Multimodal Primary Treatment of Metastatic Prostate Cancer with Androgen Deprivation and Radiation.

AIM: We combined anti-androgen therapy with radiotherapy in a first-line setting for metastatic prostate cancer aiming to cause maximal cancer-cell death to delay the emergence of castration-resistant disease. MATERIALS AND METHODS: In this non-randomized retrospective series of 46 patients, the initial median prostate-specific antigen (PSA) was 98.5 µg/l (range=6.7-15,500), median Gleason score 9 and most men had at least T3N1M1 disease. All patients received luteinizing hormone releasing hormone analog or degarelix with bicalutamide. If PSA remained above 1 µg/l, docetaxel was initiated. At PSA nadir, all patients received radical radiotherapy of the prostate. RESULTS: The median follow-up time was 4.38 years (range=0.36-11.24). Most radiotherapy-related adverse events were grade 1 and transient. There were no grade 4 events. Overall survival (OS) at 5 years was 81.3%. CONCLUSION: The feasibility and safety of aggressive multimodality treatment were good resulting in an excellent median OS of 8.35 years.

Comparison of intermittent and continuous androgen deprivation and quality of life between patients with locally advanced and patients with metastatic prostate cancer: a post hoc analysis of the randomized FinnProstate Study VII.

OBJECTIVE: The aim of the study was to compare intermittent (IAD) and continuous (CAD) androgen deprivation therapy (ADT) between locally advanced (M0) and metastatic (M1) prostate cancer, and the effect of ADT on the quality of life. MATERIAL AND METHODS: In total, 852 men with advanced prostate cancer were enrolled to receive goserelin acetate for 24 weeks. Of these, 554 patients whose prostate-specific antigen (PSA) decreased to less than 10 ng/ml or by at least 50% (<20 ng/ml at baseline) were randomized to IAD or CAD. In the IAD arm, ADT was resumed for at least 24 weeks whenever PSA increased to greater than 20 ng/ml or above baseline. RESULTS: Median follow-up time was 65 months. Median times from randomization to progression, death, prostate cancer death and treatment failure in M0 and M1 patients were 46.8 and 21.4, 57.6 and 40.3, 59.5 and 40.7, and 41.9 and 20.0 months, respectively (p < 0.001). No significant differences emerged between IAD and CAD. ADT showed a beneficial effect on pain, activity limitation and social functioning in M1 patients, and a deleterious effect on physical capacity in M0 patients and on sexual functioning in both groups. IAD offered extra benefit for activity limitation, social functioning and recovery of sexual functioning. CONCLUSIONS: IAD is as efficient as CAD in treatment of locally advanced and metastatic prostate cancer. ADT improves quality of life in M1 patients, with IAD offering extra benefit.

Effect of intervention on decision making of treatment for disease progression, prostate-specific antigen biochemical failure and prostate cancer death.

BACKGROUND: Patient preference for the choice of treatment modality for prostate cancer has increasingly gained attention. OBJECTIVE: To assess the impact of client-oriented decision on long-term mortality, disease progression and biochemical failure compared with standard treatment protocol (TP). METHODS: With data from a Finnish multicentre, randomized controlled trial with two arms [104 in the enhanced patient participation (EPP) arm and 106 in the TP arm], disease-specific and disease-free survival, biochemical failure with elevated prostate-specific antigen (PSA) level and disease progression were compared between the two arms using Wilcoxon test and also Cox proportional hazards regression model. RESULTS: Patients in the EPP arm had a higher risk of death by 37% [HR, 1.37 (0.87-2.17)] compared with those in the TP arm. Patients in the EPP arm were at increased risk of having biochemical failure by 14% [HR, 1.14 (0.72-1.79)] and for having disease progression by 2% [HR, 1.02 (0.61-1.70)] compared with those in the TP arm. All the differences were non-significant. CONCLUSIONS: Patients actively involved in the choice of treatment had higher risk of prostate cancer death but only slightly increased risk of biochemical failure and clinical disease progression. These findings would provide a good reference when patient autonomy for the choice of treatment modality is addressed.

Advanced prostate cancer treated with intermittent or continuous androgen deprivation in the randomised FinnProstate Study VII: quality of life and adverse effects.

