Use of urinary hydroxyproline excretion as a marker of bone metastases in prostatic cancer (1)

Twenty-four hour urinary hydroxyproline and urinary hydroxyproline creatinine ratio was measured without prior dietary restriction in 24 patients with prostatic cancer and 16 patients with benign prostatic hypertrophy. Both were elevated in patients with prostatic cancer with active bone metastases compared to the values of prostatic cancer without bone metastasis and benign prostatic hypertrophy. In these cases, the values of urinary hydroxyproline creatinine ratio were more reliable. The results show that urinary hydroxyproline creatinine ratio is a very sensitive indicator of active bone metastases of prostatic cancer without dietary restriction.     

Serial spot hydroxyproline/creatinine ratios in metastatic prostatic cancer

Analysis of urinary hydroxyproline levels offers a marker to monitor osseous involvement in patients with metastatic malignancies. Such a marker is needed in patients with prostatic cancer when bone metastases predominate. Thirty-two men with stage D2 prostatic cancer were monitored by bone scan, acid and alkaline phosphatase values, and urinary hydroxyproline, beginning from 4 to 36 months after initiation of hormonal manipulation and/or systemic chemotherapy. In patients with disease progression determined by bone scan serial urinary hydroxyproline values progressively increased and were significantly elevated compared to urinary values obtained from patients with a stable or improving scan (p less than 0.001). Simultaneous alkaline phosphatase determinations showed less significant differences between patient groups. Acid phosphatase did not reliably indicate osseous response to therapy. These data suggest that urinary hydroxyproline values are predictive as an early objective sign of osseous response in patients receiving therapy for stage D2 prostatic cancer.     

Comparative performance of three radioimmunoassays for prostatic acid phosphatase

Three commercial radioimmunoassays and one enzymatic assay for prostatic acid phosphatase (PAP) have been tested on 122 patients to determine their relative specificity, sensitivity, and diagnostic value. Each of the three radioimmunoassays was found to have special merits. For distinguishing Stage IV prostatic cancer from normal patients without prostatic disease, the Smith Kline (SKF) and New England Nuclear (NEN) assays provide more significant differences. The SKF test also best distinguishes all stages of prostatic cancer from benign prostatic hyperplasia (BPH), but is inferior to the Malinckrodt (MAL) assay for contrasting Stage IV prostatic cancer from BPH. Values obtained with the NEN assay best distinguish the stages of prostatic cancer. Only with the MAL assay are significantly higher PAP values obtained in patients with metastases to bone than those without positive bone scans. Viewed from the point of sensitivity, the SKF assay proves best at all levels of specificity examined in detecting all stages (I-IV), and Stage IV prostatic cancer. By none of the assays can estrogenized Stage III and IV cancer patients be distinguished from those not on estrogen.     

Responses to the antagonistic analog of LH-RH (SB-75, cetrorelix) in patients with benign prostatic hyperplasia and prostatic cancer

