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LUTS suggestive of BPH are a common condition in the present ageing male population . In the past 10–15 years, most men diagnosed with BPH were primarily treated medically, especially with α1-adrenergic blockers. These drugs have minimal side-effects, but are also less efficient than TURP . TURP has been the standard treatment for many decades and its complication rates are decreasing, but still it is associated with significant morbidity . Concurrently, several minimally invasive procedures have been developed with the intention of being as effective as TURP, but with less morbidity . However, most of these procedures are rarely used, which might partly be explained by a lack of durable long-term results.
A randomized controlled study comparing TURP, contact laser prostatectomy (CLP) and electrovaporization (EVAP) has been conducted at our medical centre in men with LUTS associated with BPH. Previously, we reported the subjective changes and urodynamic results at various intervals up to a mean follow-up of 4.3 years [5–7].
To analyse the durability of TURP, CLP and EVAP, we compared the extended long-term results of subjective changes, flowmetry, prostate volume, PSA level, morbidity, mortality and overall success rate of these minimally invasive procedures.
PATIENTS AND METHODS
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This prospective randomized controlled study was conducted between 1996 and 2001 in men aged >45 years with LUTS suggestive of BPH. All patients had a history taken, a DRE, urine analysis, blood analysis, free uroflowmetry, postvoid residual volume estimation, TRUS and urodynamic evaluation, including pressure-flow analysis. Inclusion criteria were a prostate volume of 20–65 mL and a Schäfer obstruction grade of ≥2. Exclusion criteria were those listed by the International Consensus Committee on BPH . TURP was performed with a standard 24 F resectoscope, CLP using a Nd:YAG laser and EVAP with a VaportrodeTM element (Gyrus-ACMI, Southborough, MA, USA). Details of the operative techniques and study design were described previously .
Subjective changes were measured using the IPSS , the associated quality-of-life question (QoL) , the Symptom Problem Index (SPI)  and the BPH Impact Index (BII) . These validated questionnaires were completed before and several times after surgery, including at 1 year afterward and after a mean follow-up of 4.3 years . Free uroflowmetry was performed at the same intervals, and the results only included if patients voided >150 mL. Serum PSA levels were measured before and at 1 year after surgery. Prostate volume was measured by TRUS before and at 6 months after surgery.
In 2008, we registered mortality, morbidity and re-operation rates of all prospectively randomized patients by chart review, history-taking and by approaching patients’ GPs. All men, who were alive and not previously excluded, were invited by letter and if necessary by telephone to visit the outpatient department. The same questionnaires and tests were used as during the previous studies. To obtain the maximum cooperation of patients, we chose to measure prostate volume by less-invasive transabdominal ultrasonography. In some patients it is difficult to measure prostate length by this method because the pubic bone causes a shadow. Therefore we determined prostate volume using the prolate spheroid formula, expressed as π/6 × (anteroposterior dimension) × (transverse dimension)2, shown to be an accurate method to estimate prostate volume by Terris and Stamey  and Bangma et al..
To increase the assessment of the durability of these surgical procedures, we studied the long-term success rates of these techniques. We used Kaplan-Meier life-table analysis to calculate the success rates and to adjust for incomplete follow-up. Success rate was defined as ‘1 – failure rate’. Failure was defined as: re-operation (for BPH or urethral stricture) and need for permanent or intermittent catheterization. An intent-to-treat analysis was used; men who crossed over to the TURP group, because of technical (equipment) failure, were regarded as a failure of the initial technique.
Long-term values for the available patients were compared to preoperative values for each treatment group; then differences between treatment groups were analysed. After examining whether a variable was distributed normally, results were tested for statistical significance by the Wilcoxon signed-rank test, Kruskal–Wallis test and by Mann–Whitney U-test. Statistical significance was indicated at P < 0.05.
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At baseline, 150 men with a mean (range) age of 66 (49–82) years were randomized to TURP (53), to CLP (49) or to EVAP (48). In 2008 we could account for 91% of these initial patients; only 13 were lost to follow-up. Thirty-nine patients (26%) had died, 11 (21%) in the TURP, 14 (29%) in the CLP and 14 (29%) in the EVAP groups; Table 1 lists why patients were not suitable for further evaluation.
