Radiotherapy of localised prostate cancer. Analysis of late treatment complications. A prospective study.

PURPOSE: To describe the late side-effects of radical radiotherapy of prostatic carcinoma and to analyse how pretreatment and treatment-related factors contribute to the toxicity. MATERIALS AND METHODS: 184 patients have regularly been followed after terminated radical external beam radiotherapy treatment (70 Gy) for a mean of 46 (range 24-96) months. For registration of toxicity a modified RTOG scale was used. The Cox regression model was used for multivariate analysis. RESULTS: 37% of the patients had no late side-effects at all. Mild complications were reported by 53%, mainly gastrointestinal (42%) and urogenital (23%). A persistent improvement of the mild toxicity was seen in nearly half of the patients with gastrointestinal or nocturnal frequency side-effects. Only 16 (9%) patients had moderate or severe complications. The multivariate analysis revealed that the risk of posttreatment complications was strongly correlated to pretreatment presence of symptoms from the organs at risk. Posttreatment complications presenting first 3 years after irradiation were rare. CONCLUSIONS: Radical external beam radiotherapy (70 Gy) can be given with a low risk of severe complications. It appears reasonable to assume that the risk can be further reduced by excluding patients with gastrointestinal and urinary tract disease or symptoms.

Irradiation of localized prostatic carcinoma with a combination of high dose rate iridium-192 brachytherapy and external beam radiotherapy with three target definitions and dose levels inside the prostate gland.

PURPOSE: Localized prostate cancer was treated with combined external beam radiotherapy and high dose rate Ir-192 brachytherapy with the purpose of a high dose. The technical aspects of a modified treatment are described. METHODS: The brachytherapy was given in two sessions preceded and succeeded by external beam radiation. The radioactive source was temporarily implanted by a remote afterloading device through six to 15 needles inserted transperineally guided by transrectal ultrasound. The entire prostate gland was included in the clinical target volume. The urethra and the tumour volume could be defined and irradiated to different dose levels in more than 90% of the patients. RESULTS: Fifty-four patients were treated. The total dose to the prostate was approximately 70 Gy and to the tumour volume 80 Gy. By calculating the corresponding dose given by 2.0 Gy fractions, considering the radiobiology by using the LQ formula and assuming an alpha/beta value for prostate tissue of 10, the dose to the prostate was approximately 84 Gy and to the tumour volume 112 Gy. For the late effects to the urethra an alpha/beta value of 3 was used, which corresponds to 85 Gy. The brachytherapy could be given with accuracy except when the dorsal border of the prostate was concave. The dose distribution then tended to be less satisfactory. Post-treatment calculations showed that the maximum dose to the rectum was 67 Gy (radiobiologically corrected to 88 Gy), given in a small volume. The early side effects from the brachytherapy were minimal. The treatment could not be performed as intended in four patients; three patients had a narrow pelvis and in one patient the prostate was unusually resilient, preventing the needles from being positioned properly. CONCLUSIONS: This modification of a previously reported brachytherapy technique for prostate carcinoma permits a high radiation dose to the tumour and to the prostate gland, which ultimately may improve local control.

Combined treatment with temporary short-term high dose rate iridium-192 brachytherapy and external beam radiotherapy for irradiation of localized prostatic carcinoma.

PURPOSE: To evaluate the treatment outcome after radical radiotherapy of localized prostate cancer in 50 patients (38 patients with stage T1-2 and 12 patients with stage T3) after a median follow-up time of 45 months (range 18-92 months). METHODS: The treatment was given by combination of external beam radiotherapy (50 Gy) and brachytherapy (2 x 10 Gy). The brachytherapy was given using TRUS-guided percutaneously inserted temporary needles with a high dose rate remote afterloading technique with Ir-192 as the radionuclide source. Three target definitions and dose levels inside the prostate gland were used. Local control was evaluated by digital rectal examination, TRUS-guided biopsies and serum PSA evaluations. RESULTS: Clinical and biopsy verified local control was achieved in 48 of the 50 (96%) patients; for stage T1-2 in 37 of 38 (97%) patients and for stage T3 in 11 of 12 (92%) patients. A posttreatment serum PSA level < or =1.0 ng/ml was seen in 42 (84%) patients, values from >1.0 to < or =2.0 ng/ml were seen in four (8%) patients and values exceeding 2.0 were seen in four (8%) patients. The late toxicity was minimal. CONCLUSION: The local control results and the minimal toxicity after the combined radiotherapy treatment are promising. However, long term results are necessary before general use.