Among new highly potent antagonistic analogs of luteinizing hormone-releasing hormone (LH-RH), containing neutral hydrophilic D-ureidoalkyl amino acids such as D-Cit and D-Hci at position 6 and free of edematogenic and anaphylactoid reactions, Ac-D-Nal(2)¹, D-Ph(4Cl)², D-Pa1(3)³, D-Cit⁶, D-Ala¹⁰ (LH-RH) (SB-75; Cetrorelix) was shown to be one of the most powerful. In this trial, we evaluated the response to 500 μg SB-75 given every 12 hr subcutaneously (sc) for 4 weeks in 11 patients with benign prostatic hyperplasia (BPH), and 6 weeks in 6 prostatic cancer patients (2 stage C, 4 stage D2). In patients with BPH presenting with prostatism and urinary outflow obstruction, there was a noticeable clinical improvement after the first week of SB-75 administration. This improvement continued during the course of treatment. Before therapy with SB-75, the serum levels of prostate-specific antigen (PSA) (6.73 ± 1.46 ng/ml), acid phosphatases, total (12.67 ± 1.15 U/l), and prostatic (2.27 ± 0.34 U/l), were mildly elevated, but declined to normal values at 4 weeks: (2.13 ± 0.59 ng/ml; P < 0.01), (7.68 ± 0.89 U/l; P < 0.01), and (1.39 ± 0.18 U/l; P < 0.01), respectively. Mean prostatic volume assessed by ultrasonography showed a significant decrease in all patients from 67.84 ± 8.86 to 37.92 ± 8.52 cm³; P < 0.01, which represents a reduction of 44%. In patients with prostate cancer, after the first week of therapy with SB-75, we observed a significant decrease in bone pain, relief in urinary outflow obstruction, and reversal of the signs of prostatism. Subjective improvement continued during the following weeks of treatment, so that the patients no longer needed analgesics. PSA, acid, and alkaline phosphatases gradually fell, achieving nearly normal values at 6 weeks. Initial serum testosterone levels in BPH and prostatic cancer patients were within normal limits, but during treatment with the antagonistic analog SB-75, fell to castration values. A major fall in free testosterone levels was observed after the first dose; the maximal inhibition was seen after 6-12 hr, with a simultaneous decrease in levels of both gonadotropins. Our results show that antagonist 58-75 can be safely administered for prolonged periods of time. The rapid shrinkage of the prostate and concomitant improvement in obstructive symptoms of prostatism obtained with antagonistic analog SB-75 in patients with BPH may decrease the morbidity of prostatic surgery and offer a therapeutic alternative in men who are considered poor surgical risks. Antagonist SB-75 could also be useful for the treatment of prostatic cancer, but further studies are required. © 1994 Wiley-Liss, Inc.     

Evaluation of Serum Arginase Activity in Benign Prostatic Hypertrophy and Prostatic Cancer

Activities of arginase, prostatic acid phosphatase (PAP) and prostate specific antigen (PSA) were determined in sera of healthy male controls, benign prostatic hypertrophy (BPH) and prostatic cancer patients. Serum arginase activity in the cancer group (22.8±11.6 U/l) was significantly lower than in both the control (33.64±16.19 U/l) and the BPH group (58.8±11.6 U/l) (p<0.001, respectively), while the BPH group had significantly higher levels compared to the controls (p<0.05). However, serum arginase levels in all groups had no statistically significant correlation with PAP and PSA. Serum arginase activity correlated inversely with the Gleason grades. These results suggest that serum arginase assay may be used for the pretreatment evaluation of patients with prostatic diseases.     

Excretion of three major prostatic secretory proteins in the urine of normal men and patients with benign prostatic hypertrophy or prostate cancer

We have studied the mode of excretion of three prostatic secretory proteins, namely acid phosphatase (PAP), prostate-specific antigen (PSA) and beta-inhibin, in the urine of normal adult men, and we have determined the urinary levels of these proteins in men with benign prostatic hypertrophy (BPH) or adenocarcinoma. The output of the three proteins was highly variable during the day. In order to minimize these variations, 24-hour urine samples were collected thereafter. Our study showed that PAP concentrations in 50% of men with or without symptomatic BPH were similar to those of normal young men. In the remaining 50%, PAP was undetectable. In contrast, average PSA and beta-inhibin concentrations were higher in patients with BPH than in young men (p less than 0.05). The three markers were decreased or nondetectable in about half of the patients with untreated prostatic cancer. This phenomenon was even more pronounced in patients receiving hormonal treatment (castration or diethylstilbestrol). However, some of these patients still excreted normal amounts of PAP, PSA, and beta-inhibin. Urinary and serum PAP levels showed no correlation. These results indicate that urinary prostatic markers provide an easy means to study the behavior of the primary prostatic tumor. This information may be of potential value since it is not obtained with serum markers which originate mostly from metastatic cells.     