BACKGROUND: Intermittent dosing may reduce the adverse events (AEs) of androgen-deprivation therapy (ADT). OBJECTIVE: To compare intermittent androgen deprivation (IAD) and continuous androgen deprivation (CAD) with regard to health-related quality of life (QoL). DESIGN, SETTING, AND PARTICIPANTS: A total of 852 men with advanced prostate cancer (PCa) were enrolled to receive goserelin acetate 3.6 mg every 28 d for 24 wk. A total of 554 patients whose prostate-specific antigen (PSA) decreased to <10 ng/ml or by ≥50% (<20 ng/ml at baseline) were randomised to IAD or CAD. INTERVENTION: In the IAD arm, ADT was resumed for at least 24 wk whenever PSA increased >20 ng/ml or above baseline. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: QoL was monitored with a validated Cleary 30-item questionnaire and analysed by the Mann-Whitney U test, 0.5 standard deviation rule, and repeated measures analysis of variance. AEs and adverse drug reactions (ADRs) were analysed by the chi-square test. RESULTS AND LIMITATIONS: Median follow-up was 65 mo. Significant differences in QoL emerged in activity limitation, physical capacity, and sexual functioning, favouring IAD. No significant differences emerged in the prevalence of AEs: 87 patients in the IAD arm (31.8%) and 95 in the CAD arm (33.9%) had cardiovascular (CV) AEs (p=0.59), with 25 (9.1%) and 29 (10.4%) withdrawn (p=0.62), and 21 (7.7%) and 24 (8.6%) dying because of a CV event (p=0.70), respectively; bone fractures occurred in 19 (6.9%) and 15 (5.4%) patients (p=0.44), respectively. Hot flushes or night sweats were the most common ADRs (47.1% vs 50.4%; p=0.44). Erectile dysfunction (15.7% vs 7.9%; p=0.042) and depressed mood (2.2 vs 0%; p=0.032) were more common in the IAD arm. CONCLUSIONS: IAD showed benefits in the treatment of advanced PCa with respect to QoL. The prevalence of AEs was not significantly lower with IAD. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00293670.

The FinnProstate Study VII: intermittent versus continuous androgen deprivation in patients with advanced prostate cancer.

PURPOSE: We conducted a randomized trial to compare intermittent and continuous androgen deprivation in patients with advanced prostate cancer. We studied time to progression, overall and prostate cancer specific survival, and time to treatment failure. MATERIALS AND METHODS: Between May 1997 and February 2003, 852 men with locally advanced or metastatic prostate cancer were enrolled to receive androgen deprivation therapy for 24 weeks. Patients in whom prostate specific antigen decreased to less than 10 ng/ml, or by 50% or more if less than 20 ng/ml at baseline, were randomized to intermittent or continuous androgen deprivation. In the intermittent therapy arm androgen deprivation therapy was withdrawn and resumed again for at least 24 weeks based mainly on prostate specific antigen decrease and increase. RESULTS: There were 298 patients who did not meet the randomization criteria. The remaining 554 patients were randomized, with 274 (49.5%) to intermittent androgen deprivation and 280 (50.5%) to the continuous androgen deprivation arm. Median followup was 65.0 months. Of these patients 392 (71%) died, including 186 (68%) in the intermittent androgen deprivation arm and 206 (74%) in the continuous androgen deprivation arm (p=0.12). There were 248 prostate cancer deaths, comprised of 117 (43%) in the intermittent androgen deprivation and 131 (47%) in the continuous androgen deprivation arm (p=0.29). Median times from randomization to progression were 34.5 and 30.2 months in the intermittent androgen deprivation and continuous androgen deprivation arms, respectively. Median times to death (all cause) were 45.2 and 45.7 months, to prostate cancer death 45.2 and 44.3 months, and to treatment failure 29.9 and 30.5 months, respectively. CONCLUSIONS: Intermittent androgen deprivation is a feasible, efficient and safe method to treat advanced prostate cancer compared with continuous androgen deprivation.

The proportion of free PSA and upgrading of biopsy Gleason score after radical prostatectomy.

