Per Fransson

Endocrine treatment, with or without radiotherapy, in locally advanced prostate cancer (SPCG-7/SFUO-3): an open randomised phase III trial.

BACKGROUND Several studies have shown the efficacy of endocrine therapy in combination with radiotherapy in high-risk prostate cancer. To assess the effect of radiotherapy, we did an open phase III study comparing endocrine therapy with and without local radiotherapy, followed by castration on progression. METHODS This randomised trial included men from 47 centres in Norway, Sweden, and Denmark. Between February, 1996, and December, 2002, 875 patients with locally advanced prostate cancer (T3; 78%; PSA<70; N0; M0) were centrally randomly assigned by computer to endocrine treatment alone (3 months of total androgen blockade followed by continuous endocrine treatment using flutamide; 439 patients), or to the same endocrine treatment combined with radiotherapy (436 patients). The primary endpoint was prostate-cancer-specific survival, and analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787. FINDINGS After a median follow-up of 7.6 years, 79 men in the endocrine alone group and 37 men in the endocrine plus radiotherapy group had died of prostate cancer. The cumulative incidence at 10 years for prostate-cancer-specific mortality was 23.9% in the endocrine alone group and 11.9% in the endocrine plus radiotherapy group (difference 12.0%, 95% CI 4.9-19.1%), for a relative risk of 0.44 (0.30-0.66). At 10 years, the cumulative incidence for overall mortality was 39.4% in the endocrine alone group and 29.6% in the endocrine plus radiotherapy group (difference 9.8%, 0.8-18.8%), for a relative risk of 0.68 (0.52-0.89). Cumulative incidence at 10 years for PSA recurrence was substantially higher in men in the endocrine-alone group (74.7%vs 25.9%, p<0.0001; HR 0.16; 0.12-0.20). After 5 years, urinary, rectal, and sexual problems were slightly more frequent in the endocrine plus radiotherapy group. INTERPRETATION In patients with locally advanced or high-risk local prostate cancer, addition of local radiotherapy to endocrine treatment halved the 10-year prostate-cancer-specific mortality, and substantially decreased overall mortality with fully acceptable risk of side-effects compared with endocrine treatment alone. In the light of these data, endocrine treatment plus radiotherapy should be the new standard.

Self‐assessment questionnaire for evaluating urinary and intestinal late side effects after pelvic radiotherapy in patients with prostate cancer compared with an age‐matched control population

Background. Pelvic irradiation to patients with prostate cancer is accompanied by urinary and intestinal reactions. In men older than 60 years, treatment‐induced problems should be evaluated in relation to problems in an age‐matched nonirradiated population.

Cohort Profile: The National Prostate Cancer Register of Sweden and Prostate Cancer data Base Sweden 2.0

In 1987, the first Regional Prostate Cancer Register was set up in the South-East health-care region of Sweden. Other health-care regions joined and since 1998 virtually all prostate cancer (PCa) cases are registered in the National Prostate Cancer Register (NPCR) of Sweden to provide data for quality assurance, bench marking and clinical research. NPCR includes data on tumour stage, Gleason score, serum level of prostate-specific antigen (PSA) and primary treatment. In 2008, the NPCR was linked to a number of other population-based registers by use of the personal identity number. This database named Prostate Cancer data Base Sweden (PCBaSe) has now been extended with more cases, longer follow-up and a selection of two control series of men free of PCa at the time of sampling, as well as information on brothers of men diagnosed with PCa, resulting in PCBaSe 2.0. This extension allows for studies with case-control, cohort or longitudinal case-only design on aetiological factors, pharmaceutical prescriptions and assessment of long-term outcomes. The NPCR covers >96% of all incident PCa cases registered by the Swedish Cancer Register, which has an underreporting of <3.7%. The NPCR is used to assess trends in incidence, treatment and outcome of men with PCa. Since the national registers linked to PCBaSe are complete, studies from PCBaSe 2.0 are truly population based.

