The first two papers in this section are on the topic of laser therapy for BPH. This is obviously a much-visited topic, but these papers help to throw further light on the subject. Is the laser the best way of treating this condition? We need more evidence to answer this question, and hopefully we will be able to give our patients the correct response when they ask us, based on papers such as these.
To evaluate the long-term effects, including durability, of interstitial laser coagulation (ILC) in patients with symptomatic benign prostatic hyperplasia.
PATIENTS AND METHODS
In all, 49 men (median age 68 years, range 52–80) were treated with ILC; 22 men were assessed for a median (range) of 54 (46–61) months. Information on the timing and type of re-treatment were collected for the remaining patients.
The median (quartiles) International Prostate Symptom Score decreased from 22 (19–28) at baseline to 13 (5–21), a decrease of 41%. The peak urinary flow increased by 20% to 10.2 (8.7–12.9) mL/s. Twenty-two patients were re-treated (by any type) after ILC, giving a re-treatment rate of 50%.
There were moderate effects on voiding variables and a high re-treatment rate during the long-term follow-up after ILC. It seems reasonable that the use of ILC is restricted to selected, high-risk patients.
interstitial laser coagulation
peak urinary flow rate
average urinary flow rate
postvoid residual volume.
The application of laser energy for treating LUTS suggestive of BOO caused by BPH (symptomatic BPH) has gained interest during the last 10–15 years. Various surgical techniques were introduced, with minimal peri-operative morbidity and promising short-term results . One of the many laser techniques is interstitial laser coagulation (ILC). We previously presented the 1-year results after ILC in a group of 49 patients. The IPSS decreased by about half from the baseline level and there was, at 1 year, a modest increase in peak urinary flow rate (Qmax). Patients with obstructed voiding on pressure-flow evaluation became partly unobstructed after ILC. Immediately after ILC about two-thirds of the patients had urinary retention for <1 week; a comparable proportion of patients reported perineal pain a few days after ILC .
Thus, the purpose of the present study was to assess the proportion of patients who required additional treatments after ILC, and to describe changes in symptoms and urinary flow during the long-term follow-up.
PATIENTS AND METHODS
Between June 1995 and December 1996, 49 patients with LUTS were treated with ILC in our outpatient clinic. The initial assessment included taking a history and a physical examination, urine analysis, urine culture, routine haematological and chemical blood examinations including PSA and creatinine levels, and cysto-urethroscopy. Informed consent was obtained after verbal and written information had been understood and accepted by each patient. The inclusion criteria were a clinical unequivocal benign prostate, with a history of >3 months in patients aged >45 years, an IPSS of >10 points and a Qmax of <15 mL/s. The exclusion criteria were recurrent UTI, urinary retention treated with clean intermittent catheterization or an indwelling catheter, prostate cancer, a serum PSA level of >20 ng/mL, serum creatinine level of >150 µmol/L, postvoid residual volume (PVR) of >300 mL, previous pharmacotherapy for LUTS (5α-reductase or α-receptor blockade) or a prostatic surgical procedure other than biopsy, pelvic radiotherapy, lower midline incision of the abdomen, neurological disorders that might involve bladder function, and infravesical obstruction from other causes than BPH.
The Qmax, voided volume and average urinary flow (Qave) were recorded using the Urodyn 1000 (Dantec, Skovlunde, Denmark) system. Voids with voided volumes of <120 mL, were not accepted, otherwise uroflowmetry was recorded in duplicate. The voiding with the highest Qmax was considered the most representative and was selected for further calculations. The PVR was calculated from suprapubic ultrasonography, using the three-coordinate technique . TRUS images of the prostate were obtained using a type 1846 real-time scanner (Brüel & Kjær, Denmark) with a 7-MHz multiplane transducer (type 8551). Prostate volume was calculated using the formula for an ellipsoidal mass. Before ILC the median (quartiles) prostate volume was 41.9 (27.7–54.2) mL. Random or targeted 18 G needle biopsies were taken in all patients with a serum PSA of >10 ng/mL or from focal areas, to exclude carcinoma of the prostate.
An 830 nm diode-laser device was used in all patients (Indigo, Palo Alto, CA, USA). Energy was delivered at an initial power setting of 10 W, with subsequent decrements at a pre-set time of 4 min per puncture. The diffuser tip was inserted using a cystoscope with a narrow working channel, to provide adequate support for the fibre inserted into the prostatic tissue, under direct visual guidance up to its marker. In general, the sites of fibre placement were chosen to coagulate the bulk of hyperplastic tissue. Thus, the total number of fibre placements varied depending on the size and configuration of the prostate. Individual fibre placements were spread by 0.5–1.0 cm and/or made at different angles, beginning at the apex at the level of the colliculus seminalis. To prevent thermal damage to the dorsal capsule and adjacent rectum, the lateral lobes were always punctured in the lateral or ventrolateral direction, never in the dorsal direction. If a median lobe was present, it was treated with one or more punctures in the direction of the bladder. Again, dorsal-directed punctures were avoided to prevent subtrigonal lesions. Irrigation was necessary only to provide optimal vision during punctures. The median (range) number of fibre punctures per prostate was 6 (4–8) and the energy delivered to each prostate was 8.67 (5.79–12.15) kJ. The ILC was conducted by one surgeon (L.D.), and was described previously .