INTRODUCTION: Upgrading of biopsy Gleason score (GS) after radical prostatectomy (RP) to GS >or=7 is common in patients with low-grade prostate cancer in biopsy. We evaluated whether a low proportion of free PSA (%fPSA) and total PSA (tPSA) predict significant upgrading after RP. PATIENTS AND METHODS: 122 patients with biopsy GS 5 or 6 prostate cancer and a tPSA <10 ng/ml who underwent RP in our academic center were included in the study. The utility of prebiopsy %fPSA and tPSA as predictors of significant upgrading was evaluated. RESULTS: Among patients undergoing RP, upgrading to GS >or=7 was found in 61 of 122 (50%) patients. A low %fPSA was a predictor of significant upgrading of tumors with biopsy GS 5 or 6 prostate cancer in patients with tPSA <10 ng/ml. CONCLUSIONS: Our results suggest that the selection of prostate cancer patients for active surveillance or re-biopsy may be improved by using %fPSA as a predictor of significant upgrading.

Prostate cancer and PSA among statin users in the Finnish prostate cancer screening trial.

Decreased risk of advanced prostate cancer has been reported among men using statins. However, the evidence on overall prostate cancer risk is conflicting. We compared the relative risk between current users and non-users of statins or other cholesterol-lowering medications in a population undergoing systematical prostate cancer screening. The study cohort comprised of 23,320 men participating in the screening arm of the Finnish prostate cancer screening trial during 1996-2004. Information on medication use was obtained from a comprehensive national prescription database. Cox proportional hazards regression was used to calculate multivariable adjusted hazard ratios (HRs) for prostate cancer. Serum prostate-specific antigen (PSA) level was compared between current users and non-users of cholesterol-lowering drugs. Compared with medication non-users, the overall prostate cancer incidence was decreased among statin users [HR 0.75, 95% confidence interval (CI) 0.63-0.89]. The inverse association was dose-dependent with cumulative amount of statin use, and strongest for low-grade and early stage tumors. The incidence was nonsignificantly lower also among users of other types of cholesterol-lowering drugs (HR 0.62, 95% CI 0.28-1.38), but without dose-dependence. Age-adjusted median serum PSA tended to be lower among users of cholesterol-lowering drugs, but the relative risk decrease among statin users was not related to decreased PSA. Overall incidence of prostate cancer was lowered among statin users when bias due to differential PSA testing between medication users and non-users was eliminated by systematical prostate cancer screening. Cholesterol-lowering with statins seems beneficial for prostate cancer prevention.

Biological aggressiveness of prostate cancer in the Finnish screening trial.

Prostate cancer aggressiveness was evaluated based on pathologic characterization of cases detected in the Finnish prostate cancer screening trial. The trial population consists of 80,458 men aged 55-67 years. A total of 32,000 men were randomized to the screening arm. The remaining 48,000 men formed the control arm. The interval cases and cancers among nonparticipants and in the control arm were identified from the Finnish Cancer Registry. Random samples were selected from screen-detected cases (126 of 543 in the first and 133 of 508 in the second round) and control arm cancers (133 out of 863), in addition to all 92 interval cancers and 106 cases among nonparticipants. All the biopsies were regraded according to the Gleason system. The expression of the proliferation antigen Ki-67 was determined in 479 cases (72%). More than half of the tumors diagnosed in the first round of screening were high-grade cancers (Gleason 7 or higher). In the second round, the proportion of low-grade cancers increased from 47% to 70%. Cancers in the screening arm were more commonly focal and fewer bilateral cancers were detected. The cancers among nonparticipants were the most aggressive group. The aggressiveness of the interval cancers was between the cancers detected in the first and the second round. Our results indicate that prostate cancers detected through screening are less biologically aggressive. This was most notable after the first screening round. Nonparticipants had more aggressive cancers.

Finnish multicenter study comparing intermittent to continuous androgen deprivation for advanced prostate cancer: interim analysis of prognostic markers affecting initial response to androgen deprivation.

