The 24-h frequency-volume chart in adults reporting no voiding complaints: defining reference values and analysing variables.

OBJECTIVE: To determine the variables (e.g. voiding frequency, voided volumes, urine production) and their mutual relationships and differences between age groups and genders, using a frequency-volume chart (FVC) in an adult population (representing all age groups) who denied having any voiding complaints. SUBJECTS AND METHODS: In all, 1152 men and women aged > 20 years completed a 24-h FVC; registration started with the first voided volume in the morning and concluded with the first voided volume the next morning. The time of voiding and volume were both recorded, and bedtime hours noted. Each participant claimed to have no voiding complaints. The statistical analysis was aimed at discerning the relationships between the FVC variables, gender and age. RESULTS: There was a linear increase in mean 24-h voiding frequency and nocturia in men, from 6.0 and 0.5 in the third decade to 8.5 and 1.6 in those aged > 70 years. Contrary to men, in women the mean 24-h frequency declined slightly in the older decades; it increased from 6.9 in the third to 8.2 in the sixth, declining to 7.8 in those aged > 70 years. Nocturia in women increased linearly, although slower than in men, from 0.7 in the third decade to 1.4 in those aged > 70 years. The mean volume/void decreased significantly in both genders, from 313 to 209 mL in men, and from 274 to 240 mL in women. The mean 24-h volume was 1718 and 1762 mL in men and women, respectively. For both genders there was a strong linear association between 24-h urine production and voided volumes. CONCLUSION: The volume/void and maximum voided volume decreased significantly with age in both sexes, but more prominently in men. As a result, in men the frequency increased with age, probably reflecting subclinical changes associated with the development of prostatic enlargement. In contrast to men the frequency in women increased initially and decreased in the older groups. A higher 24-h urine production was associated with a higher mean volume/void.

Histological grading of papillary urothelial carcinoma of the bladder: prognostic value of the 1998 WHO/ISUP classification system and comparison with conventional grading systems.

AIM: To test the prognostic value of the 1998 WHO/ISUP (World Health Organisation/International Society of Urologic Pathology) consensus classification system in Ta papillary urothelial neoplasms of the bladder. METHODS: The histological slides of 322 patients with a primary Ta tumour were classified according to the consensus classification system, and recurrence free survival (RFS) and progression free survival (PFS) were assessed for a mean follow up period of 79 months. In the same patient group, the RFS and PFS rates for the 1973 WHO grading system and a low grade/high grade system were analysed. RESULTS: Recurrent tumours were seen in all categories of the 1998 WHO/ISUP classification system and five year RFS was not significantly different between the groups (p = 0.12). The five year PFS showed a small but significant difference (p = 0.04) between papillary neoplasms of low malignant potential (PNLMP) and high grade papillary urothelial carcinomas (HGPUCs). In the 1973 WHO classification, no significant difference was found in RFS and PFS between the different grades. In the low grade/high grade classification PFS was significantly better for low grade tumours (p = 0.01). CONCLUSION: The prognostic value of the 1998 WHO/ISUP classification system is limited to predicting PFS, especially between PNLMP and HGPUC. The prognostic value of this system over other grading systems is questionable.

Abnormalities detected in metaphase chromosomes in bladder carcinoma: prognostic value and comparison with histopathological factors.

The objective of this study was to detect the incidence and prognostic value of chromosomal aberrations in metaphase chromosomes (hypodiploidy, hyperdiploidy and/or structural abnormalities) in Ta and T1 transitional cell carcinoma (TCC) of the bladder. Of 266 patients, the metaphase chromosomes of the primary tumour were studied using a direct microscopic analysis and classified into two categories: normal and abnormal. Recurrence and progression were prospectively recorded during a median follow-up period of 40 months and in a retrospective analysis compared with other prognostic factors. Chromosomal abnormalities were found in 48% of Ta tumours and in 92% of T1 tumours. In univariate analysis, chromosomal abnormalities were associated with recurrence-free survival ( P=0.03) and progression-free survival ( P=0.01). In multivariate analysis, chromosomal abnormalities (RR=1.98) and age (RR=0.64) were independent predictors of recurrence-free survival but not progression-free survival.