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

Treatment of localized prostate carcinoma (LPC) using radiotherapy (RT) can induce disturbances in a patients 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).

Quality of life in patients with locally advanced prostate cancer given endocrine treatment with or without radiotherapy: 4-year follow-up of SPCG-7/SFUO-3, an open-label, randomised, phase III trial

BACKGROUND Androgen treatment for prostate cancer can adversely affect functional domains of quality of life. We aimed to assess quality of life in men with locally advanced prostate cancer in an open-label phase III randomised comparison between lifelong endocrine treatment with and without radiotherapy. METHODS We obtained quality-of-life information from 872 (99%) of 875 eligible men with locally advanced prostate cancer (T3; 78%) who were randomly assigned, between 1996 and 2002, to 3 months of total androgen blockade followed by continuous endocrine treatment (439 patients) or the same hormonal treatment with radiotherapy 3 months after randomisation (436 patients). Prospective outcomes included patient-reported symptoms and quality of life assessed with questionnaires from baseline to 4 years after randomisation. Analysis was by intention to treat. This study is registered as an international standard randomised controlled trial, number ISRCTN01534787. FINDINGS 438 of 439 men assigned endocrine treatment and 434 of 436 assigned endocrine plus radiotherapy completed at least one questionnaire. Missing data at baseline and during follow-up was equally distributed between groups. At 4 years, 64 (18%) of 353 patients on combined therapy and 39 (12%) of 337 on endocrine-alone therapy had moderate to severe urinary bother (p=0.005), and 16 (4%) of 355 on combined therapy and five (2%) of 338 on endocrine treatment alone had pain while urinating (p=0.024). 37 (11%) of 350 in the combined group and 23 (7%) of 35 in the endocrine-only group had overall bother from all bowel symptoms (p=0.022). 281 (85%) of 332 in the combined-treatment group and 227 (72%) of 313 in the endocrine-only group had erectile dysfunction (p=0.0002). Quality of life at 4 years was similar, with the exception of decreased social function in patients receiving endocrine treatment plus radiotherapy. INTERPRETATION Although addition of radiotherapy to endocrine treatment significantly increased some treatment-related symptoms, none were serious. Given the substantial survival benefit of combined treatment, the increase of symptoms seems acceptable and has little extra effect on quality of life after 4 years compared with endocrine treatment alone.

Self-assessed sexual function after pelvic irradiation for prostate carcinoma : Comparison with an age-matched control group

Treatment of localized prostate carcinoma is often accompanied by disturbances in sexual function. The patients own opinion and experience with these problems can be of great importance for his quality of life. In men older than 50 years, disturbances in sexual function are common. Treatment such as radiotherapy (RT), which can induce sexual dysfunction, should be evaluated in relation to the problems in an age‐matched population without prostate carcinoma.

Reliability and responsiveness of a prostate cancer questionnaire for radiotherapy-induced side effects

Abstract Few self-assessment cancer-specific questionnaires / modules have yet been developed for radiotherapy-induced side effects. The aim of the present study was to test the reliability and responsiveness of a prostate cancer (PC)-specific questionnaire. Thirty-one patients with PC graded their urinary and intestinal symptoms and their sexual function on the questionnaire. A doctor and a nurse performed a structured interview and graded the patients symptoms with the same questions. The procedure was performed at both the start and the end of the treatment. A high concordance regarding symptom detection was seen between the patient, nurse and the doctor. The inter-rater test shows intraclass correlation coefficient (ICC) values above 0.60 in all scales. The internal reliability exceeded the lower limit (Cronbach α >0.70) for all scales. The test–retest gave acceptable reliability for all scales (ICC ≥0.60). All scales indicated increased problems during radiotherapy. The questionnaire was proven to be valid for the evaluations of urinary and intestinal problems and for sexual function in PC patients.

