Therapeutic effect of transurethral needle ablation in non-bacterial prostatitis: Chronic pelvic pain syndrome type IIIa

Authors


Po Hui Chiang md phd, 106 Chong Cheng 3rd Road, Kaohsiung 800, Taiwan. E-mail: cphtem@yahoo.com.tw

Abstract

Aim:  Non-bacterial prostatitis is difficult to manage with conventional treatment. This study was undertaken to evaluate the therapeutic effect of transurethral needle ablation (TUNA) on men with chronic inflammatory non-bacterial prostatitis.

Methods:  Thirty-two patients with non-bacterial prostatitis (type IIIa) were treated with TUNA. The TUNA procedure, which uses radiofrequency energy, heats the prostate tissue to approximately 90–110°C over a 5-min period. Evaluation consisted of a prostatitis symptom severity score chart, the monitoring of the leukocyte count in the expressed prostatic secretion (EPS) and a subjective global assessment.

Results:  The decrease in the prostate symptom severity score chart at 3 and 6 months compared with the baseline assessment was statistically significant. Analysis of the leukocyte levels in the EPS in 14 patients was available. All 14 patients had a decrease in the EPS leukocyte count 3 months after treatment. However, six of these men (43%) still had EPS leukocyte levels above the normal indices (>10 white blood cells per high-power field). A second session of TUNA on these partial responders resulted in three of the six men obtaining a normal EPS leukocyte count. At 6 months following treatment, complete, partial and poor improvement in terms of subjective global assessment were noted in 60, 35 and 5% of patients, respectively. No major complications, including those of sexual dysfunction or retrograde ejaculation, were noted in this cohort.

Conclusions:  Transurethral needle ablation appears to be an easy, safe and effective treatment for men with chronic inflammatory non-bacterial prostatitis.

Introduction

Non-bacterial prostatitis, more recently classified by the American National Institute of Health (NIH) as chronic pelvic pain syndrome type III, is the most common form of prostatitis and also the most poorly understood in terms of etiology. There are both inflammatory (categorized by the NIH as type IIIa) and non-inflammatory (or type IIIb) chronic pelvic pain syndromes. The type IIIb non-inflammatory category was previously termed prostatodynia, which distinguished it from the type IIIa inflammatory category that was more often described by the use of the term non-bacterial prostatitis. The differential diagnosis between the two chronic pelvic pain types is based on the presence or absence of abnormally high levels of leukocytes in the prostatic fluid, indicating an inflammatory or a non-inflammatory response, respectively, within the prostate tissue, in the general absence of any identifiable bacteria. There are many contradictory studies focused on the role of fastidious organisms in the etiology of this disease. Persson & Ronquist found that the back-flow of urine could lead to high concentrations of urinary urate and creatinine in prostatic fluid, inducing a ‘chemical’ prostatitis.1 Urodynamic evaluations have also found an increased maximal urethral closure pressure and a diminished urinary flow rate in patients with chronic pelvic pain syndrome.2 Some researchers believe it is an autoimmune response of the prostate tissue.3

Whatever the cause, those suffering chronic pelvic pain symptoms do not usually respond to antibiotic therapy, or at best only enjoy symptomatic relief while taking this medication. Typically, the symptoms return shortly after ceasing the medication. The use of α-blockers, various anti-inflammatory agents, anxiolytics, herbal medications, as well as hot sitz baths and psychological support have been reported as producing limited effects but are rarely beneficial in the majority of patients over any significant length of time. There are also many reports that detail the heating of the prostate to approximately 43°C by transrectal microwave4 or transurethral balloon laser5 that have claimed to be beneficial in patients with non-bacterial prostatitis. Studies of thermotherapy by heating the prostate to 45–60°C by transurethral microwave thermotherapy (TUMT) have also shown relief of symptoms in 70% of men with non-bacterial prostatitis.6 However, leukocytosis of the expressed prostatic secretion (EPS) has been noted to persist following this form of treatment.

Transurethral needle ablation (TUNA; VidaMed, Fremont, CA, USA) was originally developed to treat benign prostatic hyperplasia (BPH) as a minimally invasive outpatient or office-based treatment option. Numerous studies have reported the safety and effectiveness of this procedure for BPH.7–9

In 1997, we reported the results of a pilot study that we conducted to examine the application of this treatment as a second-line treatment in selected patients with recurring symptoms of non-bacterial prostatitis that had failed to respond to medical therapy.10 The current phase II prospective trial was undertaken to determine the potential safety and efficacy of TUNA in the treatment of non-bacterial prostatitis.

