High-dose Radiotherapy For Prostate Cancer Research Articles

High-dose radiotherapy and risk-adapted androgen deprivation in localised prostate cancer (DART 01/05): 10-year results of a phase 3 randomised, controlled trial

The optimal duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains controversial. The DART 01/05 trial was designed to determine whether long-term androgen deprivation is superior to short-term androgen deprivation when combined with high-dose radiotherapy. The 5-year results showed that 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy significantly improved biochemical control, metastasis, and overall survival, especially in patients with high-risk disease. In this report, we present the 10-year final results of the trial. This open-label, phase 3, randomised, controlled trial was done in ten hospitals in Spain. The eligibility criteria included patients aged 18 years or older with histologically confirmed T1c to T3, N0, and M0 adenocarcinoma of the prostate, according to the 2002 classification of the American Joint Committee on Cancer, with intermediate-risk and high-risk factors, prostate-specific antigen (PSA) less than 100 ng/mL, and a Karnofsky performance score of at least 70%. Patients were randomly assigned (1:1) to receive 4 months of neoadjuvant and concomitant short-term androgen deprivation (STAD) plus high-dose radiotherapy (minimum dose 76 Gy; median dose 78 Gy) or to receive the same treatment followed by 24 months of adjuvant long-term androgen deprivation (LTAD), via a randomisation scheduled generated by Statistical Analysis Software programme (version 9.1) and an interactive web response system. Patients assigned to the STAD group received 4 months of neoadjuvant and concomitant androgen deprivation (oral flutamide 750 mg per day or oral bicalutamide 50 mg per day) with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy was added during the first 2 months of treatment. Patients assigned to LTAD continued with goserelin every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival at 5 years. For this 10-year study we analysed overall survival, metastasis-free survival, biochemical disease-free survival, and cause-specific survival. Analysis was by intention to treat. This trial is closed and is registered at ClinicalTrials.gov (NCT02175212) and in the EU Clinical Trials Register (EudraCT 2005-000417-36). Between Nov 7, 2005, and Dec 20, 2010, 355 patients were enrolled. One patient in the STAD group withdrew from the trial, hence 354 participants were randomly assigned to STAD (n=177) or LTAD (n=177). The median follow-up was 119·4 months (IQR 100·6-124·3). The 10-year biochemical disease-free survival for LTAD was 70·2% (95% CI 63·1-77·3) and for STAD was 62·3% (54·9-69·7; hazard ratio [HR] 0·84; 95% CI 0·50-1·43; p=0·52). At 10 years, overall survival was 78·4% (72·1-84·8) for LTAD and 73·3% (66·6-80·0) for STAD (HR 0·84; 95% CI 0·55-1·27; p=0·40), and metastasis-free survival was 76·0% (69·4-82·7) for LTAD and 70·9% (64·0-77·8) for STAD (HR 0·90; 95% CI, 0·37-2·19; p=0·81). For the subgroup of high-risk patients, the 10-year biochemical disease-free survival was 67·2% (57·2-77·2) for LTAD and 53·7% (43·3-64·1) for STAD (HR 0·90; 95% CI 0·49-1·64; p=0·73), the 10-year overall survival was 78·5% (69·6-87·3) for LTAD and 67·0% (57·3-76·7) for STAD (HR 0·58; 95% CI 0·33-1·01; p=0·054), and the 10-year metastasis-free survival was 76·6% (95% CI 67·6-85·6) for LTAD and 65·0% (55·1-74·8) for STAD (HR 0·89; 95% CI 0·33-2·43; p=0·82). Only 11 (3%) of 354 patients died from prostate cancer, all of them in the high-risk subgroup (five in the LTAD group and six in the STAD group). 76 (21%) patients died from other causes (mainly second malignancies in 31 [9%] and cardiovascular disease in 21 [6%]). No treatment-related deaths were observed. After an extended 10-year follow-up, we were unable to support the significant benefit of LTAD reported at 5 years. However, the magnitude of the benefit was clinically relevant in high-risk patients. Intermediate-risk patients treated with high-dose radiotherapy do not benefit from LTAD. A biological characterisation with the inclusion of genomic testing is needed in the decision-making process. Grupo de Investigación en Oncología Radioterápica and Sociedad Española de Oncología Radioterápica, the National Health Investigation Fund, and AstraZeneca.