PURPOSE: Intermittent androgen deprivation has been proposed to prolong hormone sensitivity and improve quality of life in patients with advanced prostate cancer. The FinnProstate Study VII has been performed to identify patients who might benefit from intermittent androgen deprivation. In this interim analysis we evaluated which prognostic markers affect the initial response to androgen deprivation therapy. MATERIALS AND METHODS: A total of 856 men with locally advanced or metastatic prostate cancer were enrolled and given androgen deprivation therapy for 24 weeks to ensure hormone sensitivity. Patients with hormone sensitive prostate cancer were randomized 1:1 to continuous androgen deprivation or intermittent androgen deprivation. The randomization criteria were prostate specific antigen decrease to less than 10 ng/ml or by more than 50% if less than 20 ng/ml at baseline. RESULTS: There were 292 patients (34%) who did not meet the randomization criteria (group 1). The remaining 564 patients (66%) were randomized to intermittent androgen deprivation or continuous androgen deprivation (group 2). Mean prostate specific antigen (834 vs 151 ng/ml), mean alkaline phosphatase (793 vs 292 IU/l), proportion of T4 tumors (37% vs 24%), poorly differentiated cancers (39% vs 26%), metastatic disease (82% vs 51%) and number of skeletal hot spots in M1 disease (more than 5 hot spots 72% vs 42%) were significantly higher in group 1 than in group 2. CONCLUSIONS: Patients with the most advanced prostate cancer and poorest prognosis do not show adequate biochemical prostate specific antigen response to androgen deprivation therapy but should be assessed for eligibility to receive nonendocrine treatment.

Laparoscopic radical prostatectomy: surgical, oncological and functional outcomes.

OBJECTIVE: To report the first results of laparoscopic radical prostatectomy (LRP) at our institution. MATERIAL AND METHODS: The surgical, functional and oncological outcomes of all patients who underwent LRP at Helsinki University Central Hospital between May 2002 and May 2006 were prospectively evaluated. The first eight patients were operated transperitoneally and the next 72 extraperitoneally. RESULTS: The mean operative time was 328+/-73 min (range 210-510 min). The mean estimated blood loss was 769+/-906 ml (range 50-5500 ml), and 18 patients (22.5%) had transfusions. The mean catheterization time was 13.2+/-4.0 days (range 9-35 days). Mean hospital stay was 5.7+/-3.1 days (range 3-15 days). Nineteen patients (23.8%) had perioperative complications. The conversion rate to open surgery was 11.3% and 6.3% required an immediate re-operation. Three anastomotic strictures (5.7%) and two cases of ileus (3.8%) were observed. The cancer was intracapsular (pT1-2) in 68 patients (85.0%) and extracapsular (pT3-4) in 12 (15.0%). Positive surgical margins were noted in 20 patients (25.0%) in total: 17.6% of pT1-2 cases and 66.7% of pT3-4 cases. Prostate-specific antigen recurrence (> or =0.2 ng/ml) was noted in 5/53 patients (9.4%), who were followed for >12 months. The continence rate (no daily pad use) was 86.8% and the potency rate was 34.6% at 12 months. CONCLUSIONS: The surgical, functional and oncological results of our first LRPs compare fairly well with the early experience of others. LRP is feasible outside high-volume centers but the learning curve is expected to be long.

Adenocarcinoma in isolated rectal bladder after treatment of bladder exstrophy.

We report the first Finnish patient with carcinoma in an augmented intestinal bladder, where urine and stools are not in contact. The patient had undergone rectal bladder reconstruction at the age of 2 years because of bladder exstrophy. When the patient was aged 46 years, a 2-cm, papillar, well-differentiated adenocarcinoma was detected and removed, preserving the rectal bladder.

Treatment of metastatic renal cancer with capsid-modified oncolytic adenoviruses.