Only data available until the date of re-treatment, or from patients with no additional treatment during the follow-up, were used for the analysis. For all 49 patients the follow-up was 48 (1–61) months. The different methods of re-treatment and their timing are shown in Table 1. For the 22 men who had no additional therapy for LUTS the long-term follow-up was 54 (46–61) months, and included the IPSS, urine analysis, serum creatinine and PSA levels, uroflowmetry and calculation of PVR, according to the criteria of the baseline evaluation.
|Reasons for exclusion||n|
|Treatment with α1-receptor antagonist||1|
|Treatment with α1-receptor antagonist||2|
|Bladder neck incision||1|
|Clean intermittent catheterization||1|
|Diagnosis of pancreatic tumour||1|
|Lost to follow-up||1|
|Treatment with α1-receptor antagonist||5|
|Treatment with 5α-reductase inhibitor||1|
|Treatment with muscarinic antagonist||2|
|Diagnosis of pulmonary cancer||1|
The median (quartile range) is given unless otherwise indicated. The Friedman two-way anova, followed by the Mann–Whitney U-test, was used to compare independent samples, and the Wilcoxon matched-pairs signed-ranks test was used to compare related samples, with P < 0.05 (two-tailed) considered to indicate statistical significance . Re-treatment rates were calculated and plotted using the Kaplan–Meier method .
Five of the 22 patients on ILC monotherapy were unavailable for physical examination but they all completed questionnaires on the effects of ILC, including the IPSS. The remaining 17 also had a thorough physical examination in the outpatient department. The patients available for long-term follow-up had a median age of 68 (56–78) years at inclusion, comparable with the group receiving additional treatment. These men had an IPSS of 13 (5–21), significantly (P < 0.001) lower than the baseline value of 22 (19–28), but higher (P < 0.01) than that at 3 months, Table 2. The relative decrease in IPSS from baseline was 41 (16–81)%. There were nine of 22 patients with a ≥ 50% and 13 with a ≥ 25% improvement in the IPSS at the long-term evaluation. The quality-of-life index score was 3 (1–4), significantly (P < 0.05) higher than that at 1 year. The Qmax increased by 20 (− 10, 83)% from baseline, to 10.2 (8.7–12.9) mL/s at the long-term follow-up (P < 0.05). The Qave increased from 4.3 (3.4–5.4) to 5.4 (3.7–6.6) mL/s (P < 0.05). Voiding volumes and PVR did not change significantly (Table 2).
|Number of patients||49||48||40||22|
|IPSS||22 (19–28)||8 (5–13)a||11 (7–18)ad||13 (5–21)ad|
|Quality-of-life index||5 (3–5)||2 (1–3)a||2 (1–3)a||3 (1–4)adf|
|Number of patients||49||47||40||16|
|Qmax, mL/s||8.6 (6.4–10.4)||11.1 (9.0–14.1)a||9.9 (7.9–13.1)bd||10.2 (8.7–12.9)c|
|% increase in Qmax||–||38 (16–76)a||13 (−4 to 63)bd||20 (−10 to 83)c|
|Qave||4.3 (3.4–5.4)||5.5 (4.3–7.6)a||4.7 (4.0–6.3)ce||5.4 (3.7–6.6)c|
|Voided volume, mL||189 (165–242)||221 (183–298)c||177 (144–258)e||213 (171–292)|
|PVR, mL||104 (57–164)||97 (46–154)||78 (43–160)||67 (33–103)|
During the complete follow-up after ILC, 22 of 44 patients (50%) had an additional treatment due to an unsatisfactory response to ILC alone. Eleven of these patients (25%) had pharmacotherapy, nine (21%) had TURP, one had a bladder neck incision and one started clean intermittent catheterization as a second-line therapy. Five patients were censored; two due to concomitant cancer (lung and pancreas) with deterioration of their health status; two who died from unrelated reasons; and one was lost to follow-up (Table 1).
The interval from ILC to starting the various second-line treatments are shown in the Kaplan–Meier plot (Fig. 1). The transfer of patients from the ILC-only group to other treatments seemed to be uniform throughout the various periods after ILC, with a tendency to a more pronounced change to other treatments at 1–2 years after ILC.
Prostate tissue was available for histological examination after TURP as second- or third-line therapy in 14 patients; histology confirmed BPH in 13, and adenocarcinoma in one (Gleason score 2 + 3 = 5, T2M0), and he had external beam radiotherapy, with a complete response.
The baseline values of IPSS, Qmax, PVR and prostate volume in the groups with and with no additional treatment were comparable. The serum creatinine level was 93 (87–110) µmol/L, compared to 105 (98–115) at baseline (P < 0.05). The serum PSA level was 4.2 (1.6–6.3) ng/mL, and comparable with the baseline value.