Bone-Turnover Metabolites as Clinical Markers of Bone Metastasis in Patients with Prostatic Carcinoma

Background : Candidate markers of prostatic metastases to bone, urinary deoxypyridinoline, serum carboxy-terminal propeptide of type 1 procollagen (P1CP), and pyridinoline cross-linked carboxy-terminal telopeptide of type 1 collagen (1CTP), were measured to evaluate their prognostic efficacy.
Methods : Urinary levels (mean ± SD) of deoxypyridinoline were measured by a competitive immunoassay, and serum levels of P1CP and 1CTP were measured by radioimmunoassay in 30 patients with benign prostatic hyperplasia, 18 patients with prostatic carcinoma without bone metastases, and 27 patients with prostatic carcinoma and bone metastases.
Results : Urinary concentrations of deoxypyridinoline (pmol/μmol creatinine) in patients with prostatic carcinoma and bone metastases (10.4 ± 7.7) were significantly higher than those in similar patients without bone metastases (4.3 ± 1.3) and those in patients with benign prostatic hyperplasia (3.8 ± 1.2). Serum levels of P1CP and 1CTP (ng/mL) in patients with prostatic carcinoma and bone metastases (262.6 ± 188.7 and 10.3 ± 9.5, respectively) were significantly higher than those in similar patients without bone metastases (118.1 ± 30.2 and 4.3 ± 1.4, respectively) and those in patients with benign prostatic hyperplasia (93.9 + 25.1 and 3.3 ± 1.1, respectively). Serial measurements of urinary deoxypyridinoline and serum P1CP and 1CTP were correlated with a positive response to treatment (reduced measurements) and with the clinical progression of disease (increased measurements) before detection of new bone lesions by bone scintigram.
Conclusion :Urinary deoxypyridinoline, serum P1CP, and serum 1CTP should be useful markers in confirming and monitoring prostatic carcinoma metastases to bone.     

A study on usefulness of the crude nuclear DHT measurement in prostatic cancer patients

The nuclear and crude nuclear 5 alpha-dihydrotestosterone (DHT) levels were measured in patients with benign prostatic hypertrophy (BPH) and prostatic cancer (PC). In the fundamental study using BPH tissues, nuclear DHT levels were not influenced by the treatment for nuclear purification such as DTT, Triton X-100 or DNase I. The correlation between DHT levels and androgen receptor contents was found in only the crude nuclear salt extractable fractions (r = 0.748, p less than 0.01). In the relation of DHT levels to prostatic cancer patients, crude nuclear salt extractable and salt resistant DHT in both the low grade and in early stage group were significantly higher than those in the high grade and in advanced stage. Moreover, DHT levels in the both crude nuclear salt extractable and salt resistant fractions were below 5 pg/mg protein in all of clinical non-responders to endocrine therapy, and the total crude nuclear DHT, the sum of the crude extractable and salt resistant DHT, was below 10 pg/mg protein in all of the non-responders to endocrine therapy. When the relation between the total crude nuclear DHT level and the clinical course of 34 prostatic cancer patients followed for over 12 months was studied, the elevated DHT group (over 20 pg/ml protein) responded to endocrine therapy and experienced long-term remissions, but the low DHT group (below 10 pg/ml protein) did not respond to endocrine therapy. Therefore, it is suggested that the total crude nuclear DHT levels were appropriate biochemical indicators for androgen dependency in prostatic cancer patients.     

Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were evaluated in 23 patients with benign prostatic hyperplasia (BPH), 115 with prostatic carcinoma, of whom 21 had bone metastasis, and in 16 age-matched control subjects. RESULTS: Patients with newly diagnosed prostate cancer and bone metastasis had a higher urinary excretion of DPD, and a higher serum PSA and ALP than had patients with BPH and those with prostate cancer but no metastasis. Receiver operating curve analysis for PSA, ALP and DPD showed a significant discriminating ability for positive and negative bone scans (P = 0.0684). However, from logistic regression of the combinations, only serum ALP was a significant independent predictor of bone metastasis in patients with prostate cancer. CONCLUSION: Serum ALP or urinary DPD are the best predictors of bone metastasis in patients with prostate cancer; further studies with more patients are required.     

Positive random iliac bone biopsy in advanced prostatic cancer

Forty-one patients with biopsy proved prostatic cancer and with biopsy proved bone metastases were retrospectively evaluated. In 16 per cent of the patients, bone biopsy was positive in spite of negative skeletal survey. Positive skeletal survey and increased serum acid phosphatase levels were found in 78 per cent of the patients, although bone marrow acid phosphatase was elevated in all patients. The determination of bone marrow acid phosphatase was found to be the most sensitive parameter in detection of bone metastases in patients with advanced prostatic cancer.     