Renal cancer is a common and deadly disease that lacks curative treatments when metastatic. Here, we have used oncolytic adenoviruses, a promising developmental approach whose safety has recently been validated in clinical trials. Although preliminary clinical efficacy data exist for selected tumor types, potency has generally been less than impressive. One important reason may be that expression of the primary receptor, coxsackie-adenovirus receptor, is often low on many or most advanced tumors, although not evaluated in detail with renal cancer. Here, we tested if fluorescence-assisted cell sorting could be used to predict efficacy of a panel of infectivity-enhanced capsid-modified marker gene expressing adenoviruses in renal cancer cell lines, clinical specimens, and subcutaneous and orthotopic murine models of peritoneally metastatic renal cell cancer. The respective selectively oncolytic adenoviruses were tested for killing of tumor cells in these models, and biodistribution after locoregional delivery was evaluated. In vivo replication was analyzed with noninvasive imaging. Ad5/3-Delta24, Ad5-Delta24RGD, and Ad5.pK7-Delta24 significantly increased survival of mice compared with mock or wild-type virus and 50% of Ad5/3-Delta24 treated mice were alive at 320 days. Because renal tumors are often highly vascularized, we investigated if results could be further improved by adding bevacizumab, a humanized antivascular endothelial growth factor antibody. The combination was well tolerated but did not improve survival, suggesting that the agents may be best used in sequence instead of together. These results set the stage for clinical testing of oncolytic adenoviruses for treatment of metastatic renal cancer currently lacking other treatment options.

Treatment of prostate cancer with Ad5/3Delta24hCG allows non-invasive detection of the magnitude and persistence of virus replication in vivo.

Hormone refractory metastatic prostate cancer is a deadly disease that currently lacks curative treatments. Conditionally replicating adenoviruses (CRAds) are promising new agents against cancer due to their innate capability to cause oncolysis of tumor cells. Their antitumor effect is determined in part by their capacity for infecting cancer cells. However, the respective primary receptor, the coxsackie-adenovirus receptor (CAR), is variably expressed in many cancer types. We created Ad5/3Delta24hCG, a novel CRAd retargeted to the adenovirus serotype 3 receptor, which has been reported to be highly expressed in tumors. Furthermore, we added a transgene for the beta-chain of human chorionic gonadotropin (hCGbeta), whose expression was tightly coupled to virus replication. Ad5/3Delta24hCG was found effective in killing prostate cancer cells, and oncolysis was seen in concordance with hCGbeta production. In a s.c. in vivo model of hormone refractory prostate cancer, Ad5/3Delta24hCG treatment resulted in statistically significant tumor growth inhibition. Moreover, i.v. injection of Ad5/3Delta24hCG prolonged the survival of mice with hormone refractory prostate cancer metastatic to the lung. Detection of hCGbeta in serum samples confirmed viral replication in vivo. Infection of human clinical samples of cancerous and normal prostatic tissue resulted in effective hCGbeta production in cancer tissue, whereas it remained low in nonmalignant tissue, suggesting cancer-specific replication. These results suggest that Ad5/3Delta24hCG is a potent virus for the treatment of hormone refractory prostate cancer in vitro and in vivo. These preclinical data set the stage for translation into clinical studies.

Sexual function of LUTS patients before and after neodymium laser prostatectomy and transurethral resection of prostate. A prospective, randomized trial.

OBJECTIVE: To assess and compare the sexual function of patients undergoing transurethral resection of the prostate (TURP) or Nd:YAG laser treatment for lower urinary tract symptoms (LUTS) caused by obstructing benign prostatic hyperplasia (BPH). PATIENTS AND METHODS: 98 LUTS patients with urodynamically confirmed bladder outlet obstruction were recruited. Patients were randomised to TURP and laser treatment, which was further divided to contact and hybrid treatments according to prostate size. The sexual function at baseline and at 1 year postoperatively was assessed from the Danish Prostate Symptom Score Sexual Function Questionnaire (DanPSS Sex) items concerned with erectile stiffness, ejaculatory volume and pain or discomfort on ejaculation. RESULTS: The sexual function data at 1 year was available for 83 patients. At baseline, a high prevalence of erectile dysfunction (86%), ejaculatory volume change (83%) and pain or discomfort on ejaculation (26%) was observed and considered problematic by 79%, 63% and 100% of men, respectively. An increase of total impotence in the TURP group was observed (p = 0.046). TURP decreased or totally eradicated the amount of ejaculate, which was the only difference found between the study groups (p < 0.001). Both laser and TURP treatments improved pain or discomfort on ejaculation. CONCLUSIONS: The prevalence of sexual dysfunction in patients with symptomatic infravesical obstruction caused by BPH is high and perceived mostly as bothersome. TURP, Nd:YAG contact or hybrid laser treatments did not increase erectile dysfunction but improved pain or discomfort on ejaculation. The only significant difference between these treatments in respect to sexual function was a higher incidence of decreased or absent ejaculate after TURP.

