was detected incidentally in 83 (6.4%) of all patients, and 42 (5.9%) patients were in the baseline low PSA group, and 41 (70%) were in the baseline high PSA group (p = 0.426). The total Gleason score and tumor percentage were not statistically different between low and high PSA groups. Most of the patients had a tumor volume of 1% in both low and high PSA groups. 7 patients (0.5%) were also diagnosed with other cancers (bladder TCC (n = 4, 0.6%) prostate TCC (n = 3, 0.4%)), in addition to nodular hyperplasia and received follow-up treatment for cancer.
The characteristics of patients with elevated PSA 6 months postoperatively were evaluated. Among the 32 patients whose PSA was persistently elevated 6 months postoperatively, 4 (12.5%) patients were from the low PSA group, and 28 (87.5%) were from the high PSA group. In the patients whose PSA was persistently low at 6 months, 419 (33.1%) patients had underwent more than one P-Bx at baseline, whereas in the patients whose PSA was persistently elevated at 6 months, 23 (71.9%) patients had underwent more than one P-Bx at baseline.
The pathology of patients who underwent additional P-Bx after 6 month follow-up were also analyzed. Among the 4 patients who underwent postoperative P-Bx, one patient was diagnosed with prostatic adenocarcinoma.