Patients and methods

Thirty-two patients aged 35.3 ± 7.5 years (range 28–52 years) were selected with a clinical diagnosis of non-bacterial prostatitis persisting for a period of at least 6 months (defined as having symptoms of discomfort or pain in the pelvic region for at least the previous half year). All patients had >10 white blood cells (WBC) per high-power field (HPF) and negative cultures of expressed prostatic fluid or postprostatic massage urine (voided bladder 3). All patients had not responded to at least 4 weeks of antibiotic therapy (doxycycline, trimethoprim-sulfamethoxazole, norfloxacin, ofloxacin, or ciprofloxacin), prior to enrolment. Additionally, they had not responded to intraprostatic injection with amikacin or gentamycin. Tuberculosis prostatitis was ruled out by the polymerase chain reaction, acid-fast bacilli smear and culture for mycobacterium tuberculosis if there was a persistently large amount of inflammatory cells in the prostatic fluid expressates. The pretreatment urological evaluation was used to rule out any significant coexisting diseases. Patients with diseases that might have confused the diagnosis were excluded. Prostatitis symptom severity score questionnaires (Appendix I) were performed before treatment and again at 3 and 6 months after treatment.

All patients gave informed consent and were treated in an outpatient clinic setting. Patients were treated in the lithotomy position under topical anesthesia with intraurethral xylocaine 1% and intravenous sedation if necessary. The depth to which the radiofrequency (RF) needle antennae were to be deployed was obtained by measuring the transverse prostate diameter with transrectal ultrasonography (TRUS), dividing this measurement in half, and then subtracting 6 mm, so as to ensure that the needles remained within the prostatic capsule. Using TRUS, the volume of each prostate was estimated to be less than 25 cm3. Two planes consisting of four ablation sites in each lobe were created between the bladder neck and the verumontanum. One plane was located 0.5–10.0 mm distal to the bladder neck and the second plane was located 0.5–10.0 mm proximal from the verumontanum. The TUNA catheter (version III VidaMed) was positioned under direct vision using the dedicated, integral optics. The needle and sheath were advanced to the predetermined depth, and the sheath was retracted on each needle to provide 6-mm-deep shielding for the urethra. Power settings were determined by a nomogram within the TUNA RF generator (model 7200) and were automatically adjusted by monitoring the increase in temperature at the tips of the sheaths. During each ablation a constant and steady rise in temperature was achieved by increasing the power automatically over a 4-min period until temperatures of 50–60°C at the proximal edge of the lesion had been reached. This corresponded to a central lesion temperature of 90–100°C. Temperatures >50°C at the proximal edge of the lesion were maintained for 1–2 min. The urethral temperatures were carefully maintained below 43°C by gentle irrigation through an irrigation port on the catheter. EPS was obtained at 12 weeks and again at 24 weeks in 14 of the 32 patients after the procedure. The mean follow-up period was 14.2 ± 4.3 months (range 3–24 months, median 11.3 months). The unpaired Student's t-test and Wilcoxon rank sum test were used for parametric and non-parametric data analysis, respectively.

Results

Thirty-two patients completed the 3-month assessment. Twelve patients were lost to follow up at the 6-month assessment. The mean (± SD) symptom scores at baseline, 3 and 6 months were 15.4 ± 1.3, 6.4 ± 0.2 and 4.8 ± 0.6, respectively (Fig. 1). A significant improvement of both objective and subjective measurements occurred at 3 and 6 months after treatment (P < 0.05, t-test).

Figure 1.

Symptom score before treatment and at 3 and 6 months after treatment. Comparison with baseline (P < 0.05, t-test).

Given that it is more difficult to obtain EPS after treatment, only 14 of 32 patients were available in the follow up of the changes in the EPS. Nevertheless, all of these patients had a decrease in the leukocyte count of the EPS at 3 months after treatment. Six of these 14 men (43%) still had a leukocyte count >10 WBC per HPF at 3 months, despite a reduction compared with their pretreatment measurements. However, complete resolution (WBC count in EPS <10 per HPF) was noted in three of these six partial responders after a second TUNA treatment undertaken 3 months after the initial treatment. This improvement in 11 of the 14 patients (79%) available for this objective measurement was maintained during subsequent follow up. Three partial responders (21%) had abnormal WBC counts in their EPS at the 6-month follow up. The mean (± SD) WBC count in EPS per HPF at baseline, at 3 and 6 months were 113.7 ± 50.3, 23.9 ± 13.2 and 14.8 ± 9.6, respectively (Fig. 2).