The vast majority of previous studies of ILC are based on 6- and 12-month data; the present long-term study shows that acceptable improvements in symptoms and uroflow were maintained in about half the patients at >4 years after ILC. The 20% increase in Qmax was modest and comparable with an increase of 23% reported by Terada et al. in a follow-up after ILC of ≥ 5 years. The present median IPSS was 13, comparable to that reported by Terada et al. By contrast, in the present study there were no significant changes in PVR after ILC. The present prostate volume of 41.9 mL before ILC was comparable with the corresponding volume of 45.8 mL reported by Terada et al., and of 39 mL reported by Floratos et al.. After a median follow-up of 34 months, Floratos et al. reported a decrease in IPSS, from 20 at baseline to 10, and an increase in Qmax from 8.0 to 12.0 mL/s. Muschter et al.[8,9] reported durable 3-year results, but neither of the two studies by Muschter et al. gave any information on the proportion of patients eventually assessed at 3 years, nor data on the selection of patients assessed at 3-years. This flaw makes the conclusions of these two studies of limited value.
ILC has been compared with TURP in a prospective and randomized study . After a follow-up of 2 years, the improvements in subjective and objective variables persisted in the group treated with ILC, but were worse than the improvements in the TURP group. Data from more extended follow-up are not available.
Durability is, in addition to effectiveness and operative morbidity, a key issue in the evaluation of laser treatment. In the present study, 22 of 44 patients (50%) required re-treatment during the follow-up, which compares to 15% at 1 year . Terada et al. reported a 5-year re-treatment (TURP or pharmacotherapy) rate of 43%, and Floratos et al. a re-treatment rate of 41% after 3 years. The present 50% re-treatment rate after 54 months is therefore comparable to those in previous studies. A second TURP was needed in 21% of patients in the present study. Terada et al. reported a 5-year TURP rate of 22% after primary ILC, which is thus comparable. The possibility of a second TURP after primary treatment using the TURP was assessed by Roos et al., who reported that the percentages of patients having a second TURP were 12.0%, 15.5% and 12.0% in Oxfordshire, Manitoba and Denmark, respectively, when patients were followed for up to 8 years after a primary TURP. In Austria, the actuarial cumulative incidence of a secondary TURP after primary TURP was 7.4% after 8 years, and the overall incidence of a secondary endourological procedure within 8 years was 14.7% after TURP . A large-scale study from Australia showed that the incidence rate of the first repeat TURP at 8 years was 6.6%. Stephenson et al. reported an 8-year incidence rate of a repeat TURP as 12.0–20.2%. From these data, the average annual incidence rate of a repeat TURP after primary TURP is 0.8–2.5%. The variability in data collected worldwide suggests that several factors are important for the long-term outcome, e.g. selection of patients for the procedure, age, choice of operative technique, availability of health care, etc. In the present study the mean annual secondary TURP rate after ILC was considerably (two to six times) higher than the international data for repeat TURP after a primary TURP.
TURP is associated with a small risk of death and several complications with a low incidence, e.g. bleeding, infection, urethral stricture, urinary incontinence and erectile dysfunction. More than half of the patients have retrograde ejaculation after TURP and a third have an unfavourable result at 3 months . ILC is a safe procedure ; immediately after ILC there was urinary retention and dysuria for a few days in most patients .
In the Indigo 830 nm diode laser device we used, energy was delivered with pre-set power decrements at a pre-set time per puncture. Later, a modified version of the energy-delivery protocol was introduced, including a temperature sensor at the tip of the fibre giving temperature feedback to the generator. Heating at the apex required less energy to achieve and maintained higher temperatures than at the base and median lobe of the prostate . Good clinical results were obtained at a follow-up at 2 years ; a more extended follow-up is highly desirable.
How does the re-treatment rate after ILC compare with drug therapy? In a recent report, the re-treatment rates up to 3 years for the different α-blockers tamsulosin, alfuzosin and terazosin were 27%, 37% and 49%, respectively . These rates of treatment failure compare fairly well with the values after ILC.
Results from different studies should be compared cautiously; the present study was small and included no comparison with other treatments, allowing only limited conclusions. The selection of patients might differ among studies; these differences will be reflected in treatment outcome.
The technical procedure followed during treatment was rather detailed, but the results reported here represent the initial experience of the surgeon. The association between surgeon’s experience with ILC and outcome of treatment is controversial. Terada et al. analysed independent predictive variables for success or failure with ILC, and found no significant effect of experience, but after stratification of patients in ‘early’ and ‘late’ ILC treatments, Ng et al. reported that treatments after the initial phase were associated with a higher Qmax at the follow-up, and with no increase in adverse events. Despite these limitations, an overall re-treatment rate of 50%, including a secondary TURP rate of 21% at >4 years of follow-up, are not encouraging for the future of this technique, particularly in the light of recent experiences with tissue-vaporization laser techniques .
In the present study, there was a significant decrease in serum creatinine levels during the follow-up; this effect should be considered a result of an improved bladder outlet, decreased pressure in the urinary tract and less strain on renal function.
In conclusion, there were moderate effects on subjective and objective voiding variables in a long-term follow-up after ILC, together with a high re-treatment rate. As the morbidity with ILC is modest, this method might be an option for the invasive treatment of selected patients with high-risk factors and in a poor medical condition.
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