The analgesic efficacy of clodronate compared with placebo in patients with painful bone metastases from prostatic cancer.

Fifty-five patients with hormone refractory prostate cancer and painful bone metastases were randomised either to placebo or to clodronate 300 mg i.v. for 3 days, followed by oral clodronate 3200 mg for four weeks. Pain intensity was assessed using Visual Analogue Scales (VAS). Mean overall pain as well as mean pain during the best and worst periods were recorded. Forty-six patients were evaluable for efficacy. No significant differences were found between the two treatments. As regards mean worst pain a substantial numerical fall was registered for the treatment group, 21 mm, but the improvement was not significant compared to that of the placebo group. This was probably due to the limited number of patients (the study was prematurely ended due to problems recruiting patients). In conclusion, no significant differences were found between the treatment arm and the controls, in contrast to results from previous studies. Possible explanations are that the doses in this study were generally lower than in previous studies, the mean baseline pain was substantially lower and that the current study was placebocontrolled. Our data indicate that if clodronate is to be used for the alleviation of bone pain in prostate cancer, patients with high baseline should be selected and high intravenous doses should be given at start of the treatment.

Early complications and survival following short-term palliative radiotherapy in invasive bladder carcinoma.

PURPOSE: We studied the early side effects and survival rates after short-term radiotherapy (7 Gy. 3 times or 5 Gy. 4 times) in patients with muscle invasive bladder carcinoma. MATERIALS AND METHODS: Between 1981 and 1992, 96 patients (median age 80 years) were treated. Followup was complete until 1994 or death. RESULTS: Early side effects caused the hospitalization of 22 patients and may have contributed to the death of 5 elderly patients. Median survival for patients with stages T2M0, T3M0, T4M0 and T2 to 4M+ disease was 27 months, 6.3 months, 5.6 months and 2.9 months, respectively. CONCLUSIONS: Short-term radiotherapy is of doubtful benefit to elderly patients with advanced bladder carcinoma and may even be harmful.

Measurement of quality of life in localized prostatic cancer patients treated with radiotherapy. Development of a prostate cancer-specific module supplementing the EORTC QLQ-C30.

The purpose of this study was to construct a multidimensional self-administered quality of life questionnaire specific to prostate cancer within the EORTC framework and to test its applicability, clinical relevance and psychometry. A proposed prostate cancer-specific module and the standardized EORTC QLQ-C30 version 1.0 were tested in 192 post-irradiated patients. Psychometric analyses comprised item convergent and discriminant validity for scaling success, analysis of the internal consistency of the multi-item scales and the validity of the scales. The clinical relevance was explored by correlation analysis including disease and treatment related parameters. The minimum psychometric criteria were met. The measurements revealed problem areas in sexuality with a mean score of 54 (SD = 33) on a 0-100 scale, and in bowel functioning, scoring 25 on average (SD = 17). Urinary complaints only reached a mean score of 6 (SD = 19). Compared to earlier measurements on untreated or irradiated localized cancer patients using the same core questionnaire, the physical and psychological scales showed higher values and the symptom scales lower symptom burden. The constructed questionnaire seems applicable and clinically relevant. The psychometric analysis revealed a few items to be revised. Patients with localized prostatic carcinoma treated with radiotherapy have a high quality of life compared to patients with localized cancer of other origin.

Quality of life in patients with prostatic cancer: results from a Swedish population study.

PURPOSE: We evaluated a prostate cancer-specific module in an unselected patient population. MATERIALS AND METHODS: A population study design was used to confirm the psychometric properties and clinical relevance of a prostate cancer-specific module, supplementing the standardized EORTC QLQ-C30 in Sweden. The study sample comprised 1,138 patients (81% response rate) examined by a mailout/mailback procedure 1.5 to 3.5 years after diagnosis. The standardized multitrait analysis method estimated the internal consistency and convergent and discriminant validity of 3 multi-item scales on sexuality, urinary symptoms and bowel symptoms. Confirmation of prostate-specific scales by disease stage and treatment used principal components analysis. The clinical relevance was tested by correlation analysis including disease and treatment-related parameters. RESULTS: Convergent and discriminant validity of all 3 prostate-specific scales was confirmed. The internal consistency was satisfactory for the sexuality and urinary scales (alpha 0.92 and 0.76, respectively), while the bowel scale failed to reach the alpha level of 0.70 required for group comparisons. The former scales showed invariance over all principal components analyses of subgroups (disease stage and treatment). The latter scale comprised differing numbers of items in the subgroup analyses, suggesting the use of single items at present. Descriptive data of the core and module questionnaires by disease and treatment-related parameters confirmed their interpretability and thus their clinical usefulness. CONCLUSIONS: The presented self-report questionnaire technique has great potential to inform clinicians about the quality of life in patients suffering from prostate cancer.