Table 1. Reasons why patients were not suitable for further follow-up
|All patients at baseline||53||49||48|
|Surgery cancelled for medical problems||1||0||1|
|Technical (equipment) failure resulting in TURP*||0||5||5|
|Patient emigrated in first year||1||0||0|
|Died in first year||2||0||0|
|Morbidity within first year||2 (2)†||0||1 (1)†|
|Reoperation (TURP) within first year*||2 (1)†||1||2 (1)†|
|Operation of urethral strictures (first year)*||1 (1)†||2 (2)†||1|
|Suitable after 1-year follow-up||44||41||38|
|Reoperation (TURP) after first year*||1||2 (1)†||2 (1)†|
|Operation because of urethral stricture*||1||0||0|
|Chronic catheterization after retention*||1||2||2|
|(Cysto)prostatectomy for cancer||1||2||1|
|Died after first year||5||11||11|
|Not willing to cooperate||0||1||0|
|Lost to follow-up||6||2||5|
|Available for further evaluation in 2008||29||20||17|
The overall success rate is graphically represented in a Kaplan-Meier curve (Fig. 1). There was no statistically significant difference in overall success rate between the three groups (P= 0.24), despite equipment failures during the initial procedure not being disregarded. The failure rate (95% CI) at 10 years of follow-up was 0.11 (0.03–0.20) for TURP, 0.22 (0.10–0.35) for CLP and 0.23 (0.11–0.35) for EVAP. In the TURP group there were three re-operations for BPH, two re-operations for urethral strictures and one man who used chronic intermittent catheterization. In the CLP group there were five technical (equipment) failures resulting in crossover to TURP. Three patients were re-operated for BPH, two for re-operated for urethral strictures and two were chronically catheterized due to urinary retention. In the EVAP group, technical (equipment) failure during operation resulted in five patients crossing over to TURP. Four patients were re-operated for BPH, one was re-operated for urethral stricture and two patients were chronically catheterized for retention.
Figure 1. Kaplan Meier curve of overall success rate. Success rate = (1 – failure); failure was defined as; re-operation (for BPH or urethral stricture), technical (equipment) failure during surgery and necessity of permanent or intermittent catheterization. There were no statistically significant differences among the three treatments (P= 0.151).
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Eventually 66 patients (44% of the initial group; 84% of the eligible patients) could be analysed after a mean (sd, range) follow-up of 10.1(1.6, 6.9–12.7) years. Of these, 29 patients treated with TURP (55%), 20 with CLP (41%) and 17 with EVAP (35%) had a mean (sd) follow-up of 10.1 (1.6), 10.3 (1.8) and 10.0 (1.6) years, respectively. Their mean (sd) age was, respectively, 74.3 (7.6), 74.2 (9.3) and 72.5 (10.3) years. In these 66 men, Schäfer’s obstruction grades at inclusion for TURP, CLP and EVAP were 3.1 (0.9), 3.2 (1.3) and 2.9 (0.9), respectively. There were no statistically significant differences in duration of follow-up, age and obstruction grade among the three treatment groups.
Results of the questionnaires, flowmetry, PSA and prostate volume are listed in Table 2. Data at baseline, 1 and 4.3 years of follow-up are presented only of those patients who were available for the long-term follow-up in the present analysis. In all treatment groups, long-term values for subjective changes (IPSS, QoL, SPI, BII) were significantly better than preoperative values (P < 0.05). Between TURP, CLP and EVAP, there were no statistically significant differences in these objective values at any time during the follow-up. Fifty-four patients were assessed by uroflowmetry, of whom 39 were able to void >150 mL. The maximum urinary flow rate (Qmax) was still higher than the baseline value in all treatment groups, but it was only significantly higher (P= 0.008) in patients treated with TURP. Among the three procedures, there were no statistically significant differences in Qmax at any time point. There were no differences in PSA levels between TURP, CLP and EVAP, but only in patients treated with TURP were long-term PSA levels significantly lower (P= 0.009) than the preoperative values. Compared to baseline, prostate volume was statistically significantly increased (P= 0.021) in the EVAP group and unchanged in the CLP (P= 0.55) and the TURP groups (P= 0.32).
