Targeted transurethral microwave thermotherapy versus alpha-blockade in benign prostatic hyperplasia: outcomes at 18 months.

OBJECTIVES: To compare directly the efficacy, safety, and durability of targeted transurethral microwave thermotherapy with that of alpha-blocker treatment for lower urinary tract symptoms of benign prostatic hyperplasia. METHODS: In a randomized, controlled clinical trial, 52 patients with lower urinary tract symptoms due to benign prostatic hyperplasia received terazosin treatment and 51 underwent microwave treatment under topical anesthesia. The patient evaluation included the International Prostate Symptom Score, peak flow rate, and quality-of-life score before microwave treatment or initiation of terazosin treatment and at periodic intervals thereafter up to 18 months. RESULTS: The mean International Prostate Symptom Score, peak flow rate, and quality-of-life score all improved significantly in both groups by 6 months. However, the magnitude of improvement was significantly greater in the microwave group than in the terazosin group. The significant between-group differences observed at 6 months in the mean International Prostate Symptom Score, peak flow rate, and quality-of-life score were fully maintained at 18 months, at which time the improvements in these three outcome measures were significantly greater (P <0.0005), by 35%, 22%, and 43%, respectively, in the microwave group than in the terazosin group. The actuarial rate of treatment failure at 18 months was significantly greater by sevenfold in the terazosin group. Adverse events were generally infrequent and readily manageable in both groups. CONCLUSIONS: Although the initial onset of terazosin action was more rapid, the longer term clinical outcomes of targeted microwave treatment were markedly superior. The more favorable results in patients who underwent microwave treatment were maintained for at least 18 months.

Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men.

PURPOSE: We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml. who were diagnosed with benign prostatic hyperplasia after initial biopsy. MATERIALS AND METHODS: In this prospective study 1,051 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. RESULTS: Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1,051 subjects. Prostate cancer was detected on repeat biopsy in 10% of subjects (83 of 820) with negative initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) and eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78% and 52%, respectively. ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PSA density, 61.8% for PSA density and 60.3% for total PSA. CONCLUSIONS: At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.

Pretreatment prostate-specific antigen as an outcome predictor of targeted transurethral microwave thermotherapy.

OBJECTIVES: To evaluate pretreatment serum prostate-specific antigen (PSA) as an outcome predictor of targeted microwave thermotherapy. METHODS: Seventy-one patients with lower urinary tract symptoms of benign prostatic hyperplasia underwent targeted transurethral microwave thermotherapy using the Targis system. Outcomes 12 months after treatment were evaluated by the International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and quality-of-life (QOL) score. The ability of PSA to predict outcomes was evaluated by linear and logistic regression and receiver operating characteristic curve analysis. RESULTS: Higher pretreatment PSA levels were significantly predictive of an absolute IPSS change of -7.5 or less for patients with moderate baseline symptoms or - 15 or less for those with severe baseline symptoms; an absolute Qmax change of 5 mL/s or greater; an absolute QOL score change of -3 or less; an IPSS at 12 months of 7 or less; a Qmax at 12 months of greater than 12 mL/s; and a QOL score at 12 months of 1 or less. Nevertheless, even without taking pretreatment PSA into account, most patients benefitted substantially from targeted microwave thermotherapy. Thus, 74%, 71%, and 79% of all eligible patients improved 50% or more in IPSS, Qmax, and QOL score, respectively, at 12 months compared with baseline. No significant association between PSA and either prostate or transition zone volume could be demonstrated. CONCLUSIONS: Most patients benefit substantially from targeted microwave thermotherapy. However, higher PSA levels are significantly predictive of more favorable outcomes. This association may reflect patient-to-patient differences in the relative abundance of PSA-producing epithelial cells in the transition zone of the prostate.

Predictability and significance of multifocal prostate cancer in the radical prostatectomy specimen.