Hyperparathyroidism in metastases of prostatic carcinoma: a biochemical, hormonal and histomorphometric study

Secondary hyperparathyroidism can develop as a result of bone metastases from prostatic cancer, but this has not been studied from the multiple aspects of biochemistry, hormonal status and histomorphometry. In 20 patients with stage-D prostatic cancer, a transiliac bone biopsy was performed for histomorphometric study. In all of them, molecular parathormone (PTH-M) and osteocalcin were determined by radioimmunoassay together with other parameters considered to be biological markers of bone remodelling. Of these 20 patients, only 2 (10%) had elevated PTH-M (240 +/- 20.6 pmol/l), differing significantly from the other 18 (58.6 +/- 11.7 pmol/l) and from controls (60.4 +/- 7.2 pmol/l). In the high PTH-M patients, corrected calcium was low (7.8 +/- 0.4 mg/dl) as compared to normal PTH-M patients (9.2 +/- 0.5 mg/dl, p less than 0.001), and this was also the case for serum phosphorus (2.2 +/- 0.6 vs. 3.2 +/- 0.3 and 3.4 +/- 0.4 mg/dl, respectively p less than 0.001). Alkaline phosphatase was raised in the patient groups as compared to controls (p less than 0.001) and was higher in the high PTH-M group (362 +/- 58 vs. 224 +/- 62 U/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of prostate-specific antigen in untreated prostatic carcinoma

A study was performed on 290 men to compare the level of serum prostate-specific antigen (PSA) in controls, patients with benign prostatic hyperplasia (BPH) and patients with prostatic cancer. The upper limit of normal was 5.0 micrograms/l as determined in 110 elderly hospitalized males (mean age 62 years) without urological complaints. Of the 106 patients with BPH, 33% had raised values above 5.0 micrograms/l. Values above 10 micrograms/l were found in 18 BPH patients. A positive correlation was found between prostate volume (grams of tissue removed during transurethral resection) and preoperative PSA levels (r = 0.55, n = 106, p less than 0.001). PSA levels above 10 micrograms/l were found in 4% of BPH patients with a prostate volume of less than 20 g (n = 54), in contrast with 45% of patients with a prostate volume above 40 g (n = 20). The sensitivity of this PSA assay (cutoff level 10 micrograms/l) as established in 74 prostate carcinoma patients was 31% for category T0 (n = 13), 56% for category T1-2 (n = 16), 75% for category T3-4 (n = 20) and 100% for category M1 or N1-4 (n = 25). In an earlier study prostatic acid phosphatase (PAP) was measured in these same samples. PSA appeared to be much more sensitive than PAP. Seventeen of the 74 prostatic carcinoma patients (23%) had normal PAP levels but their PSA values were raised above 10 micrograms/l, while in only 2 patients an increased PAP level was combined with a normal PSA.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of 25 and 75 mg/day naftopidil for lower urinary tract symptoms associated with benign prostatic hyperplasia: A prospective, randomized controlled study

BACKGROUND: The present study investigated the efficacy, safety, and utility of starting an alpha(1d)-selective antagonist, naftopidil, at 75 or 25 mg/day in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH). METHODS: In this prospective comparative study, the subjects comprised 153 patients with LUTS associated with BPH. Patients were randomized to receive either 25 mg/day (Group LD) or 75 mg/day (Group HD) of naftopidil for 4 weeks. The lower urinary tract disease symptom score (LUTDSS), the International Prostate Symptom Score (IPSS), the Quality of life assessment index, the maximum flow rate (Q(max)), and the residual urine volume were compared between the groups. RESULTS: In both groups, the LUTDSS and the IPSS were significantly improved at the endpoint and no significant intergroup differences were identified. However, the improvement in the Q(max) was significantly better for Group HD than for Group LD. The overall efficacy did not differ significantly between the groups. The degree of improvement in voiding symptoms and LUTDSS among patients with moderate symptoms was significantly greater for Group HD than for Group LD. The frequency of adverse reactions did not differ significantly between the groups. CONCLUSIONS: Starting administration at 75 mg/day rather than 25mg/day is helpful for LUTS associated with BPH for patients with moderate symptoms, particularly in improving voiding symptoms. The 75 mg/day administration was considered to be a recommendable therapeutic dose in some patients.     

