Quality of life and symptoms in a randomized trial of radiotherapy versus deferred treatment of localized prostate carcinoma.

BACKGROUND: Treatment of localized prostate carcinoma (LPC) using radiotherapy (RT) can induce disturbances in a patient's quality of life (QOL) and urinary and intestinal function. Late symptoms and QOL were evaluated in a randomized trial between RT and deferred treatment (DT). METHODS: Quality of life was evaluated with European Organization for Research and Treatment of Cancer's QLQ-C30 (+3) formula. Urinary and intestinal problems were evaluated with a validated symptom specific self-assessment questionnaire, QUFW94. The questionnaires were sent to 108 randomized patients with LPC and to an age-matched control group (n = 68). Mean age was 72 years. Mean total dose was 65 grays (Gy; 62.3-70 Gy). The median follow-up time from randomization was 40.6 months for the RT group and 30.4 months for the DT group. RESULTS: Social functioning was the only QOL scale in which a significant difference was found between the two patient groups and compared with the control group. Multivariate regression analysis showed that hematuria, incontinence, mucus, and planning of daily activities in response to intestinal problems caused this decrease in QOL in the RT group. A significant increase of intestinal problems was observed in the RT versus DT groups regarding mucus, stool leakage, intestinal blood, and planning of daily activity in response to intestinal problems. CONCLUSIONS: The RT patients showed increased levels of minor intestinal side effects compared with the DT patients and the controls, but the RT patients reported no decreased QOL except for decreased social functioning. This could be because this group developed coping skills or because of a low magnitude of side effects to influence the QOL.

Quantitative bone scintigraphy. A methodological evaluation in prostate cancer.

PURPOSE: To evaluate a simple method for quantification of focal activity in bone scintigraphy (BS). MATERIAL AND METHODS: The gamma camera was calibrated using a phantom. Quantitative bone scintigraphy (QBS) was performed on 11 men recently diagnosed with prostate cancer (PCa), for whom routine BS showed involvement of the skeleton. Following endocrine therapy for 4 to 8 months, a second QBS was performed. Changes in QBS values were then compared to changes in serum levels of prostate-specific antigen (PSA). RESULTS: PSA response indicating regression of PCa was accompanied by a decrease in the QBS value in 8 of the 11 patients. The overall mean error of the QBS values was 15%. CONCLUSION: QBS according to this method is a relatively simple procedure that might contribute to objective evaluation of therapeutic effects in skeletal metastases, although its validity must be tested in a larger clinical material.

After radiotherapy testosterone stimulation is unable to increase growth in the dunning R3327-PAP prostate tumour.

A study was carried out to investigate whether testosterone treatment is able to influence tumour growth in a rat prostatic adenocarcinoma previously treated with castration and high-dose fractionated irradiation. Copenhagen x Fisher rats bearing the androgen-sensitive, well-differentiated Dunning R3327-PAP tumour were castrated and thereafter treated with external beam radiation with photons from a 4-MV linear accelerator. One month after irradiation, substitution with subcutaneous testosterone was started. Tumour volumes and rat weights were monitored up to 256 days after castration, and at the end of the study a microscopic analysis of the tumours was performed. Irradiation delayed tumour growth as compared with untreated tumours. Castration delayed tumour growth, but a hormone-refractory relapse to doubled tumour volume was seen within 45 days. If testosterone was added after castration, the tumours grew rapidly. However, testosterone failed to increase tumour growth when given to rats treated with orchiectomy and irradiation. Histological examination showed that the irradiated tumours still contained tumour epithelial cells, but these cells apparently do not respond to testosterone stimulation. The well-differentiated and androgen-sensitive rat prostatic adenocarcinoma did not grow after irradiation despite stimulation with testosterone. This indicates that the malignant cells lose their androgen sensitivity after high-dose irradiation.

Predictive value of prostate-specific antigen, tumour stage and tumour grade for the outcome of bone scintigraphy in patients with newly diagnosed prostate cancer.

OBJECTIVE: In order to evaluate the negative predictive value of a low prostate-specific antigen (PSA) for a positive bone scan, we performed a retrospective study in a patient material from the Umea region in Northern Sweden. We also evaluated whether different tumour grades could influence this predictive value. MATERIAL AND METHODS: Four-hundred-and-forty-six patients of newly diagnosed prostate cancer were reviewed. We analysed different levels of PSA, tumour grade, tumour stage and combinations of these parameters for their use in making a positive bone scintigraphy (BS) prediction. RESULTS: Among 214 patients with PSA <20 ng/ml, 9 showed a positive BS. When tumours of grades 2 and 3 were excluded, the number of positive BS predictions decreased to 6. For 350 of these 446 patients, a classification according to TNM was available; 162 of these 350 had a PSA value <20 ng/ml, and when this group comprised only small and well-differentiated tumours (T1-2, G1), only one of the remaining 81 patients had a positive BS result. CONCLUSIONS: We conclude that in most patients with small and well-differentiated tumours (T1-2, G1) and PSA <20, BS staging need not be carried out.

