Keywan Ghawidel

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.

Total and transition zone prostate volume and age: How do they affect the utility of PSA-based diagnostic parameters for early prostate cancer detection?

OBJECTIVES To define the role of total prostate (TP) volume, transition zone (TZ) volume, and age as determinants of the utility of prostate-specific antigen (PSA)-based diagnostic parameters for early detection of prostate cancer (PCa) in a prospective multicenter study. METHODS The study participants were 974 consecutive men with serum total PSA (tPSA) levels of 4 to 10 ng/mL who were referred for early PCa detection or lower urinary tract symptoms. All patients underwent prostate ultrasound examination and sextant biopsy with two additional TZ biopsies. In patients with negative initial biopsies, repeated biopsies were performed at 6 weeks. tPSA, the free/total PSA ratio (f/t PSA), PSA density of the TZ (PSA-TZ), PSA density (PSAD), and PSA velocity (PSAV) were determined and compared across TP volume strata of 30 cm3 or less and greater than 30 cm3, TZ volume strata of 20 cm3 or less and greater than 20 cm3, and various age groups to evaluate the need for volume and/or age-specific reference ranges. RESULTS PCa was found in 345 (35.4%) of 974 patients and benign prostatic tissue was found in 629 (64.6%) of 947 patients. Across TP volume strata, significantly higher values of tPSA (P <0.01), PSA-TZ, PSAD (P <0.001), and PSAV (P <0.05) and lower values of f/t PSA (P <0.001) were observed in patients with PCa than in those without PCa. Similar results were obtained with respect to TZ volume strata, except in the case of PSAV (P <0.05). tPSA, PSA-TZ, and PSAD were significantly higher (P <0.05) in patients with PCa than in those without PCa for all corresponding age ranges. In patients with PCa, f/t PSA was significantly lower (P <0.001) within the same age ranges. Within each group (PCa or benign), f/t PSA, PSAD, PSA-TZ, and PSAV values were unaffected by age strata. However, PSA parameters dependent on prostate volume (PSAD, PSA-TZ) were statistically lower (P <0.001) in prostates with a higher TP volume (greater than 30 cm3) and TZ volume (greater than 20 cm3); f/t PSA values were unaffected by TP and TZ volumes. CONCLUSIONS f/t PSA and PSA-TZ were the most powerful parameters to differentiate between benign prostatic tissue and PCa. f/t PSA was the sole parameter unaffected by age and prostate volume. We believe new volume-specific cutpoints, as presented in the current study, should be employed when using PSAD and PSA-TZ for the early detection of PCa.

A NOVEL INTRAURETHRAL PROSTATIC BRIDGE CATHETER FOR PREVENTION OF TEMPORARY PROSTATIC OBSTRUCTION FOLLOWING HIGH ENERGY TRANSURETHRAL MICROWAVE THERMOTHERAPY IN PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

PURPOSE We evaluate the efficacy and safety of a novel intraurethral prostatic bridge catheter in preventing temporary prostatic obstruction following targeted high energy transurethral microwave thermotherapy in patients with benign prostatic hyperplasia. MATERIALS AND METHODS A total of 54 patients with benign prostatic hyperplasia underwent high energy transurethral microwave therapy under topical urethral anesthesia followed by placement of a prostatic bridge catheter, which remained indwelling as long as 1 month (prostatic bridge catheter group). Patient evaluation included determination of peak urinary flow rate, International Prostate Symptom Score (I-PSS) and quality of life score at baseline, immediately following transurethral microwave therapy and prostatic bridge catheter placement, and periodically thereafter for 1 month. Results were retrospectively compared with those of 51 patients who underwent transurethral microwave therapy followed by standard temporary urinary catheterization, typically for 24 hours (standard catheterization group). RESULTS Immediately following transurethral microwave therapy and prostatic bridge catheter placement significant improvements (p <0.0005) were observed in mean peak flow rate, I-PSS and quality of life score of 59.3, 33.5 and 23.6%, respectively, compared with baseline values. Further improvements were noted up to 1 month, at which time mean peak flow rate, I-PSS and quality of life score had improved 79.0, 54.9 and 56.5%, respectively, versus baseline (p <0.0005). In a retrospective comparison at baseline and 14 days between the prostatic bridge catheter group and standard catheterization group mean baseline peak flow rate, I-PSS and quality of life score were similar. However, at the 14-day followup evaluation in the prostatic bridge catheter group mean peak flow rate was 101.8% higher, and I-PSS and quality of life score were 47.9 and 51.1% lower, respectively, than the corresponding values in the standard catheterization group (p <0.0005). The prostatic bridge catheter was well tolerated and remained indwelling throughout the entire 1-month followup in 48 of 54 patients (88.9%). Early prostatic bridge catheter removal was required in 3 patients (5.6%) due to urinary retention and in 3 (5.6%) due to catheter migration. CONCLUSIONS Prostatic bridge catheter placement provides an effective and well tolerated option for preventing prostatic obstruction in the acute period after transurethral microwave therapy. This approach avoids the inconvenience and infection risk of standard indwelling catheters or intermittent self-catheterization. Prostatic bridge catheter insertion and removal are rapid, facile, nontraumatic procedures. Prostatic bridge catheter may potentially be used in an array of minimally invasive procedures involving thermal treatment of the prostate gland.

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.

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia : A randomized, prospective clinical trial

OBJECTIVES Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.

Impact of chronic dialysis on serum PSA, free PSA, and free/total PSA ratio: is prostate cancer detection compromised in patients receiving long-term dialysis?

OBJECTIVES The increased incidence of malignancy (ie, prostate cancer) in patients with end-stage renal failure is well known. However, little is known of the impact of hemodialysis and various membrane types on total and free prostate-specific antigen (PSA). We prospectively studied the impact of high- and low-flux dialysis membranes and kidney function on total PSA (tPSA), free PSA (fPSA), and free/total PSA ratio (f/t PSA). METHODS A total of 149 men were included. tPSA, fPSA, and f/t PSA were measured before and immediately after dialysis with high-flux (n = 101) and low-flux (n = 48) membranes in the serum and in the dialysis ultrafiltrate. A multivariate analysis of the impact of kidney function and age on the rate of change of all parameters was performed. RESULTS Overall, a significant decrease of fPSA (from 0.49 +/- 0.3 to 0.35 +/- 0.3 ng/mL, P <0.0001) and f/t PSA (from 45 +/- 19% to 38 +/- 13%, P <0.0001) and a nonsignificant decrease in serum tPSA were observed. However, fPSA (from 0.51 +/- 0.5 to 0.27 +/- 0.3 ng/mL, P <0.0001) and f/t PSA (from 47 +/- 19% to 31 +/- 18%, P <0.0001) decreased significantly in high-flux membranes only. The ultrafiltrate contained 100% fPSA in high-flux membranes and no fPSA in low-flux membranes. Age, serum creatinine, blood urea nitrogen, and dialysis evaluation parameters (Kt/V) had no impact on correlation with changes in tPSA and fPSA. CONCLUSIONS tPSA molecules do not pass high- and low-flux membranes; fPSA passes high-flux membranes only. The nonsignificant decrease of tPSA is due to adsorption to both dialysis membranes. Although tPSA can safely be used to screen patients on dialysis, independently from the dialysis procedure and membrane, fPSA and f/t PSA are only reliable with low-flux membranes. Finally, we can state that the fPSA is most probably cleared through the kidneys by glomerular filtration.

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.

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.