Table 2. Results of subjective changes, flowmetry, PSA level and prostate volume. Data are only presented for 66 patients who were available for follow-up measurements
|Medians (interquartile range) variable||Baseline||1 year||4.3 years||10.1 years*|
|IPSS|| || || || |
| TURP||13.5 (11.3–20.0)||2.5 (1.0–4.0)||2.0 (1.0–7.0)||6.0 (2.5–12.5)‡|
| CLP||20.0 (16.0–25.0)||3.5 (1.0–8.3)||7.0 (3.8–13.0)||8.5 (4.0–16.8)†|
| EVAP||20.0 (12.8–23.0)||2.5 (0.8–3.5)||7.5 (1.0–10.0)||13.0 (2.5–16.0)†|
|QoL|| || || || |
| TURP||4.0 (3.0–5.0)||0.0 (0.0–1.0)||1.0 (0.0–1.0)||1.0 (1.0–2.0)‡|
| CLP||4.0 (3.0–5.0)||1.0 (0.0–1.0)||1.5 (1.0–3.0)||1.0 (1.0–3.0)†|
| EVAP||5.0 (3.0–5.0)||1.0 (0.0–1.0)||1.0 (0.8–2.0)||2.0 (1.0–2.5)†|
|SPI|| || || || |
| TURP||10.5 (7.3–14.8)||0.0 (0.0–2.0)||1.0 (0.0–6.0)||2.0 (0.0–5.5)‡|
| CLP||15.0 (8.0–17.0)||0.0 (0.0–3.0)||2.0 (0.0–8.0)||6.0 (0.0–12.0)†|
| EVAP||13.0 (7.0–18.0)||0.0 (0.0–1.5)||1.0 (0.0–4.3)||3.0 (0.0–7.0)†|
|BII|| || || || |
| TURP||9.0 (5.3–12.8)||0.0 (0.0–3.5)||1.0 (0.0–3.0)||2.0 (1.0–4.5)‡|
| CLP||10.0 (6.0–12.0)||3.0 (1.0–4.0)||3.0 (1.0–7.3)||3.0 (1.0–8.8)†|
| EVAP||12.0 (6.0–13.0)||1.0 (0.0–2.5)||1.0 (0.8–4.3)||4.0 (1.0–6.0)†|
|Qmax, mL/s|| || || || |
| TURP||12 (8–14)||22 (16–30)||17 (16–21)||15 (10–20)†|
| CLP||10 (9–14)||28 (12–41)||18 (12–24)||14 (9–20)|
| EVAP||12 (7–15)||24 (21–26)||17 (6–21)||15 (10–20)|
|PSA level, ng/mL|| || || || |
| TURP||3.4 (1.5–5.8)||1.0 (0.5–1.9)||–||2.4 (0.6–3.9)†|
| CLP||2.9 (1.1–4.7)||0.8 (0.4–2.6)||–||3.0 (1.4–5.3)|
| EVAP||1.8 (1.2–4.2)||1.6 (0.8–2.4)||–||1.7 (0.8–2.8)|
|Prostate volume, mL|| ||(6 months)|| || |
| TURP||36 (29–45)||23 (15–31)||–||38 (32–52)|
| CLP||35 (29–43)||24 (18–27)||–||38 (29–46)|
| EVAP||28 (20–35)||20 (17–24)||–||43 (27–58)†|
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After a mean follow-up of 10.1 years, there were similar and durable subjective improvements for patients with LUTS suggestive of BPH after TURP, CLP and EVAP. Although similar between the three groups, only patients treated with TURP showed durable objective improvements in Qmax and PSA level.
The group size was calculated as described earlier . During this long-term follow-up, patients died or were lost to follow-up. The original study design was not powered for the eventual length of the follow-up and conclusions are therefore restricted. In all, 150 patients were included in the original study design; during the follow-up, we could account for 137. This means that only 9% of the patients were lost to follow-up; until recently, most of these patients lived in a nursing home, but exact information could not be retrieved. Due to various reasons, only 52% of the remaining patients were available for further analysis, i.e. 29 in the TURP group, compared to 20 in the CLP and 17 in the EVAP groups. This disproportion is caused by several factors. Initially, slightly more patients were randomized to TURP (53, vs 49 and 48). The overall failure rate of TURP was 11%, vs 25% for CLP and EVAP. This insignificant difference was mostly due to intraoperative technical (equipment) failure of CLP and EVAP (Table 1). In patients treated with TURP, technical problems did not occur. Finally, patients treated with TURP had less morbidity (respectively one vs three and one conditions) and mortality (respectively 11 vs 14 and 14) than patients treated with CLP and EVAP.