Laser therapy for carcinoma in situ of the penis.

PURPOSE: Carcinoma in situ of the penis, also referred to as Bowen's disease or erythroplasia of Queyrat, may lead to invasive squamous cell carcinoma. We assessed the results of laser therapy for carcinoma in situ of the penis. MATERIALS AND METHODS: From 1986 to 2000 we treated 19 patients with carcinoma in situ of the penis with the neodymium:YAG or carbon dioxide laser. Treatment was assessed retrospectively. No patient was lost to followup. RESULTS: No complications developed and cosmesis was excellent. After 2 to 4 months 3 patients (16%) received repeat treatment because of incomplete disappearance of the lesion. Mean followup was 32 months. True carcinoma in situ recurrent in 5 patients (26%) at an average followup of 25 months (range 6 to 75), while 1 had infiltrating carcinoma. All patients with carcinoma in situ underwent repeat laser treatment. CONCLUSIONS: In our experience laser therapy is appropriate initial treatment for carcinoma in situ of the penis with excellent cosmetic and functional results. This therapy is also suited for recurrence without the need for more mutilating therapy. However, the high incidence of recurrence indicates the need for careful followup and patient self-examination.

Antiandrogen monotherapy: a new form of treatment for patients with prostate cancer.

Nonsteroidal antiandrogens are generally used in conjunction with castration as combined androgen blockade. However, the changing profile of patients with prostate cancer has made monotherapy with a nonsteroidal antiandrogen an attractive alternative therapeutic approach, offering potential quality-of-life benefits over conventional treatment modalities. Of available antiandrogens, monotherapy with bicalutamide has been most extensively evaluated. Combined data from 2 studies at a median follow-up time of 6.3 years revealed no statistically significant difference in overall survival between bicalutamide 150-mg monotherapy and castration in patients with nonmetastatic locally advanced disease. In patients with metastatic disease, there was a statistically significant difference (6 weeks) in overall survival in favor of castration. Bicalutamide monotherapy is associated with significant quality-of-life benefits (sexual interest and physical capacity), with preliminary data suggesting that the risk of osteoporosis may also be reduced by bicalutamide 150-mg monotherapy compared with castration. In general, bicalutamide is well tolerated, with a predictable adverse-effect profile. Breast pain (40%) and gynecomastia (49%) are the most common adverse events seen during monotherapy with this drug. In summary, the availability of bicalutamide 150-mg monotherapy broadens treatment options for men with locally advanced prostate cancer, offering a viable and attractive alternative to castration in this patient population. Ongoing studies will determine the role of bicalutamide in the treatment of localized disease.

Early versus late androgen deprivation therapy in metastatic disease.

Patients presenting with metastatic prostatic cancer can be categorized into 3 groups. At present, most patients seen with metastases are those identified as having lymph-node disease when being assessed for curative therapy. The second group consists of patients with a high level of prostate-specific antigen, without symptoms, who are found incidentally to have asymptomatic bone metastases or metastases in soft tissue. The third group, who previously comprised about half of patients presenting with metastatic prostate cancer, are those presenting with painful metastases. There can be little doubt that most urologists will treat the second and third group of patients with hormone therapy at the outset. The question is whether the mere presence of lymph-node metastases or painless bony or soft tissue metastases justifies the side effects of long-term hormone therapy. A number of studies have shown a benefit in progression-free survival in the treatment of patients with lymph-node disease. Only 1 study has shown an advantage in overall survival. All studies of hormone therapy in asymptomatic and symptomatic metastatic disease have shown that serious complications of the disease can be avoided by offering hormonal therapy when the diagnosis is established. With the new generation of antiandrogens, differentiation therapies, and possibly alpha-reductase inhibitors, hormone therapy causes many fewer side effects than in the past and can be tolerated for longer periods of time. An aim of early hormonal therapy and its justification is a possible improvement in the quality of life of patients with metastatic prostate carcinoma, whose quantity of life cannot be lengthened.

The use of valrubicin for the chemoresection of superficial bladder cancer -- a marker lesion study.