Primary small cell carcinoma of the bladder: a report of 25 cases.

Primary small cell carcinoma of the bladder is a rare condition with approximately 100 cases reported to date. An incidence of 0.7% small cell carcinoma was found in a total series of bladder tumors diagnosed in Western Sweden during a 2-year period. We describe 22 patients with primary small cell carcinoma followed to death or for at least 6 years. Three additional cases were diagnosed at autopsy. Of 18 patients with stages T2M0 to T4M0 cancer treated with locoregional therapy 5 (28%) had no evidence of disease after a median observation of 10 years (range 6 to 18) and 13 died of disease after 0.5 to 19 months (median 7.3). Two patients with metastatic disease were treated with systemic chemotherapy but died within 15 months. Two patients died shortly after the diagnostic biopsy. Our study and a review of the literature indicate that primary small cell carcinoma of the bladder is less aggressive than its pulmonary counterpart and that some patients can be cured by transurethral resection, or partial or radical cystectomy combined with radiotherapy.

Primary signet ring cell carcinoma of the bladder: a report on 10 cases.

Primary signet ring cell cancer of the urinary bladder is a rare tumour with some 70 cases reported to date. We report on ten additional cases with long-term follow-up. All 713 primary bladder tumours in western Sweden diagnosed during a 2-year period were prospectively registered and followed and all the histopathological material reviewed. A clinical and histopathological review of 816 bladder tumours from the files of the Oncology Clinic treated between 1962 and 1989 was performed. An incidence of primary signet ring cell carcinoma of 0.6% was found. Three out of five patients who were worked up as a result of an occasional episode of macroscopic haematuria were tumour-free 2, 5 and 14 years, respectively, after radical transurethral resection. Seven patients died of the disease after 5-26 (median 19) months. Our study and a review of the literature indicate that the majority of patients with primary signet ring cell carcinomas are diagnosed at an advanced stage and survival is poor. However, some patients with small tumours at diagnosis were tumour-free after transurethral resection. Radiotherapy was ineffective in most cases. Systemic chemotherapy is of no benefit.

Micropapillary bladder carcinoma: a clinicopathological study of 20 cases.

PURPOSE: Micropapillary bladder carcinoma is rare, with only 18 cases reported to date. We report 20 additional cases with long-term followup. MATERIALS AND METHODS: A total of 680 patients with an initial diagnosis of bladder carcinoma in western Sweden in 1987 and 1989 were prospectively registered. The clinical records of all 816 patients with bladder cancer treated at Sahlgrenska University Hospital with external beam irradiation between 1962 and 1989 were reviewed. The histopathological material was reviewed and immuno-histochemical analyses were performed on 20 cases identified with micropapillary bladder carcinoma. RESULTS: The incidence of micropapillary bladder carcinoma was 0.7%. Mean patient age at diagnosis was 69 years (range 45 to 82) and the male-to-female ratio was 2.3:1. All but 5 patients had stage T3a disease or higher. There was no difference in stage or prognosis between the 5 prospectively identified patients and those treated with external beam irradiation. Only 2 patients had micropapillary bladder carcinoma as the only pattern, while 1 had 10% and the remainder had 20 to 95% micropapillary bladder carcinoma. Transitional cell carcinoma was noted in 17 patients and 5 had areas of gland forming adenocarcinoma. Carcinoma in situ was noted in 13 patients and 15 had lymphatic invasion. Only 5 patients survived 5 years, 1 of whom died of bladder cancer after 7 years. Radiation and chemotherapy did not seem to be effective. CONCLUSIONS: The light microscopic appearance, which is strikingly similar to ovarian papillary serous carcinoma, and immunohistochemical staining pattern lend some support to the theory that micropapillary bladder carcinoma is a variant of adenocarcinoma. Since even the focal presence of micropapillary bladder carcinoma is associated with a poor prognosis, recognition of this entity is important. Due to its rarity, the optimal treatment of micropapillary bladder carcinoma needs to be determined in a multicenter study.