Figure 2.

White blood cells (WBC) in expressed prostatic secretion of 14 patients available for evaluation before treatment and at 3 and 6 months after treatment. Comparison with baseline (P < 0.05, Wilcoxon rank sum test). HPF, high-power field.

All 32 patients were available for subjective assessment at the 3-month follow up, with 18 of the 32 (56%) reporting >75% improvement of all symptoms and 13 patients (41%) reporting >25% improvement. Only one patient (3%) reported a poor subjective assessment (<25% response compared to baseline). Of 20 patients available for subjective assessment at 6 months, 12 patients (60%) reported >75% improvement of all symptoms in the subjective global assessment, whereas seven patients (35%) reported >25% improvement at 6 months.

All patients suffered from micturition pain, perineal discomfort and mild hematuria for the first 2 days following treatment. This may have been a result of additional congestion within the prostate gland from edema caused by the heating of the tissue. Acute urinary retention occurred in two patients that subsided within 2 days. Hematospermia lasting for more than 1 month was observed in five patients. This was resolved in all five patients within 2 months. No abnormal changes in the routine blood and biochemical results (renal function, liver function, blood sugar and electrolytes) were seen following treatment. Semen analysis was studied on eight patients and this showed no deterioration of quality 3 months after treatment (Table 1). Indeed, there was a statistically significant trend in the improvement of semen motility post-treatment, compared to baseline measures.

Table 1.  Characteristics of semen analysis in eight patients
 Count
(×106/mL)*
Motility
(%)**
Normal
morphology
(%)***
  1. Wilcoxon rank sum test: *P > 0.05; **0.05 < P < 0.10; ***P > 0.05.

Pretreatment
(mean ± SD)
28.5 ± 18.730.5 ± 16.773.0 ± 22.3
After 3 months
(mean ± SD)
34.6 ± 12.249.4 ± 18.580.4 ± 31.6

Discussion

The TUNA device has previously been reported to treat BPH as a minimally invasive therapy performed as an outpatient or office-based treatment.8 Worldwide experience to date shows that the technique is an easy and safe treatment for BPH, producing significant improvement in both subjective symptom and objective measurements.7–9,11 It rarely results in sexual dysfunction or retrograde ejaculation that may be considered the most serious complications in young patients.

In 1997, we published the results of our pilot study on nine patients with non-bacterial prostatitis.10 The preliminary data proved promising without any serious complications and this prompted us to continue to enrol more patients to further evaluate the therapeutic effect of TUNA in the treatment of non-bacterial prostatitis.

The etiology of non-bacterial prostatitis remains an enigma. Some researchers have found increased intraprostatic pressure in patients with non-bacterial prostatitis.12 This may be caused by partial urethral obstruction, which has been demonstrated in a rat model.13The relationship between non-bacterial prostatitis and hyperthermia is not clear. Perachino et al. proposed that transurethral thermotherapy induces a long-term alpha blockade.14 Coagulative necrosis with cell death commences at temperatures of >45°C, with rapid thermoablation occurring at >60°C.8 In the present study, a urethral temperature of 43°C was maintained. When TUMT thermotherapy was used,4 interstitial temperatures of 45–60°C were achieved.6 Although more than half of the patients treated by microwave reported subjective improvements, the persistence of leukocytosis may be indicative of continued prostatic inflammation.6 The TUNA technique uses low-level RF energy to heat tissue within the prostate to 90–100°C. This effect may result in an intraprostatic sympathectomy that alters the afferent neurotransmissions that convey pain from the inflamed prostate gland. Another possibility is that the coagulative areas of necrosis caused by the TUNA procedure are converted to scar tissue, thereby accelerating the natural resolution of the inflammatory process and changing the mucosal permeability across the ductal and acinar epithelium of the prostate. The ability of TUNA to create areas of scar tissue selectively in the prostate may contribute to the objective decrease in leukocytosis that is not seen in patients treated by the lower temperature microwave thermotherapy.

The issue of sexual dysfunction and infertility after the treatment has been a matter of concern, as patients with non-bacterial prostatitis are generally younger than those with BPH. No patient suffered sexual dysfunction, retrograde ejaculation or deterioration of semen quality after TUNA in the present series. However, as other published series have reported an occasional incidence of retrograde ejaculation, the operator may have to be careful not to treat too near the bladder neck.