Anatomoclinical and biologic correlations in prostatic pathology. Apropos of 150 case reports

The authors analyzed 150 patient files (16 controls with no prostatic pathology, 96 patients with benign prostatic hypertrophy (BPH), 38 prostate cancer patients) in an attempt to answer three questions: how should borderline values of PSA be interpreted in patients with BPH; is there a correlation between the Gleason grade and PSA levels in prostate cancer? Should both PSA and PAP concentrations be assayed? All patients underwent digital rectal examination and transrectal ultrasonography (TU), and were assayed for PSA and PAP. All prostate cancer patients had a bone scintigraphy (Bs). In view of the correlation coefficient of 0.391 (p less than 0.001), it can be affirmed that PSA and weight are linearly correlated in BPH (5 g BPH = 1 ng/ml PSA). This lower value of PSA is due to the overevaluation of prostate weight by TU. In contrast, the authors did not find any correlation between the PSA level and the Gleason grade in prostate cancer patients with a negative bone scintiscan. Finally, the sensitivity of PSA was markedly better than that of PAP (75% vs 50%), and no PSA false negative error was corrected by the PAP value.     

Radioimmunoassayable prostate-specific acid phosphatase in peripheral and bone marrow sera compared in diagnosis of prostatic cancer patients

Measurements of human prostate-specific acid phosphatase by radioimmunoassay in peripheral and bone marrow sera were compared. We studied 20 patients with benign prostatic hyperplasia, 27 with untreated prostatic cancer without bone metastases and 11 with metastases, in addition to 7 with cancer treated by hormonal therapy. The prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum samples were equal and did not exceed the upper limit of our health-associated reference interval, 2.8 microgram. per 1. (mean plus 2 standard deviations) in patients with prostatic hyperplasia. Of 27 prostatic cancer patients without bone metastases the concentration of prostate-specific acid phosphatase was elevated in the peripheral sera of 20 and in the bone marrow sera of 21, and 21 had an extracapsular tumor (stage T3 to T4). Prostate-specific acid phosphatase concentrations were elevated in peripheral and bone marrow serum specimens of all 11 patients with metastases and bone marrow cytology studies were positive in 2. There was no difference in prostate-specific acid phosphatase concentrations in peripheral and bone marrow serum specimens from prostatic cancer patients undergoing hormonal treatment. We conclude that the use of bone marrow serum for the measurement of radioimmunoassayable prostate-specific acid phosphatase in prostatic cancer patients does not provide any further information in regard to the detection of prostatic cancer compared to the use of peripheral serum specimens. Falsely positive findings in bone marrow specimens were not observed with the method used.     

血清前列腺特异抗原测定的临床意义

以12例前列腺癌、102例前列腺良性增生(BPH)、16例直肠指检(DRE)异常、5例前列腺炎及30例正常男性为对象,用酶免法测定血清前列腺特异抗原(Prostate specific antigen,PSA)浓度,用放免法测定其中37例。前列腺癌的PSA浓度明显高于BPH(P<0.01),PSA对前列腺癌诊断的敏感性为91.7％。DRE异常者大于BPH(P<0.05),低于前列腺癌(P<0.01)。BPH高于正常对照(P<0.01)。前列腺切除术后一日的PSA高于术前(P<0.01),术后6～8日同术前无显著性差异(P>0.05)。70岁以上高于70岁以下(P<0.05)。PSA>10ng/ml时酶免检测值低于放免法(0.010.05)。单纯PSA升高并不能说明任何特异性病理过程,前列腺癌的诊断,应结合PSA系列测定值及DRE和经直肠B超(TRUS)来综合分析。     