Bladder carcinoma with lymphoepithelioma-like differentiation: a report of 9 cases.

PURPOSE: Lymphoepithelioma-like carcinoma of the bladder is rare with only 14 cases reported to date. We report 9 additional cases with long-term followup. MATERIALS AND METHODS: All 713 patients with an initial diagnosis of bladder tumor in western Sweden from 1987 through 1988 were prospectively registered and followed. A clinical and histopathological review was performed on 816 bladder tumors from the files of the oncology department treated between 1962 and 1989. RESULTS: Of 9 patients with stages T2M0-T3M0 cancer treated with locoregional therapy 6 with either pure or predominant lymphoepithelioma-like carcinoma pattern had no evidence of disease after a median observation of 4 years (range 1 to 18) and 3 with focal lymphoepithelioma-like carcinoma pattern died of disease after 9 to 68 months. CONCLUSIONS: Lymphoepithelioma-like carcinoma is diagnosed in less advanced stages and has a more favorable long-term prognosis than other types of undifferentiated invasive carcinomas of the bladder. Our data and review of the literature suggest that lymphoepithelioma-like carcinoma should be treated stage by stage like other bladder carcinomas.

Long-term followup of a bladder carcinoma cohort: questionable value of radical radiotherapy.

PURPOSE: We studied the outcome of radical radiotherapy for bladder carcinoma in all patients from a well-defined region. MATERIALS AND METHODS: All 701 cases with a new bladder carcinoma between 1987 and 1988 in Western Sweden were prospectively documented and followed until 1994. Between 1987 and 1994, 74 of the 701 patients (mean age 73 years, range 54 to 88) were treated with external beam radiotherapy (60 Gy. or more). RESULTS: At least 84% of the patients had persistent tumor, a local recurrence or a symptomatic contracted bladder after external beam radiotherapy. Seven patients (9.5%) died of early or late treatment related complications. Of only 8 long-term survivors 6 had undergone radical transurethral resection before external beam radiotherapy. CONCLUSIONS: Full dose external beam radiotherapy in patients with bladder carcinoma was associated with high local recurrence and serious complication rates. It must be questioned whether elderly patients actually benefit from full dose radiotherapy.

Analysis of the local control in lymph-node staged localized prostate cancer treated by external beam radiotherapy, assessed by digital rectal examination, serum prostate-specific antigen and biopsy.

OBJECTIVE: To describe local disease control after radical external beam radiotherapy of prostatic carcinoma, as judged by digital rectal examination (DRE), transrectal ultrasonography (TRUS)-guided biopsies and estimates of serum prostate-specific antigen (PSA). PATIENTS AND METHODS: The study comprised 175 patients (mean age 67.5 years, range 49-82; > 90% aged > or = 60 years) with localized prostatic carcinoma (T1-T3C, N0, M0) who underwent external beam radiation therapy (70 Gy), and were then regularly followed with a DRE, measurements of serum PSA and TRUS-guided biopsies to determine the outcome. RESULTS: The DRE revealed four patients with evidence of residual cancer in the prostate and biopsies showed no evidence of residual cancer in 131 (75%) of the patients. There was no correlation of residual cancer with tumour stage or grade but tumour size, as estimated by TRUS, correlated with the results of the biopsy. The nadir serum PSA level was < or = 1.0 ng/mL in 116 (66%) of the patients, of whom 76 (43%) had a nadir serum PSA level of < or = 0.5 ng/mL. The median time to the nadir level was 11 months. Serum PSA progression (> 4.0 ng/mL) at the latest PSA measurement after reaching the nadir occurred in 13% of the patients with a nadir PSA of < or = 0.5 ng/mL and in 25 of the 29 (86%) patients with a nadir serum PSA > 2.0 ng/mL. Cox regression analysis showed that tumour size and rectal irradiation dose were the most important factors for local control. CONCLUSIONS: Radiotherapy is effective in achieving local control in small prostate cancer tumours but less effective in large tumours. Tumour size and dorsal extension of the irradiated target, the rectal dose, were the two important factors for local control. A serum PSA level of < or = 1.0 ng/mL was associated with a higher chance of prolonged disease control.