Failure was defined as re-operation, catheterization and intraoperative technical problems resulting in crossover to TURP. However, failure could also be defined slightly differently in terms of symptomatic changes compared to baseline. In an additional analysis (not shown), we included ‘IPSS decrease of <4 points compared to baseline score’, as defined by the Medical Therapy of Prostatic Symptoms study , in the definition of failure. However, there was still no statistically significant difference between the three treatment groups. Only one patient in the CLP group and none in the other groups used an α-blocker.
At baseline and after 6 months of follow-up, prostate volume was measured by TRUS; to maximize compliance in these elderly men, we chose to measure prostate volume transabdominally, which is less invasive than TRUS. The mean age of the included patients in this study was 73.8 years. Due to morbidity, decreased mobility and several other reasons, it is difficult to obtain a large number of responders in such an elderly population. Nevertheless, we achieved an adjusted response rate of 84%. In this study, there was a clear tendency that subjective changes were deteriorating. However, all three procedure types still showed statistically significant durable improvement in subjective changes compared to the preoperative values. The re-operation rate in our study (7%) is comparable to average re-treatment rates for TURP (3–14.5%) after 5 years .
In 54 of the 66 evaluable patients we performed uroflowmetry; 12 were not able to visit the outpatient department, due to advanced age, morbidity or travel distance. Another 15 patients were not able to void >150 mL; the Qmax of these patients were not representative and were excluded. Of the remaining 39 patients, all three groups still showed an improvement in Qmax, but there was only a statistically significant improvement in patients treated with TURP. Uroflowmetry was only performed once in every patient, although Qmax can vary each time. We are aware that relatively few patients were assessed by uroflowmetry, but it was not reasonable that these elderly patients visited the outpatient department many times. The significant improvement in Qmax at 10 years in the TURP group of only 3 mL/s is of little clinical relevance. Because this significance can occur by chance, we considered statistical significance at P≤ 0.01 instead of ≤0.05 as a correction for multiple testing. Nevertheless, the improvement in Qmax at 10 years was still statistically significant for patients treated with TURP. Also the PSA results for TURP at 10 years were still significant at P≤ 0.01, but we accept there were no clinically relevant differences among the three groups.
A few other studies have analysed the longer-term results of CLP and EVAP up to a maximum of 5 years. Tuhkanen et al. studied 52 patients with small prostates (<40 mL) and urodynamically confirmed obstruction treated with CLP and TURP; 42 (81%), who were analysed at 4 years, showed no significant difference between the groups in the relief of symptoms or in the rate of re-operations (4%). However, 32% of patients treated with CLP were again obstructed compared to 10% of TURP patients. Keoghane et al. analysed the 5-year results in a prospective trial of 152 initially randomized patients treated with TURP or CLP; only 57 (38%) were available for further analysis. Re-operation rates were 18% after CLP and 14.5% after TURP. There was no significant difference between the groups in AUA-7 symptom scores and Qmax.
Hammadeh et al. compared TURP with EVAP in a prospective study for 5 years; 53 of the 104 patients were available for follow-up. The re-operation rate was 13% for both groups, but there was a significant and maintained improvement in mean IPSS, QoL and Qmax, with no statistical difference between the groups.
There were relatively few patients in the present and the above-cited studies, making the statistical power low. Similar to our study, but with a shorter follow-up, Tuhkanen et al. reported a slight advantage of TURP over CLP in objective outcome variables. However, we found no clinically relevant differences in long-term results among the three treatment groups. Keoghane et al. and Hammadeh et al. found no differences among TURP, CLP and EVAP.
Randomized controlled long-term evaluations are not available for several minimally invasive techniques, even though they were introduced long enough ago . Currently, photoselective vaporization of the prostate (PVP) using potassium-titanyl-phosphate laser is considered the most promising procedure. This new technique was first described in 2003, reporting good outcomes and minimal morbidity up to a mean follow-up of 3 years [19,20]. Holmium enucleation of the prostate (HoLEP) is also a widely used technique reporting good results with a follow-up to 6 years . More long-term evaluations of randomized controlled studies including PVP and HoLEP are eagerly awaited.