Significance of prostatic acid phosphatase, gamma-seminoprotein and prostatic specific antigen in the urine. First report: the measurement of PAP, gamma-Sm and PA in the urine of patients with prostatic diseases]

To study the significance of prostatic acid phosphatase (PAP), gamma-seminoprotein (gamma-Sm) and prostatic specific antigen (PA) in urine, we have determined the urinary levels of these proteins in women and infants, in patients without prostatic disease, in patients with benign prostatic hypertrophy, and in patients with prostatic adenocarcinoma. Women and infants were found to excrete little PAP (27.9 +/- 4.8 ng/mg) and undetectable levels of gamma-Sm except one case, and undetectable levels of PA in the urine. The excretion of PAP in patients with prostatic carcinoma who were either castrated, or treated with endocrine therapy was lower than the levels in women and infants, or the levels in patients without prostatic diseases, or the levels in patients with BPH. Urinary excretion levels of gamma-Sm and PA were undetectable in the patients with well-controlled prostatic carcinoma. The present study suggests that the determination of PAP, gamma-Sm and PA in the urine of patients with prostatic carcinoma may become a useful tool for monitoring of the primary locus of the carcinoma, but additional assays of urinary PAP, gamma-Sm and PA should be measured at regular intervals to be concluded.     

Urinary Pyridinoline and Deoxypyridinoline as Potential Markers of Bone Metastasis in Patients with Prostate Cancer

Purpose

The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome.

Materials and Methods

Urinary pyridinoline, urinary deoxypyridinoline, serum alkaline phosphatase and serum osteocalcin were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine.

Results

Levels of pyridinoline and deoxypyridinoline in urine, and the level of alkaline phosphatase in serum from patients with bone metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serum osteocalcin levels failed to separate the 3 groups. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy.

Conclusions

Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.     

Clinical effects of beta-sitosterol (phytosterol) on benign prostatic hyperplasia: preliminary study

Phytosterol derived from plants has long been used for the medical treatment of benign prostatic hyperplasia (BPH) in Europe but not in Japan. The efficacy of phytosterol was evaluated in patients with manifestations of urinary outlet obstruction caused by BPH. Phytosterol containing 180 mg of sitosterol per day was given to 12 patients with BPH in two or three divided doses for three months. The symptoms were assessed monthly using the International Prostate Symptom Score (IPSS) and quality-of-life (QOL) score while the objective findings including the urinary flow, prostatic volume, and residual urine volume were assessed after three months of treatment of BPH. The IPSS and QOL scores showed significant improvement (p < 0.05), and the peak flow rate and residual urine volume showed slight but not significant improvement.     

Additional effect of propiverine for naftopidil-resistant nocturia in the patient with benign prostate hypertrophy

The efficacy and safety of additional administration of propiverine were prospectively studied for naftopidil-resistant nocturia in patients with benign prostatic hypertrophy (BPH). Patients of 50 years and over with BPH who experienced nocturia twice a night or more and an overall International Prostate Symptom Score (IPSS) of 8 or more were first administered naftopidil (50 or 75 mg/day) for 4 weeks. Thirty subjects who did not show improvement in nocturia and requested further treatment were enrolled in the present study. Propiverine was then administered concomitantly 10 mg/day for 8 weeks. Significant improvement was observed with additional propiverine in the frequency of nocturia on voiding diary, total IPSS, voiding symptom, storage symptom and nocturnal voiding scores. No significant change was observed in the peak urinary flow rate (Qmax), mean urinary flow rate (Qave), voided urine volume, or residual urine volume. Adverse events were dysuria (2 cases), increased residual urine (6 cases), weak urine flow (1 case), thirsty (2 cases), angular cheilitis (1 case). Administration of propiverine was suspended in 7 subjects, 1 following dysuria and 6 following increased residual urine volume. The suspension of propiverine following increased residual urine volume was significantly more prevalent in subjects with pretreatment Qmax values of less than 10 ml/second or in subjects whose prostate specific antigen (PSA) levels were 2 ng/ml or more. In conclusion, the results indicate that additional administration of propiverine may be useful for the patients with BPH who have naftopidil-resistant nocturia. However, caution must be exercised regarding Qmax and PSA levels.