Ureteric obstruction due to kinking of the reservoir inlet in a continent urinary reservoir.

We report a case of symptomatic intermittent upper tract obstruction in a continent urinary reservoir. The ureters were of great intraperitoneal length and were positioned in front of the mesenterium, resulting in a mobile reservoir. Only the retroperitoneal part of the ureters was dilated due to kinking in the peritoneal passage. After the ureters were shortened and reanastomosed retroperitoneally, the repeated episodes of abdominal pain and discomfort disappeared..

Effects of hCG stimulation after withdrawal of long-term oestrogen treatment in patients with prostate carcinoma.

Testosterone depletion is the keystone for therapy of patients metastic prostatic carcinoma. Our objective was to investigate Leydig cell function and testosterone levels after withdrawal of long-term endocrine treatment in patients with prostatic carcinoma. Thirteen patients with prostatic carcinoma, previously treated with oestrogens for at least 4 y, were stimulated with 5000 IU human chorionic gonadotrophin (hCG). The stimulation was performed 3-6 y after cessation of the oestrogen therapy. Serum concentrations of testosterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured before and 24 and 48 h after hCG stimulation. Before hCG stimulation all patients had low serum testosterone concentrations (mean 2.0+/-0.2 nmol/l) and 24 and 48 h after hCG stimulation the values had not significantly increased (mean 2.4+/-0.2 and 2.5+/-1.1 nmol/l, respectively). LH and FSH were within or above the normal range before but after hCG stimulation the values significantly increased. In conclusion, the study shows that the Leydig cells were unable to respond to hCG stimulation more than 3 y after cessation of oestrogen therapy. The Leydig cell function seems to be irreversibly impaired by long-term oestrogen treatment.

Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study.

PURPOSE: We compare the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1-4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective study 91 patients with clinically localized prostate cancer were, after surgical lymph node staging, randomized to receive definitive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45). Patients treated with radiotherapy alone had androgen ablation at clinical disease progression. The effects on progression-free, disease specific and overall survival rates were calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4) clinical progression was seen in 61% of the radiotherapy only patients (group 1) and in 31% of the combined treatment patients (group 2) (p = 0.005). The mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%, respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined treatment were mainly caused by lymph node positive tumors. For node negative tumors there was no significant difference in survival rates. CONCLUSIONS: The progression-free, disease specific and overall survival rates for patients with prostate cancer and pelvic lymph node involvement are significantly better after combined androgen ablation and radiotherapy than after radiotherapy alone. These results strongly suggest that early androgen deprivation is better than deferred endocrine treatment for these patients.

Cellular changes in prostatic carcinoma after treatment with orchidectomy, estramustine phosphate and medroxyprogesterone acetate.

Thirty-three patients with prostatic carcinoma were treated with either estramustine phosphate, orchidectomy or high dose medroxyprogesterone acetate. Therapy response was evaluated by cytological examination of fine needle aspiration biopsies performed before and after 6 weeks treatment. At follow-up, 11 of 14 patients treated with estramustine phosphate had regressive and/or degenerative changes, in 2 patients there were no prostatic carcinoma cells in the smears and in one there was a marked reduction of the number of tumour cells. In 7 of 10 patients treated with orchidectomy there was a marked reduction of the percentage of malignant cells while smears from 3 patients were unchanged. In the 8 patients treated with high dose medroxyprogesterone acetate the cell patterns were unmodified compared with before treatment. We conclude that, in contrast to the lack of effect of treatment with medroxyprogesterone acetate, treatment with orchidectomy and especially estramustine phosphate caused morphologic cellular changes in prostatic carcinoma.

Morbidity after preoperative radiotherapy and cystectomy in patients with bladder cancer.

The therapy-related morbidity was evaluated in 121 patients with muscle-invasive or recurrent superficial bladder cancer treated with radiotherapy and cystectomy. In 103 patients cystectomy succeeded 39-52 Gray (Gy) preoperative irradiation and in 18 patients cystectomy was done as a salvage procedure after previous full-dose radiotherapy. The overall frequency of complications was high; 71% of the patients treated with preoperative and 78% treated with full-dose radiotherapy had clinically relevant complications related to radiotherapy or surgery or both. The rate of intestinal complications was 39% for preoperative and 67% for full-dose radiotherapy. The overall mortality rate in intestinal complications was 3.3%. This study shows that the combination of radiotherapy and radical surgery in patients with bladder cancer is associated with a high rate of intestinal complications. The complications are significantly related to the irradiation dose and are long lasting and even life threatening.