As the size of the prostate was typically less than 25 cm3, we found that two planes with a total of four ablation sites in each lateral lobe were usually sufficient to treat these small glands. The impedance monitoring by the RF generator prevented power being applied in areas of high impedance, such as in the fibrous prostatic capsule. The 90° positioning of the needles from the catheter shaft allowed easy access to the peripheral zone while protecting the neurovascular bundles outside the prostatic capsule from injury.

Chronic non-bacterial prostatitis is poorly understood, poorly defined, poorly treated and bothersome. Research and clinical efforts to help men with this syndrome have been hampered by the absence of a widely accepted, reliable and valid instrument to measure symptoms and quality-of-life impact.15 We modified the prostatitis symptom severity score chart from the Australian Prostatitis Protocol provided by VidaMed. This score chart can provide a valid outcome measure for men with chronic prostatitis. However, the placebo effect could not be ruled out with the use of the symptom score and subjective global assessment. Therefore, we also assess the change in the leukocyte count of the EPS. The leukocyte count of the EPS after the TUNA treatment was reduced in all patients 3 months after treatment although six (43%) still had abnormal elevation of WBC count in the EPS (>10 WBC per HPF). Repeating the TUNA treatment completely resolved the leukocytosis in three of these six patients. We are unsure if sealing the ducts by coagulative necrosis results in the reduced leukocyte count. It is possible that the reduction in the leukocyte count in the EPS represents a reduction of the inflammation within the prostate. There is some correlation between symptom score resolution and decrease in leukocyte count.

Chronic pelvic pain syndrome is the new term to describe non-bacterial prostatitis. The new consensus classification considers symptomatic patients without bacteria but who have inflammation in EPS, or post-massage urine or semen to have the inflammatory type of chronic pelvic pain syndrome (type IIIa).16 Those men who do not have elevated WBC counts in EPS, urine or semen are subclassified as non-inflammatory (type IIIb). This general consensus widens the non-bacterial prostatitis concept to include almost twice as many patients as the traditional category of non-bacterial prostatitis.17 There have been two papers published using TUNA for treatment of chronic pelvic pain syndrome (types IIIa and b).18,19 Leskinen et al. claimed that the efficacy of TUNA in chronic pelvic pain syndrome is similar to the efficacy of sham treatment.18 Aaltomaa & Ala-Opas reported that TUNA relieved symptoms in chronic pelvic pain syndrome patients and the need for medication was reduced.19 However, the differences between the TUNA and sham groups were not statistically significant. These data seem inconsistent with those of the present study. The outcome measures, study design, power settings and target temperatures are not consistent and this makes it more difficult to compare the treatments and evaluate their success. Universally, these studies were carried out on patients variously described as having chronic pelvic pain syndrome (types IIIa and b). Some patients with prostate-like symptoms but no evidence of inflammation within the prostate (type IIIb) may have disorders that have nothing to do with the prostate. In the present study, we do not conclude which classification is more suitable for the TUNA treatment. However, if the disorder is outside the prostate, possibly arising from a pelvic nerve dysfunction, as may be the case with prostatodynia (type IIIb), we do not think that TUNA will be effective. We therefore emphasize that confirmation of an abnormally elevated leukocyte count in the EPS, in the absence of any other urinary infection, is an essential indicator for using TUNA treatment. To our knowledge, one paper following our protocol reported the same promising results.20

We conclude that TUNA is a minimally invasive, easy and safe procedure that provides satisfactory results to most patients with the inflammatory subtype (IIIa) of non-bacterial prostatitis. However, this is a small, uncontrolled study that suffers from the lack of a control or a placebo group. A multicenter, randomized, placebo-controlled study is necessary to confirm that TUNA may be a promising new therapy for treating non-bacterial prostatitis.

Acknowledgments

We thank Mr Peter Robertson for his assistance in preparing this paper.

Appendix

Appendix I

Prostatitis symptom severity score chart

 Not at allMildModerateSevereIntolerable
 1. Penoscrotal pain (pain within your penis
and/or within your scrotum)
01234
 2. Perineal pain (pain between your anus and
scrotum)
01234
 3. Suprapubic pain (pain around the bone that
is in front of your bladder)
01234
 4. Painful ejaculation (pain when you have an
orgasm or following ejaculation)
01234
 5. Painful rectal examination (pain while the
urologist is feeling your prostate)
01234
 6. Low back/upper leg/groin pain (pain in any
or all of these areas)
01234
 7. Stranguria (intensely painful urge to pass
urine but difficulty in doing so)
01234
 Not at allLess than half
the time
About half
the time
More than half
the time
Almost
always
 8. Frequency01234
 9. Urgency01234
10. Dysuria01234
Total/40

Ancillary