Long-term results of contact laser versus transurethral resection of the prostate in the treatment of benign prostatic hyperplasia with small or moderately enlarged prostates.

OBJECTIVE: To evaluate the long-term results of contact laser vaporization (CLV) of the prostate and transurethral resection of the prostate (TURP) in patients with symptomatic bladder outflow obstruction (BOO) caused by benign prostatic hyperplasia (BPH) with prostates smaller than 40 ml. MATERIAL AND METHODS: A total of 52 patients with lower urinary tract symptoms (LUTS) and urodynamically confirmed BOO caused by BPH with glands smaller than 40 ml were treated by means of CLV or TURP in a randomized trial. Changes in symptom score, urodynamics and prostate volume were evaluated during a 4-year follow-up period. RESULTS: A total of 42 (81%) of the patients were available for review at 4 years. The re-operation rate was 1/26 for each treatment. A sustained improvement in median Danish Prostate Symptom Score was seen in the laser group from 18 (range 5-54) to 5 (0-34) and in the TURP group from 18 (4-46) to 4 (0-18) (p<0.001 for both). A sustained improvement in maximum urinary flow rate was also seen in the laser group from 8.3 (4.8-19.6) ml/s to 14.3 (10.1-33.6) ml/s (p<0.001) and in the TURP group from 8.6 (5.0-15.9) ml/s to 16.1 (7.7-39.6) ml/s (p<0.01), without differences between the study groups. Median detrusor pressure at maximum urinary flow rate decreased significantly after both treatments, in the CLV group from 64 (32-112) cmH2O to 38 (18-65) cmH2O and in the TURP group from 57 (40-137) cmH2O to 28 (9-44) cmH2O (p<0.001 for both), and at 48 months was significantly higher in the laser group (p<0.01). At 4 years, 7/22 (32%) of the laser patients and 2/20 (10%) of the TURP patients were urodynamically obstructed. Post-void residual at 48 months was significantly lower in the TURP group than in the CLV group. Median prostate volume was smaller after TURP at 6 and 48 months (p<0.05). CONCLUSIONS: Long-term data of CLV and TURP treatments for BPH with small or moderately enlarged prostates indicate no significant difference in the relief of symptoms or in the rate of re-operations. However, the number of patients in this study was small and consequently the power to detect differences between the study groups was low. Regarding most objective outcome parameters, long-term follow-up revealed a slight advantage of TURP over CLV.

Patients with acute flank pain: comparison of MR urography with unenhanced helical CT.

PURPOSE: To compare unenhanced helical computed tomography (CT) and magnetic resonance (MR) urography, by using T2-weighted and contrast material-enhanced T1-weighted imaging to examine patients with acute flank pain, with reference to excretory urography and final clinical diagnosis. MATERIALS AND METHODS: Forty-nine patients underwent CT, MR urography (with T2-weighted and gadopentetate dimeglumine-enhanced T1-weighted sequences), and excretory urography. CT and MR urographic findings were evaluated separately and independently by two radiologists each (CT, observers A and B; MR urography, observers C and D) for the presence, cause, level, and degree of obstruction. The final conclusive diagnosis was based on the combination of excretory urographic, clinical, and interventional results. RESULTS: At final diagnosis, 32 (65%) patients were found to have ureteral stones causing unilateral obstruction. In ureteral stone detection, the sensitivity and specificity of CT were 90.6% (29 of 32 patients) and 100.0% (17 of 17 patients), respectively (observer A) and 90.6% (29 of 32 patients) and 94.1% (16 of 17 patients), respectively (observer B), while those of MR urography were 93.8% (30 of 32 patients) and 100.0% (17 of 17 patients), respectively (observer C) and 100.0% (32 of 32 patients) and 100.0% (17 of 17 patients), respectively (observer D). Spearman correlation coefficients for stone size at CT were 0.76 (P <.001) and 0.75 (P <.001) and at MR urography, 0.49 (P =.005) and 0.51 (P =.004). CONCLUSION: In routine clinical practice, CT is the modality of choice in the evaluation of patients with acute flank pain. MR urography is an accurate and suitable alternative imaging technique in selected patients.