OBJECTIVES: To assess the effect and tolerance of a 6-week course of intravesical valrubicin on a tumour intentionally left in the bladder (marker lesion) following incomplete transurethral resection of the bladder (TURBT). PATIENTS AND METHODS: In a prospective phase II study, 40 patients with refractory superficial transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent TURBT at which a tumour <1 cm in diameter was deliberately left in the bladder. They were then treated with six instillations of 800 mg valrubicin at weekly intervals. Patients were assessed three months after the initial TURBT by cystoscopy and biopsy. Patients remaining clear of disease underwent repeat cystoscopies at 3-monthly intervals until recurrence or for up 2 years. RESULTS: 21/39 (54%) of patients were found to be clinically clear of disease upon cystoscopic examination at 3 months. 18/39 (46%) of patients were considered histologically clear of bladder disease. The current estimate of the mean time to recurrence is 248 days. CONCLUSIONS: A 6-week course of intravesical valrubicin has proved effective in ablating a marker tumour left in the bladder after incomplete TURBT and in preventing or delaying recurrence of further tumours in a group of patients with previously treated superficial TCC.

Quality control of radical prostatectomy: a feasibility study.

The aim of this study was to assess whether the quality of the surgical act could be an important prognostic factor for patients undergoing radical prostatectomy. This study also aims to investigate whether the surgical quality can be assessed by any means. Questionnaires were collected from 23 different institutes including 232 radical prostatectomies (RPr) performed for T1T2 prostate cancer. Blood loss, duration of surgery, margin status, postoperative prostate specific antigen (PSA) and urinary incontinence were analysed and correlated with the yearly number of RPr performed. The mean values obtained for each parameter were very different in the various centres. The outcome in terms of tumour control and incontinence could not be related to a higher or lower number of RPr performed. Quality control of RPr is feasible on the basis of an analysis of a few parameters, such as surgical margins, postoperative PSA and incontinence, that might recognise urologists that perform better or poorer than a proposed average.

Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide.

The use, tolerability and efficacy of the non-steroidal anti-androgen nilutamide (Anandron(R)) in daily clinical practice was investigated in this 5-y project. In total 725 patients were recruited from 27 Dutch centres. The investigated population was very heterogeneous and different therapeutic options were reported. We may conclude that in general good results have been obtained, especially in first line combination therapy combined with luteinising hormone releasing hormone (LHRH) agonists. Patients with a good performance status at inclusion seem to benefit more from nilutamide combination therapy.Prostate Cancer and Prostatic Diseases (2001) 4, 112-117

Use of balloon catheters for ureteral occlusion in urinary leakage.

PURPOSE: Urinary fistula after treatment for cancer constitutes a therapeutic dilemma, especially in patients who have had various other treatments. We report on 7 patients with urinary leakage, treated conservatively with ureteric occlusion by way of percutaneous transrenal balloon catheters. MATERIALS AND METHODS: The indication for ureteral occlusion was persisting urinary leakage despite diversion by nephrostomy and drainage with atransurethral catheter. All patients had had previous treatment because of pelvic malignancy. Small Foley balloon catheters and angioplasty catheters were used. These devices were inserted percutaneously in an antegrade fashion. RESULTS: In all but 2 of the patients the leakage ceased with the aid of these devices. Insufficient ureteral occlusion necessitated unilateral uretero-cutaneostomy in 1 patient. In another patient a vesico vaginal fistula was closed surgically. The maximum duration of occlusion was 169 (mean 94, range 45-169) days, without any evidence of ureteric pressure necrosis. Despite good overall results many adjustments and replacements of catheters were necessary because of recurrent urinary leakage caused by inadequate obstruction and/or leakage of the occluding catheters. CONCLUSIONS: We conclude that long-term ureteral occlusion with percutaneous transrenal balloon catheters appears to be safe and does not result in pressure necrosis. Using this approach, urinary fistula can heal in some patients without the need for open surgery.

Chronic cystitis caused by Corynebacterium urealyticum detected by polymerase chain reaction.