Multifocal prostate cancer has been reported in 50-76% of all cases of radical retropubic prostatectomy (RRP) specimens, but the clinical and prognostic significance of this finding is still unclear. A retrospective analysis of patients who underwent RRP between 1993 and 1997 was performed. Preoperative screening parameters and 4-mm RRP specimen sections were examined. The location, Gleason score, and extracapsular extension of the tumor recorded. Three hundred eight cases were reviewed. Mean follow-up was 4.2 +/- 1 years (range 2-6 years). Two hundred six patients (66.9%) had multifocal prostate cancer and 102 (33.1%) had unifocal prostate cancer. Of those with multifocal disease, 63% had two foci and 37% had three or more foci. There were statistical significant differences between both groups with respect to preoperative prostate-specific antigen (PSA) density of the transition zone (PSA-TZ), free/total (f/t) PSA, as well as percentage of patients with organ confined disease, high-grade tumors, and local recurrence. PSA-TZ (p = .001) and f/t PSA (p = .004) were significantly different between patients with unifocal and multifocal disease (0.9 vs. 2.2 ng/mL/cc and 18% vs. 6.5%, respectively). However, preoperative PSA (11.2 vs. 12.8 ng/mL; p = .09) and PSA density (0.17 vs. 0.19 ng/mL/cc; p = .07) were not able to predict unifocality or multifocality. These data suggest that multifocal prostate cancer is associated with higher grade, stage, and recurrence rate than unifocal prostate cancer. Preoperative PSA-TZ (> 1.5 ng/mL/cc) and f/t PSA (<9%) may predict multifocality in the RRP specimen.

Insulin-like growth factor 1 (IGF-1), IGF-1 density, and IGF-1/PSA ratio for prostate cancer detection.

OBJECTIVES: Recent studies suggest an association between increased serum levels of insulin-like growth factor 1 (IGF-1) and an increased risk of prostate cancer (PCa). We prospectively analyzed the value of IGF-1, IGF-density (IGFD), and IGF-1/prostate-specific antigen (PSA) ratio for early detection of prostate cancer. METHODS: IGF-1, IGFD, and IGF-1/PSA ratio were determined prospectively during an 11-month period in the serum from 245 consecutive white men with PSA levels between 2.5 and 15 ng/mL. Octant biopsy (including transition zone biopsy) was performed. A second biopsy was performed 6 weeks later if the first biopsy was negative. Prostate volume was measured using transrectal ultrasound and the prolate ellipsoid method. Receiver operating characteristic curves were performed to compare tests. RESULTS: No evidence of malignancy was found in 174 patients (71%), and PCa was found in 71 (29%). The mean age for patients with no evidence of malignancy and those with PCa was 67.7+/-9 and 65.7+/-6 years, respectively (P = 0.17). IGF-1, IGFD, IGF-1/PSA ratio, and PSA were significantly higher in patients with PCa than in those with benign disease (P = 0.03, P = 0.045, P = 0.001, and P = 0.018, respectively). The area under the curve value derived from the receiver operating characteristic curves for IGF-1/PSA ratio, PSA, IGFD, and IGF-1 was 71%, 61%, 60%, and 58%, respectively. At 95% sensitivity, the specificity of the IGF-1/PSA ratio was significantly greater than that of all other parameters (P<0.0001 ). An IGF-1/PSA cutoff value of 25 afforded a 95% sensitivity for detecting PCa and would have avoided unnecessary biopsies in 24.1% of patients. CONCLUSIONS: Although IGF-1 and IGFD were unable to enhance the performance of PSA in our study, the IGF-1/PSA ratio significantly improved PCa detection over the use of PSA alone. Thus, increased IGF-1 levels (i.e., the IGF-1/PSA ratio) may not only be associated with an increased PCa risk but may also be a useful tool for early detection.

High-energy transurethral microwave thermotherapy in patients with acute urinary retention due to benign prostatic hyperplasia.

OBJECTIVES: To evaluate the efficacy and safety of targeted high-energy transurethral microwave thermotherapy (HE-TUMT) in the treatment of acute urinary retention (AUR) due to benign prostatic hyperplasia (BPH). METHODS: In this prospective cohort study, 31 patients with painful AUR due to BPH underwent HE-TUMT. Patient evaluation before treatment and during a 12-week follow-up interval included determination of International Prostate Symptom Score (IPSS), quality of life (QOL) score, peak flow rate (Qmax) by uroflowmetry, and postvoid residual urine. Patients also underwent urodynamic evaluation before treatment and at 16 weeks. RESULTS: By 4 weeks after HE-TUMT, 29 (94%) of 31 patients had regained the ability to void spontaneously. The actuarial median time for restoration of spontaneous voiding was 3.0 weeks (95% confidence interval [CI] 2.2 to 3.8). At 12 weeks, the mean IPSS (9.4; 95% CI 8.3 to 10.5) was 50% below (P <0.0005) that before retention (18.9; 95% CI 18.2 to 19.6). Improvements in the mean QOL score were similar in pattern and relative magnitude to those in the mean IPSS. A 69% increase in mean Qmax (P <0.0005) determined by uroflowmetry was observed by 12 weeks versus 1 week after HE-TUMT. Complications were infrequent. CONCLUSIONS: This study provides preliminary evidence that HE-TUMT may potentially afford a novel and useful option for the patient with AUR who is not a suitable candidate for surgery.