OC-0338 Prognostic value of testosterone following androgen deprivation and high-dose radiotherapy in prostate cancer

OC-0338 Prognostic value of testosterone following androgen deprivation and high-dose radiotherapy in prostate cancer

Surgery for rectal cancer after high-dose radiotherapy for prostate cancer: is sphincter preservation relevant?

The feasibility and outcome of sphincter-saving resection for rectal cancer were assessed in patients previously treated by high-dose radiotherapy for prostate cancer. Between 2000 and 2012, 1066 patients underwent rectal excision for rectal cancer. Of these, 236 were treated by conventional radiotherapy (45 Gy) and sphincter-saving resection (Group A) and 12 were treated by external-beam radiotherapy (EBRT) for prostate cancer (70 Gy) and sphincter-saving resection (Group B) of whom five had a metachronous and seven a synchronous cancer. The end-points were surgical morbidity, pelvic sepsis, reoperation and definitive stoma. Tumour characteristics were similar in both groups. Surgical morbidity (67% vs 25%, P = 0.004), anastomotic leakage (50% vs 10%, P = 0.001, and reoperation (50% vs 17%, P = 0.011) were significantly higher in Group B. Multivariate analyses showed that EBRT for prostate cancer was the only independent factor for anastomotic leakage (OR = 5.12; 95% CI 1.45-18.08; P = 0.011) and definitive stoma (OR = 10.56; 95% CI 3.02-39.92; P < 0.001). High-dose radiotherapy for prostate cancer increases morbidity from rectal surgery and the risk of a permanent stoma. This suggests that a delayed coloanal anastomosis or a Hartmann procedure should be proposed as an alternative to low anterior resection in this population.

High-dose radiotherapy with short-term or long-term androgen deprivation in localised prostate cancer (DART01/05 GICOR): a randomised, controlled, phase 3 trial

The optimum duration of androgen deprivation combined with high-dose radiotherapy in prostate cancer remains undefined. We aimed to determine whether long-term androgen deprivation was superior to short-term androgen deprivation when combined with high-dose radiotherapy. In this open-label, multicentre, phase 3 randomised controlled trial, patients were recruited from ten university hospitals throughout Spain. Eligible patients had clinical stage T1c-T3b N0M0 prostate adenocarcinoma with intermediate-risk and high-risk factors according to 2005 National Comprehensive Cancer Network criteria. Patients were randomly assigned (1:1) using a computer-generated randomisation schedule to receive either 4 months of androgen deprivation combined with three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range 76-82 Gy; short-term androgen deprivation group) or the same treatment followed by 24 months of adjuvant androgen deprivation (long-term androgen deprivation group), stratified by prostate cancer risk group (intermediate risk vs high risk) and participating centre. Patients assigned to the short-term androgen deprivation group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaneous goserelin (2 months before and 2 months combined with high-dose radiotherapy). Anti-androgen therapy (flutamide 750 mg per day or bicalutamide 50 mg per day) was added during the first 2 months of treatment. Patients assigned to long-term suppression continued with the same luteinising hormone-releasing hormone analogue every 3 months for another 24 months. The primary endpoint was biochemical disease-free survival. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02175212. Between Nov 7, 2005, and Dec 20, 2010, 178 patients were randomly assigned to receive short-term androgen deprivation and 177 to receive long-term androgen deprivation. After a median follow-up of 63 months (IQR 50-82), 5-year biochemical disease-free survival was significantly better among patients receiving long-term androgen deprivation than among those receiving short-term treatment (90% [95% CI 87-92] vs 81% [78-85]; hazard ratio [HR] 1·88 [95% CI 1·12-3·15]; p=0·01). 5-year overall survival (95% [95% CI 93-97] vs 86% [83-89]; HR 2·48 [95% CI 1·31-4·68]; p=0·009) and 5-year metastasis-free survival (94% [95% CI 92-96] vs 83% [80-86]; HR 2·31 [95% CI 1·23-3·85]; p=0·01) were also significantly better in the long-term androgen deprivation group than in the short-term androgen deprivation group. The effect of long-term androgen deprivation on biochemical disease-free survival, metastasis-free survival, and overall survival was more evident in patients with high-risk disease than in those with low-risk disease. Grade 3 late rectal toxicity was noted in three (2%) of 177 patients in the long-term androgen deprivation group and two (1%) of 178 in the short-term androgen deprivation group; grade 3-4 late urinary toxicity was noted in five (3%) patients in each group. No deaths related to treatment were reported. Compared with short-term androgen deprivation, 2 years of adjuvant androgen deprivation combined with high-dose radiotherapy improved biochemical control and overall survival in patients with prostate cancer, particularly those with high-risk disease, with no increase in late radiation toxicity. Longer follow-up is needed to determine whether men with intermediate-risk disease benefit from more than 4 months of androgen deprivation. Spanish National Health Investigation Fund, AstraZeneca.