Predictive value of DNA ploidy in bladder cancer treated with preoperative radiation therapy and cystectomy.

The predictive value of flow cytometric DNA analysis of cells from bladder washings was evaluated in 43 patients with muscle-invasive or recurrent superficial bladder cancer treated with preoperative radiotherapy and cystectomy. There was no correlation between ploidy status of the primary tumour and survival, neither was there any correlation between ploidy and the occurrence of residual tumour in the cystectomy specimens. Patients without residual tumours in the cystectomy specimen had significantly longer survival time than those with residual tumours. Concomitant carcinoma in situ was correlated with better survival, which is surprising, considering the malignant potential of this lesion. In this study DNA ploidy did not predict tumour response to radiotherapy nor was it of any prognostic significance.

Levels of selenium in plasma and glutathione peroxidase in erythrocytes in patients with prostate cancer or benign hyperplasia.

Plasma selenium and glutathione peroxidase in erythrocytes were analysed in a case-control study encompassing 164 cases with prostate cancer and 152 controls with benign prostate hyperplasia. Plasma selenium levels were divided into three groups; I > 1.17, II 1.00-1.17 and III < 1.00 mumol/l. For the 124 cases with no supplementary intake of selenium pills, the mean plasma selenium level was 0.99 (range 0.27-1.47) and for the corresponding 121 controls 1.08 (range 0.52-1.50) mumol/l, a difference which was significant (P = 0.0007). The three categories of selenium levels had odds ratios (OR) of 0.3 and a 95% confidence interval (CI) of 0.1-0.7 for group I, an OR of 0.6 and a CI of 0.3-1.1 for group II, and group III was used as the reference entity. No significant differences in levels of glutathione peroxidase in erythrocytes were found between cases and controls.

Lymph leakage after staging pelvic lymphadenectomy for prostatic carcinoma with and without heparin prophylaxis.

The effect of heparin prophylaxis on lymph leakage and lymphocele formation was observed in a randomized, prospective, consecutive study of 48 patients undergoing lymph node dissection for staging carcinoma of the prostate. Subcutaneous low-dose heparin was given to 24 patients, and 24 without heparin prophylaxis constituted the control group. Lymph leakage per day was significantly greater and the leakage period longer in the heparin group than in the controls. The total of leaked lymph was notably greater and the incidence of lymphocele seven times higher in the heparin group than in the controls. All lymphoceles disappeared spontaneously in the first postoperative year. The results suggest high risk of prolonged lymph leakage and of lymphocele formation when low-dose heparin prophylaxis is given to patients undergoing a staging operation for prostatic carcinoma.

Sexual function in men after radical cystectomy with or without urethrectomy.

Sexual function was evaluated in 21 patients with bladder carcinoma who had undergone radical cystectomy either with (n = 9) or without (n = 12) excision of the urethra. All patients received preoperative radiotherapy, and the cystectomy was done by a nerve-sparing surgical technique. At follow-up all patients reported normal sexual desire and tactile sexual activity. Eight of the 12 patients in whom the urethra was preserved could achieve penile erection and orgasm to tactile stimulation, and five of them had sufficient strength and duration of erection for sexual intercourse. Two of the nine patients in whom the urethra was removed-had weak erections insufficient for intercourse; three could experience orgasm. These results show that when cystectomy is done by a nerve-sparing technique and without urethrectomy there is more chance of preserving sexual function than when simultaneous urethrectomy is done.

Dose/response study of the effects of oestrogens on tumour growth and morphology in the Dunning R3327 prostatic adenocarcinoma.

The present study was undertaken to investigate to what extent the oestrogen-induced effects on growth and morphology of the Dunning R3327 rat prostatic adenocarcinoma are dose-dependent. Castrated and testosterone-supplemented rats were used in order to study effects of increasing doses of oestrogens on the tumour. It was found that the lowest dose of oestradiol-17 beta that reduced the overall growth, the volume density of the epithelium and epithelial cell area in Dunning R3327 prostatic tumours is 10 micrograms given as daily injections. Higher oestrogen doses (50 micrograms, 200 micrograms, and 500 micrograms), in addition to reducing the volume of tumour epithelium, also induced an increase of the volume density of tumour stroma. The area of stroma cell nuclei was increased by 50 micrograms and 200 micrograms oestradiol-17 beta. These observation, may indicate that the lowest effective oestrogen dose is different in the epithelium and stroma of Dunning tumours and that large doses of oestrogen stimulate the stromal compartment. This stimulatory effect did not influence the inhibitory effects seen on the overall growth of the tumour and on the tumor epithelium.

Treatment of rat prostatic adenocarcinoma with medroxyprogesterone acetate (MPA): effects on growth and morphology.