Prospective evaluation of urinary and intestinal side effects after BeamCath® stereotactic dose-escalated radiotherapy of prostate cancer

BACKGROUND New data suggest that a higher radiation dose will improve outcome in treatment of localized prostate cancer. External beam radiotherapy (EBRT) may on the other hand induce disturbances in the patients urinary and intestinal function. Since 1997, 195 patients have been treated with a stereotactic boost of 4-8 Gy added to conventional 70 Gy EBRT. Late side effects were prospectively evaluated 3 years after dose-escalated EBRT. METHODS Urinary and intestinal problems were prospectively evaluated with a validated self-assessment questionnaire, the Prostate Cancer Symptom Scale (PCSS). Two hundred and eighty-seven patients completed the questionnaire at the 1 year follow-up, and 153 at 3 years after treatment. Pre-treatment mean age was 66 years. One hundred and sixty-eight patients were treated with the conformal technique and 195 were treated with the dose-escalated stereotactic BeamCath technique. Mean total dose in the conformal group (< or =70 Gy) was 66 Gy (60.8-70.4 Gy). The dose-escalated group consists of three dose levels, 74 Gy (n = 68), 76 Gy (n = 74), and 78 Gy (n = 53). RESULTS Analyzing the whole population 3 years after treatment, urgency and starting problems decreased in comparison to pre-treatment. A minor increase in urinary incontinence was reported 3 years after treatment in comparison to pre-treatment. No increases in other urinary symptoms were reported. Intestinal symptoms were slightly increased during the follow-up period in comparison to pre-treatment. Dose escalation with stereotactic EBRT (74-78 Gy) did not increase gastrointestinal or genitourinary late side effects at 1 year or 3 years in comparison to doses < or =70 Gy. CONCLUSIONS The stereotactic BeamCath EBRT technique facilitates safe dose escalation of patients with prostate cancer.

Population‐based study of long‐term functional outcomes after prostate cancer treatment

To evaluate long‐term urinary, sexual and bowel functional outcomes after prostate cancer treatment at a median (interquartile range) follow‐up of 12 (11–13) years.

Patient-reported lower urinary tract symptoms, urinary incontinence, and quality of life after external beam radiotherapy for localized prostate cancer – 15 years’ follow-up. A comparison with age-matched controls

Background. To prospectively examine the urinary toxicity and quality of life (QOL) in patients 15 years after external beam radiotherapy (EBRT) for localized prostate cancer (LPC) and compare the outcomes with results for age-matched controls. Material and methods. Urinary symptoms were assessed using the symptom-specific Prostate Cancer Symptom Scale (PCSS) questionnaire, and QOL was assessed with the European Organization for Research and Treatment of Cancer (EORTC)s Quality of Life Questionnaire (QLQ-C30). Both questionnaires were sent to the surviving 41 patients (25%) and the PCSS questionnaire was sent to 69 age-matched controls for comparison. Results. The response rate was 71% in the patient group and 59% in the control group. Two patients and four controls were excluded due to other cancer diagnoses, resulting in a total of 27 patients and 37 controls for inclusion in the analyses. The mean age in both groups was 78 years. In the patient group, incontinence had increased between the 8-year (mean=0.6) and the 15-year follow-up (mean=2.1; p=0.038). No other differences in urinary problems were seen between these two follow-ups. Increased incontinence, stress incontinence, and pain while urinating were reported by the patients in comparison with the controls at 15 years. Role function was worse in the patient group (mean=67.3) compared with the controls (mean=82.4; p=0.046). The patients also reported more appetite loss, diarrhea, nausea/vomiting, and pain than the controls. Conclusion. EBRT for LPC has divergent effects on urinary symptoms and QOL in comparison with age-matched controls. In our patient population, urinary incontinence increased between 8 and 15 years of follow-up. Otherwise, no differences in urinary symptoms were seen between 4 and 15 years. Incontinence, stress incontinence, and pain while urinating were increased after EBRT in comparison with the controls. Conventional EBRT did not result in a major deterioration in QOL 15 years after treatment.