Cardiac avoidance in breast radiotherapy: many choices for a worthwhile objective.

In this Research Topic, Goyal and Haffty have collected a series of papers on the emerging field of cardio-oncology. Indeed, Darby et al.’s paper demonstrating an incremental 7% increase in risk of ischemic events per gray increase in mean heart dose has been a watershed moment in our efforts to improve the therapeutic ratio of adjuvant breast radiotherapy (1). While a 0.07 increase over baseline risk per Sievert may seem high, it is important to understand this relative increase in risk in the context of the absolute baseline risk. Darby and colleagues do not provide a denominator for eligible patients in the two population registries from which they drew their cases and controls. Instead, they estimate the baseline risk using data from 15 Western European nations, and in Table S12 of the Supplementary Material, go on to estimate the absolute risk increase by age 80 years in women exposed to RT at various ages and with various co-morbid risk profiles. The excess absolute risks appear to be modest at first glance. For example, for a young 40-year-old woman receiving a high mean heart dose of 10 Gy, the estimated absolute excess risk of dying from cardiac disease is about 1.4%. Should the same woman have at least one co-morbid risk factor, her excess risk is 2.3%. These numbers may seem small, but are certainly relevant at the population level, especially given that the mortality benefit of adjuvant radiotherapy is also modest (2). Current efforts at reducing the risks of incidental cardiac irradiation have included advanced radiotherapy techniques for cardiac avoidance such as breath hold (3), gating treatments (4), proton therapy (5), prone positioning (6), and combinations thereof such as respiratory gating in the prone position (7). Cardiac avoidance techniques are illustrative of the general potential that technological innovations can have on human health. Going back to the very development of megavoltage machines, improvements in radiation delivery have consistently improved the therapeutic ratio in any number of settings. Recent reports have demonstrated fewer late second malignancies in children treated with proton therapy (8), lower rates of desquamation in breast cancer patients treated with IMRT (9), higher rates of local control in lung cancer patients treated with SBRT (10), and improved biochemical control in patients treated with highly conformal, high-dose radiotherapy for prostate cancer (11). Similar improvements in image-guided gynecological brachytherapy (12), IMRT in head/neck (13), GI (14), and gynecological malignancies (15), as well as intracranial SRS (16) have all demonstrated better outcomes compared with control data. Even as the calls for controlling costs become ever more constant, it is important to remember that the current excitement for a genomically driven model of cancer care has become possible only because of technological improvements in sequencing technologies. As such, continued funding, both federal and private, for technology innovations is critical and should not be relegated to lower tiers of priority. Coming back to breast cancer patients and the cardiac risks they face from radiotherapy, one additional (seemingly obvious) point needs to be made. While we can invoke continually advancing technologies for the purposes of cardiac avoidance (17), sometimes a return to simpler solutions may be all that is needed. Many women with early-stage breast cancer are eligible for off-protocol accelerated partial breast irradiation as a standard of care option (18). As one would expect, irradiating a smaller volume of breast tissue leads to lower incidental heart doses (19). Current studies and protocols examining, for example, breath hold parameters or prone positioning often include a large contingent of women who are candidates for partial breast irradiation. One rather elegant way to avoid treating the heart is to simply not treat it.