Temporary intraurethral prostatic bridge-catheter compared with neoadjuvant and adjuvant alpha-blockade to improve early results of high-energy transurethral microwave thermotherapy.

OBJECTIVES: The maximal effect of transurethral microwave thermotherapy (TUMT) for lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) occurs 3 to 6 months after treatment. In the acute period after TUMT, little change in symptoms, quality of life (QOL), and peak urinary flow rate (Qmax) is observed versus baseline. Some men may also develop acute urinary retention secondary to thermally induced edema. Recent reports suggest that early results of TUMT may be improved with concomitant use of either a temporary intraurethral prostatic bridge-catheter (PBC) or neoadjuvant and adjuvant alpha-blocker therapy. This report compares the results of these two adjunctive modalities directly. METHODS: This nonrandomized retrospective comparison of results in 186 patients with LUTS of BPH is based on findings of three recently reported prospective clinical trials. All patients underwent targeted high-energy TUMT. Ninety-one patients received no further treatment (TUMT alone group), 54 an indwelling PBC for up to 1 month (TUMT + PBC group), and 41 neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment (TUMT + tamsulosin group). The International Prostate Symptom Score (IPSS), QOL score, and Qmax were determined at baseline and 2 weeks after TUMT. RESULTS: All three study groups experienced statistically significant improvements in mean IPSS and QOL score at 2 weeks versus baseline (P <0.0005). Nevertheless, the magnitude of improvement was greater in the TUMT + PBC group than the other two groups and greater in the TUMT + tamsulosin group than the TUMT alone group. A high proportion of the TUMT + PBC group (87.8%) attained a 50% or more IPSS improvement, compared with 4.5% of the TUMT alone group and none of the TUMT + tamsulosin group, and a similar pattern of between-group differences was noted with respect to the proportion of patients having 50% or more improvement in QOL score. The TUMT + PBC group was the only group to achieve significant Qmax improvement at 2 weeks compared with baseline. In the TUMT alone group, urinary retention 1 week or longer in duration occurred in 10 (11%) of 91 patients compared with 1 (2.4%) of 41 in the TUMT + tamsulosin group and none in the TUMT + PBC group. Early PBC removal was required in 11% of the TUMT + PBC group as a consequence of urinary retention secondary to clot formation or PBC migration. CONCLUSIONS: Both PBC placement and neoadjuvant and adjuvant alpha-blocker treatment are effective in alleviating symptoms and improving QOL during the acute period after TUMT. PBC usage also resulted in substantial early Qmax improvement. Either of these adjunctive modalities may be appropriate to consider in the treatment of TUMT patients during the early postprocedure recovery period.

Outcome analysis of minimally invasive treatments for benign prostatic hyperplasia.

The armamentarium of minimally invasive treatment modalities for patients with benign prostatic hyperplasia has increased steadily during the past decade. The energy sources used range from microwaves and radiofrequency waves to high-intensity focused ultrasound, with laser vaporization/coagulation/resection and electrosurgical techniques. The large amount of data available allow some conclusions to be drawn concerning the present role of the "gold standard" TURP among the minimally invasive procedures. Although the subjective response after TURP and other minimally invasive procedures is comparable, improvements of flow and urodynamic parameters usually are more pronounced after TURP. Failure rates requiring reintervention (usually TURP) are considerable. Minimally invasive procedures lead to a shift of morbidity from the intraoperative phase, which is reduced (risk of bleeding, TUR syndrome, transfusion) to the postoperative phase. This period is characterized by prolonged urinary retention (ILC, VLAP), significant dysuria (VLAP, TUVP), and nycturia. Recent advances in electrosurgical techniques, such as band TURP loops that facilitate coagulation due to the longer contact time between the electrode and the tissue, have the potential to convert TURP into a less invasive procedure. Finally, high-energy TUMT seems to offer a truly minimally invasive treatment combining efficacy and the need for topical anesthesia only. However, due to a lack of homogeneity of criteria for patient recruitment, parameters of evaluation, and adequate follow-up; accurate guidelines for appropriate patient management have not been established yet.