Lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) develop through benign prostatic enlargement and bladder outlet obstruction [1]. Prostate enlargement does not occur homogeneously, however. Prostatic protrusion into the bladder often occurs and is a result of morphological changes [2]. Chia et al. [3] suggested that intravesical prostatic protrusion (IPP) is caused by the enlarging lateral lobes and the median lobe, and that the protrusion of the enlarged lobes causes a "ball-valve" type of obstruction, thus disrupting the funneling effect of the bladder neck and causing dyskinetic movement of the bladder during voiding. Thus, it is suggested that a prostatic mass with greater protrusion causes more severe voiding dysfunction by causing more serious bladder outlet obstruction [4-6]. It was also recently reported that increased IPP can affect the storage symptoms caused by stimulation of the bladder [7,8].

According to previous studies, IPP is significantly correlated with increased prostate volume, increased transitional zone volume, greater obstructive symptoms, decreased maximum flow rate (Qmax), and increased postvoid residual (PVR), which suggests that IPP may have clinical usefulness in predicting the need for treatment [9].

It was also recently reported that tamsulosin may be more effective in improving symptom scores and Qmax in patients with mild IPP than in those with moderate or severe IPP. It was suggested that the larger the IPP, the worse the voiding symptoms and the less the response to treatment with alpha blockers [10]. If so, other treatment methods should be applied as soon as possible. However, in the study mentioned above, the measurement of IPP was performed retrospectively and the study population was small. Also, the study included patients with moderate and severe IPP and large prostate sizes. As a result, the effects of treatment with an alpha blocker were somewhat reduced. For these reasons, well-designed studies are needed to assess the effect of IPP on treatment.

In the present study, therefore, we assessed the effect of IPP on the treatment effect of alpha-1 receptor antagonists in patients with BPH of 40 g or less. We divided the patients into two groups depending on the presence or absence of IPP at baseline and compared urinary symptoms, Qmax, and residual urine volume between the groups. The clinical significance of IPP was evaluated after the patients had been taking alfuzosin for 8 weeks.

This study was performed under Institutional Review Board approval. A total of 77 LUTS/BPH patients over 50 years of age treated with alfuzosin were enrolled prospectively. The study included only patients with BPH of 40 g or less. The patients were classified into two groups depending on the presence of IPP at baseline: the IPP group (41 patients) and the non-IPP group (36 patients). After the completion of urinalysis and routine laboratory tests at the first visit, prostate volume, prostate-specific antigen (PSA), International Prostate Symptom Score and quality of life (IPSS/QoL), Qmax, and PVR volume were compared between the groups. The clinical significance of IPP was evaluated by comparing the IPSS/QoL, Qmax, and PVR after the patients had been taking alfuzosin (10 mg, daily) for 8 weeks.

Qmax was measured by uroflowmetry (Duet Logic G2, Mediwatch Plc, West Palm Beach, FL, USA), prostate volume and IPP were measured by transrectal ultrasonography (6.5 MHz; SA-8000, Medison, Seoul, Korea), and PVR was evaluated by bladder scan (Cubescan Biocon-500, Mcube Technology, Seoul, Korea). If the PSA of the patients was elevated above 4 ng/mL, transrectal ultrasound-guided biopsies were performed to rule out prostate cancer, and only patients not diagnosed with prostate cancer were enrolled. Inclusion criteria were as follows: LUTS/BPH (less than 40 g) diagnosed by ultrasound, persistent LUTS/BPH for more than 6 months, IPSS≥12, IPSS storage subscore≥4 and voiding subscore≥5, outpatient, and aged 50 years and older. A Qmax of less than 15 mL/sec was an inclusion criterion. Patients with a medical history of urethral stricture, PVR≥200 mL, urinary tract infection, urinary tract stone disease, pelvic surgery, prostatic cancer, or neurogenic bladder or those taking anticholinergic agents were excluded at the start of evaluation. IPP was evaluated as measured by Nose et al. [11]. Length of IPP was obtained by measuring the vertical distance from the tip of the protrusion to the circumference of the bladder at the base of the enlarged prostate by transrectal ultrasound instead of the transabdominal approach of Nose et al. [11]. IPSS/QoL scores were obtained for all patients, and IPSS scores were subdivided according to storage symptoms subscore and voiding symptoms subscore.

The primary endpoint was whether alfuzosin improved symptoms in the IPP group compared with the non-IPP group after medication for 8 weeks. The secondary endpoints were whether alfuzosin improved QoL, Qmax, and PVR in the IPP group compared with the non-IPP group after medication for 8 weeks.

All values are presented as the mean±standard deviation. The significance of differences among groups was determined by using Student's t-test with differences considered significant at P<0.05.