The case of a 73-year-old man with chronic cystitis due to Corynebacterium urealyticum was complicated by hematuria and urinary stone formation. The diagnosis was based on an amplification product obtained using polymerase chain reaction for mycobacterial species on urine and a bladder biopsy specimen. A specific 212 bp amplification fragment that did not hybridize with a Mycobacterium-specific probe was recognized. Sequence analysis of the fragment revealed Corynebacterium urealyticum. Routine urine cultures were negative, but prolonged culture on sheep blood agar led to the isolation and identification of Corynebacterium urealyticum. Identification was confirmed by polymerase chain reaction on the colonies. The patient was treated successfully with vancomycin. Integration of molecular laboratory diagnostics with conventional microbiology and pathology was synergistic for the diagnosis.

New strategies for the treatment of hormone-independent prostate cancer.

It is quite likely that in every prostate cancer, at the start of clinical disease there are hormone-independent cells present. These cells may be sensitive to changes in the diet, to chemotherapeutic agents, to immunological agents, to the use of vaccines or may be sensitive to radiotherapy. The introduction of these non-hormonal therapies has classically been reserved for the time when the patient has exhausted all other treatment therapies and has a large tumour volume which will almost certainly not respond to such treatments. The purpose of this chapter will be to try to arrive at a more sensible definition of hormone-independent disease than has been used in the past, to outline some of the new treatment strategies and to make suggestions as to where in the natural history of the disease these would be most effectively and easily employed.Prostate Cancer and Prostatic Diseases (2000) 3, 290-295

Tailoring of hormonal therapy in prostate cancer.

With an increasing interest in the early introduction of hormonal therapy in patients who cannot be cured of their prostate cancer by radical surgery or radiotherapy, there is a need to consider the most patient-friendly, effective hormonal therapy at each stage of the disease, thereby hoping not only to improve the quantity of the patient's life but also to maintain a reasonable quality of life. With the development of new hormonal therapies such as non-steroidal androgens, LHRH-antagonists and differentiation agents, urologists need to look again at the hormonal status of their patients before prescribing an appropriate therapy. There is increasing evidence that at certain stages of the disease patients are prepared to trade off the length of life for improved quality and bearing this in mind there needs to be some substantial re-thinking over the most appropriate therapy, particularly at early stages of the patient's disease and following progression to the later stages. Prostate Cancer and Prostatic Diseases (2000) 3, 21-27

Defining an international research agenda for quality of life in men with prostate cancer.

BACKGROUND: While the traditional goal in the management of patients with prostate cancer has been to maximize survival, the recent advent of the medical outcomes movement has underscored the importance of patient-centered issues, such as health-related quality of life (HRQOL). METHODS: In this paper we present a comprehensive approach to the study of HRQOL in men with prostate cancer. We begin by defining HRQOL in general, discussing its measurement, and placing it in the context of prostate cancer. We then describe the primary goals of HRQOL research and present examples of validated instruments. We finish by proposing a quality of life research agenda for the next two decades. RESULTS: Contemporary perspectives on HRQOL are based on the World Health Organization's definition of health as not merely the absence of disease, but as a state of physical, emotional, and social well-being. HRQOL measurement must adhere to the strict methodological principles of survey psychometrics and is best accomplished with any of several validated instruments. Once collected, HRQOL information is useful for prostate cancer patients facing difficult treatment decisions. CONCLUSIONS: A solid foundation for HRQOL research has been built in early- and late-stage prostate cancer. It includes the development of new instruments and the establishment of descriptive data. This groundwork will allow investigators to address more complex research issues, such as interpreting interactions among HRQOL domains, presenting HRQOL data to future patients, optimally timing HRQOL data collection, uncovering innate and alterable factors that influence HRQOL, and exploring the intercultural nuances of HRQOL assessment.

Synergism between cisplatin and radiotherapy in an in vitro prostate tumor cell line.