Rats bearing the Dunning R3327H prostatic carcinoma were castrated and supplemented with testosterone propionate. These rats were then treated with estradiol benzoate or medroxyprogesterone acetate alone or in combination with estradiol. During the treatment period of six weeks, the growth rate of the prostatic tumors was measured. At the end of the treatment period the morphology of the tumors was also studied. It was found that medroxyprogesterone acetate is as effective as estradiol in inhibiting the growth of the Dunning prostatic carcinoma and that the combination of medroxyprogesterone acetate and estradiol was more efficient in that respect than estradiol alone. Morphometric evaluation of the tumor epithelium and stroma showed a decrement of epithelial growth in all treatment groups, while the groups treated with medroxyprogesterone acetate, both alone or in combination with estradiol, also showed an inhibited growth of the tumor stroma. It was concluded that medroxyprogesterone acetate probably has direct inhibitory effects on prostatic tumor cells in the Dunning model and that medroxyprogesterone acetate may act in an additive manner with estradiol.

Effects of ethinyl oestradiol/polyoestradiol phosphate and estramustine phosphate on some proteins related to haemostasis in prostatic carcinoma patients.

Twenty-four previously untreated patients with carcinoma of the prostate were prospectively randomized to one of the following treatments: (1) ethinyl oestradiol combined with polyoestradiol phosphate (EE/EP); (2) estramustine phosphate (EM); (3) bilateral orchiectomy. The effects on some plasma proteins related to haemostasis were studied by measuring the concentrations of alpha-1-antitrypsin, orosomucoid, haptoglobin, antithrombin III, C1-inhibitor and von Willebrand's factor before and 3 months after the start of treatment. Orchiectomy induced a reduction of alpha-1-antitrypsin and haptoglobin, while the other studied proteins were unaffected. It was found that both EE/EP and EM treatment induced significant decreases of orosomucoid, haptoglobin, antithrombin III and C1-inhibitor, while the same treatment increased the plasma concentration of alpha-1-antitrypsin. None of these treatments showed any influence on the plasma concentration of the von Willebrand factor. No differences were observed between EE/EP and EM for any of the studied proteins, suggesting comparable oestrogenic effects of these forms of treatment in patients with prostatic carcinoma. The findings are discussed in relation to the proposed difference in thromboembolic complications between EE/EP and EM treatments of prostatic carcinoma patients.

Urinary tract calculi dissolved by means of renacidin. An experimental study.

Removal urinary tract calculi by surgery may be difficult in patients with poor health or in patients who have been operated on earlier. By means of percutaneous nephrostomy it is possible to irrigate the renal pelvis with Renacidin to dissolve calculi. Renacidin is a buffer and mainly consists of citrate and gluconate. The solution makes it possible to dissolve some calculi. This study was carried out in order to evaluate the influence of the concentration of renacidin and of the speed of the irrigation. Urinary tract calculi were obtained from five patients. The calculi were cut into 2 mm thick slices. Each slice was weighed before it was placed in a chamber for irrigation. Irrigation of the slices by means of renacidin was performed at speeds of 30, 60 or 120 ml/h. Slices wre also kept in vessels containing renacidin without replacing the fluid during the irrigation. In two series dissolution was investigated for various concentrations of renacidin. Elementary analysis using absorption and spectrophotometric techniques was performed and a qualitative evaluation of the distribution of the inorganic components was carried out using the microradiographic technique. The speed of the dissolution of urinary calculi varied between 0.43 and 7.7 mg/h. Two stones were easily dissolved (5 and 7.7 mg/h) while the three others were more resistant (0.5, 1.0 and 3.0). Diluted renacidin fluid (1:3) was less effective and reduced dissolution from 5.8 to 0.7 mg/h. The speed of the irrigation was of minor importance in the experimental situation. The dissolving effect of renacidin varied for different calculi.(ABSTRACT TRUNCATED AT 250 WORDS)

Estrogen treatment combined with castration inhibits tumor growth more effectively than castration alone in the Dunning R3327 rat prostatic adenocarcinoma.

This study was designed to investigate whether the combination of castration with estrogen treatment for 6 weeks (combined treatment) further inhibits growth of the Dunning R3327 rat prostatic adenocarcinoma as compared with castration alone. Combined treatment arrested tumor growth more effectively than castration. Combined treatment also induced morphological changes in both tumor stroma and epithelium that were not found in tumors from castrated animals. The volume density of the tumor epithelium was reduced and the volume density of the tumor stroma was increased by the combined treatment as compared with castration alone. The number of tumor epithelial cells was calculated by morphological methods: combined treatment lowered the number as compared with castration alone. The number of tumor epithelial cells was similar in castrated and intact rats. Both combined treatment and castration alone reduced tumor epithelium cell size as compared with tumors from intact rats. These findings suggest that estrogen may have direct effects on total number and function of prostatic tumor cells.