The mean ages of the IPP and non-IPP groups were 67.2±6.9 and 64.5±8.1 years, respectively (P=0.125). The prostatic volumes of the IPP and non-IPP groups were 33.3±6.2 mL and 31.2±6.1 mL, respectively (P=0.276), at baseline. The mean length of IPP in the IPP group was 6.1±2.2 mm. The total PSA level was higher in the IPP group than in the non-IPP group at baseline. PSA and IPSS (total and voiding symptoms subscore) also differed significantly between the groups at baseline (P<0.05). However, the storage symptoms subscore, QoL, PVR, and Qmax were not significantly different between the groups (Table 1).

Comparison of parameters before and after 8 weeks of medication showed that alfuzosin improved the total IPSS and all subscores (P<0.001), QoL (P<0.001), Qmax (P<0.001), and PVR (P=0.030) more effectively in the non-IPP group than in the IPP group. The improvements in the total IPSS score in the IPP and non-IPP groups were 28.7±11.9% and 50.6±20.3%, respectively (P<0.0001). In the non-IPP group, the total IPSS significantly improved after 8 weeks of medication. The patterns of change in QoL and in the storage and voiding symptoms subscores were similar.

Qmax by uroflowmetry improved more in the non-IPP group than in the IPP group after 8 weeks of medication (P<0.001). Changes in PVR showed a similar pattern (Table 2).

Theoretically, if voiding symptoms are the main symptoms in LUTS/BPH, an alpha-1 receptor antagonist is considered to be a treatment of first choice. Similarly, if storage symptoms are the main symptom, combined therapy with an alpha-1 receptor antagonist and an anticholinergic can be an appropriate choice. However, not all LUTS/BPH is managed satisfactorily. IPP may be one of the causes of such unsatisfactory management.

IPP is caused by enlargement of the lateral lobes and the median lobe; the protrusions of these enlarged lobes cause voiding symptoms [3]. Recently, there have been many reports about IPP. IPP is a useful predictor for evaluating the success of a voiding trial after acute urinary retention [12]. However, most such reports focused on the length of IPP and voiding symptoms. A few studies reported on the relation between IPP and storage symptoms [7,8] or between IPP and clinical effects after alpha blocker medication [10]. In the study mentioned above, however, the measurement of IPP was performed retrospectively, and the study population was small. As shown in previous reports, IPP is significantly correlated with increased prostate volume, transitional zone volume, greater obstructive symptoms, decreased Qmax, and increased PVR [9]. Therefore, with an increase in IPP, Qmax is decreased and PVR is increased. As a result, the IPP group showed less of a decrease in the QoL score after 8 weeks of medication than did the non-IPP group [7]. In addition, most previous studies included all sizes of BPH and thus large IPP. In the present study, we prospectively included only patients who prostate size was smaller than 40 g. Our aim was to compare the differences in LUTS and in the effectiveness of an alpha blocker in patients with LUTS/BPH of similar prostate size according to the presence or absence of IPP.

In this study, baseline age, prostate volume, QoL, PVR, and Qmax did not differ significantly between the groups. Total PSA and IPSS (total and voiding subscore), however, did differ significantly between the groups at baseline (P<0.05). Total PSA was higher in the IPP group than in the non-IPP group, but the total PSA values of both groups were in the normal range and thus the difference was probably not significant clinically. However, compared with the IPSS after treatment, the percentage improvement was higher in the non-IPP group than in the IPP group. In the non-IPP group, all parameters were significantly improved at the endpoint of the study compared with the IPP group. Unlike in previous studies, however, IPP was not significantly related to increased prostatic volume, decreased Qmax, or increased PVR. These results imply that the prostate volume in this study was relatively small compared with previous studies. However, as previous studies have reported, IPP was related to worsening of voiding symptoms. Also, medication with alfuzosin yielded a better response in the non-IPP patient group. Furthermore, objective measurements such as changes in Qmax and PVR improved more in the non-IPP group than in the IPP group. Qmax by uroflowmetry was significantly improved in the non-IPP group after 8 weeks of medication. This result suggests that prostatic volume in this study was relatively small compared with previous studies.

The results of the present study suggest that because IPP is not related to initial IPSS, Qmax, or PVR, other study such as pressure-flow study is still needed for evaluation of bladder outlet obstruction. However, the presence of IPP implies a reduced effect of alpha blockers in the treatment of LUTS/BPH.

Our study did have some limitations. Even though it was a prospective study, the study population was small, and the enrolled patients did not undergo pressure-flow study. Despite these problems, however, the results of the present study suggest that the presence of IPP may indicate the need for a change in a therapeutic plan with further medical or surgical treatment.

In conclusion, even though prostate size was similar in the groups with and without IPP, treatment with alfuzosin for LUTS/BPH was less effective in improving symptom scores, PVR, and Qmax in the presence of IPP.