BACKGROUND: A combination of local irradiation and systemic cytotoxic treatment could improve therapeutic efficacy in metastatic prostate cancer. Radiosensitization can augment the treatment response to standard doses of radiation or enable lower treatment doses to be given; thus decreasing possible side effects. Intracellular glutathione has been implicated in the mechanism of such radio- sensitizing effects. MATERIALS AND METHODS: In the present study, R3327-MATLyLu prostate tumor cells were treated with cisplatin (0.0325 microM, 0.1625 microM, 0.325 microM and control "0 microM") in combination with irradiation (2, 4, 6, 8 Gy and control "0 Gy"). The survival of clonogenic tumor cells in agar was determined. In another experiment the irradiation was carried out after a 3 hours pretreatment with cisplatin concentrations (1.63 microM, 3.25 microM, 6.5 microM and control "0 microM") both in the presence and absence of Glutathione. RESULTS: In both experimental conditions the combination of cisplatin with irradiation yielded significant supra-additive treatment effects. CONCLUSIONS: The analysis of combination treatment effects, using two different methods confirmed the existence of synergism. The presence of a high level of extracellular glutathione did not alter the radiosensitization effects observed without glutathione, suggesting that the presence of glutathione may not be a major limiting factor in the radiosensitization effects observed in these investigations.

Combination 186Re-HEDP and cisplatin supra-additive treatment effects in prostate cancer cells.

UNLABELLED: Radionuclide therapy has proven to be an efficacious palliative treatment for metastatic prostate cancer. Its potential therapeutic possibilities may be substantially increased by combining it with effective radiosensitizing drugs. METHODS: This study explores the radiosensitizing properties of cisplatin when combined with 186Re-labeled hydroxyethylidene diphosphonate (HEDP) in the treatment of R3327-MATLyLu prostate cancer cells in vitro. A concomitant incubation during 4 d, combining various concentrations of cisplatin (0, 0.42, 0.83 and 1.67 micromol/L) and 186Re-HEDP (0, 1.84 and 3.69 MBq/mL [0, 50 and 100 microCi/mL, respectively]) was followed by the determination of the cell numbers surviving and the replating of these cells in semisolid agar. RESULTS: The surviving fraction of clonogenic tumor cells after combination treatment clearly showed synergism when analyzed by a panel of three different published analytical methods. In addition, analysis of variance demonstrated a significant interaction between radionuclide therapy and cisplatin-based chemotherapy (P < 0.001). Treatment with 186Re-HEDP and cisplatin by sequential incubation yielded similar, but never superior results. CONCLUSION: It is concluded that radionuclide therapy in combination with cisplatin is able, in principle, to improve therapeutic success rate in metastatic prostate cancer in a more than additive way.

Response of PC-3 prostate cancer cells to combination therapy using irradiation with glucocorticoids or doxorubicin.

OBJECTIVES: We evaluated the effects of irradiation, doxorubicin and dexamethasone on human PC-3 prostate cancer cells, investigating whether dexamethasone and doxorubicin can alter the irradiation cytotoxicity of PC-3 cells. METHODS: We used the human PC-3 prostate cancer cells, analyzing cell growth with trypan blue exclusion, indices of the cell cycle with flow cytometry and apoptosis with flow cytometry and analysis of DNA fragmentation on simple agarose gel. RESULTS: Doxorubicin (100 nM) arrested cell cycle at the G2/M phase, decreased cell growth and produced apoptosis of PC-3 cells in a time-dependent manner. Dexamethasone (100 nM) increased the distribution of PC-3 cells at G0/G1 phase in the cell cycle, exerting an inhibitory effect on the proliferation of PC-3 cells after 48 and 72 hr, but it did not produce apoptosis. Irradiation (4 Gy) initially arrested cells at the G2/M phase in the cell cycle (24 hr) which was gradually overcome and the PC-3 cells were shifted into G0/G1 phase or apoptosis after 48 and 72 hr. Irradiation decreased the PC-3 cell growth by 40-50% after 48 and 72 hr, respectively. Treatment with doxorubicin (100 nM) for 24, 48, and 72 hr after irradiation potentiated irradiation cytotoxicity of PC-3 cells. Dexamethasone treatment 24 hr before and 24, 48 and 72 hr after irradiation increased the number of surviving PC-3 cells and partially neutralized the irradiation effects on cell cycle. CONCLUSION: Doxorubicin potentiated while dexamethasone partially reversed the irradiation cytotoxicity of PC-3 cells. These data may be of clinical importance for the treatment of hormone refractory prostate cancer.