Bernd Bursa

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.

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.

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.

Cell-surface matrix proteins and sialic acids in cell-crystal adhesion; the effect of crystal binding on the viability of human CAKI-1 renal epithelial cells

To investigate the role of sialic acids and cellular matrix proteins as crystal‐binding molecules in human calcium‐oxalate nephrolithiasis.

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.

Minimal invasive Therapiealternativen für das lokalisierte Prostatakarzinom

Über die Behandlung des klinisch lokalisierten Prostatakarzinom wird nach wie vor viel diskutiert. Die Behandlungsmöglichkeiten erstrecken sich von den agressiven kurativen Therapien bis zur engmaschigen Kontrolle ohne in die Krankheit einzugreifen (“Watchfull Waiting”). Normalerweise wird jungen Patienten mit einer Lebenserwartung von mehr als 10 Jahren die radikale Prostatektomie (RPE) [7, 8, 19] oder die Bestrahlung vorgeschlagen. Bei älteren Männern, insbesondere bei solchen mit einer “low grade”-/“low Stage”-Erkrankung, fällt die Entscheidung aufgrund der höheren Komorbidität schwerer. Da aufgrund dieser Komorbidität die Durchführung der aggressiven Therapien deutlich erschwert ist, gelangen die minimal invasiven Therapien, die, sei es durch interstitielle Bestrahlung, Kryo- oder thermale Destruktion zur lokalen Zerstörung führen, zu neuer Bedeutung [3, 4, 5, 12].