The fluorescence biodistribution and kinetics of aminolevulinic acid induced protoporphyrin IX in the bladder of a rat model with orthotopic urothelial carcinoma.

PURPOSE: Photodynamic therapy is an alternative intravesical therapy modality for superficial bladder cancer. Aminolevulinic acid (ALA) induces the production of the endogenous photosensitizer protoporphyrin IX (PpIX). We compared intravenous versus intravesical administration of ALA and established the proper timing and dose of ALA for photodynamic therapy. To characterize the distribution of ALA in rat bladder tumor and normal bladder layers a cooled charge coupled device camera was used. MATERIALS AND METHODS: A total of 40 female Fisher F344 rats were used as test animals, including 36 inoculated with AY-27 tumor cells intravesically. PpIX accumulation was investigated by fluorescence microscopy comparing 100 and 300 mg./kg. intravenous administration with a 100 mg./ml. intravesical dose of ALA. Three areas of urothelium, submucosa and muscularis of the bladder wall were chosen for analysis. The software used allowed semiquantitative analysis by calculating the mean fluorescence count plus or minus standard error of mean within any chosen area on the fluorescence image. RESULTS: In this study the highest fluorescence difference in PpIX accumulation in tumor and the normal epithelium to the muscularis layer was achieved at 2 hours with intravenous administration (7:1 to 50:1). The highest absolute fluorescence levels were observed at 2 hours with the 100 mg./kg. intravenous dose and at 4 hours with the higher 300 mg./kg. dose. The difference in fluorescence intensity in tumor tissue to normal urothelium was 2:1 to 3:1 at 2 hours. At 4 hours it was less than 2:1. After intravesical administration no difference in PpIX accumulation in tumor and normal urothelium was observed. However, there was a 7:1 ratio in regard to the muscularis layer at 4 hours. CONCLUSIONS: According to the results of this study a difference in PpIX accumulation in urothelial carcinoma or normal urothelium and the muscular layer of the bladder can be achieved by each route of ALA administration. Although intravesical installation provided tumor and normal urothelium labeling comparable to the intravenous route, it lost the selectivity of PpIX accumulation in tumor and normal urothelium. The effect of this finding on clinical therapy results remains to be resolved in the future.

Parenteral estrogen versus combined androgen deprivation in the treatment of metastatic prostatic cancer -- Scandinavian Prostatic Cancer Group (SPCG) Study No. 5.

OBJECTIVE: In the mid-1980s, interest in parenteral estrogen therapy for prostate cancer was renewed when it was found that it influenced liver metabolism only marginally and had very few cardiovascular side-effects. In this study high-dose polyestradiol phosphate (PEP; Estradurin) was compared to combined androgen deprivation (CAD) for the treatment of patients with metastatic prostate cancer. The aim of the study was to compare anticancer efficacy and adverse events, especially cardiovascular side-effects. MATERIAL AND METHODS: A total of 917 patients with T0-4, NX, M1, G1-3 prostate cancer and an Eastern Cooperative Oncology Group performance status of 0-2 were randomized to treatment with either PEP 240 mg i.m. twice a month for 2 months and thereafter once a month or flutamide (Eulexin) 250 mg t.i.d. per os in combination with either triptorelin (Decapeptyl) 3.75 mg per month i.m. or, on an optional basis, bilateral orchidectomy. A total of 556 patients had died at the time of this analysis. RESULTS: There was no difference between the treatment arms in terms of time to biochemical or clinical progression and overall or disease-specific survival. There was no increase in cardiovascular mortality in the PEP arm. The PEP group had a higher prevalence of cardiovascular disease prior to the study and a significantly higher incidence of non-fatal ischemic heart events and heart decompensation during the study. CONCLUSIONS: PEP has an equal anticancer efficacy to CAD and does not increase cardiovascular mortality. Final evaluation of cardiovascular morbidity is awaiting further analysis and follow-up. PEP is considerably cheaper than CAD.