P091 Predictors of international prostate symptom scores (IPSS) worsening at the end of high-dose radiotherapy for prostate cancer: First results of a large prospective cohort study (DUE-01)

P091 Predictors of international prostate symptom scores (IPSS) worsening at the end of high-dose radiotherapy for prostate cancer: First results of a large prospective cohort study (DUE-01)

O8 Predicting late faecal incontinence after high-dose radiotherapy for prostate cancer: Development of a ready to use paper model based on artificial neural network analysis

O8 Predicting late faecal incontinence after high-dose radiotherapy for prostate cancer: Development of a ready to use paper model based on artificial neural network analysis

Stamp Test Delivers Message on Erectile Dysfunction After High-dose Intensity-modulated Radiotherapy for Prostate Cancer

To evaluate erectile function after high-dose radiotherapy for prostate cancer using the International Index of Erectile Function, Expanded Prostate Cancer Index Composite, and stamp test. Men with favorable and intermediate-risk prostate cancer were assigned to receive prostate intensity-modulated radiotherapy (IMRT) versus an erectile tissue-sparing IMRT technique in a Phase III randomized, prospective study. The stamp test and International Index of Erectile Function and Expanded Prostate Cancer Index Composite questionnaires were completed at baseline and 6 months, 1 year, and 2 years after IMRT. The Sexual Health Inventory for Men scores were abstracted from the International Index of Erectile Function questionnaire. A partner questionnaire, designated IIEF-P, modeled after the International Index of Erectile Function questionnaire but from the perspective of the partner, was also collected. The data from 94 men who were enrolled in the trial and who had completed ≥1 questionnaire or 1 stamp test were analyzed. The median age of the patient population was 62.5 years. The median radiation dose was 76 Gy (range 74-80). At 6 months and 1 year after high-dose IMRT, a positive stamp result correlated significantly with the median Expanded Prostate Cancer Index Composite sexual summary, sexual function, and bother subscale scores. Additionally, 6 months after IMRT, the stamp test correlated with the median International Index of Erectile Function, International Index of Erectile Function sexual function domain, and Sexual Health Inventory for Men scores. Robust concordance for the International Index of Erectile Function and Sexual Health Inventory for Men scores was appreciated between responding patient and partner pairs. Nocturnal tumescence, as indicated by a positive stamp test, correlated well with established quality of life questionnaires after IMRT. The stamp test should strongly be considered as an objective measure of erectile function in future studies of erectile dysfunction in patients with prostate cancer.

Increasing the risk of late rectal bleeding after high-dose radiotherapy for prostate cancer: The case of previous abdominal surgery. Results from a prospective trial

PurposeTo evaluate and discuss the role of specific types of abdominal surgery (SURG) before radical radiation therapy as a risk factor for late rectal toxicity in prostate cancer patients. MethodsResults concerning questionnaire-based scored late bleeding and faecal incontinence in 718 patients with a complete follow-up of 36months were analysed, focusing on the impact of specific pre-radiotherapy abdominal/pelvic surgery procedures. Patients were accrued in the prospective study AIROPROS 0102. Different types of surgery (rectum-sigma resection, kidney resection, cholecystectomy or appendectomy) were considered as covariates together with a number of different parameters previously found to be predictive of late toxicity and including clinical as well as dosimetric parameters. Univariate (UVA) and multivariate (MVA) logistic analyses were carried out. ResultsIn total 69/718 patients were previously submitted to one or more surgical procedures, mostly cholecystectomy (n=21) and appendectomy (n=27). Actuarial incidences of G2–G3 and G3 bleeding were 52 (7.2%) and 24 (3.3%) respectively; 19 (2.6%) chronic incontinence events were registered.Cholecystectomy was found to be highly correlated with late rectal bleeding at UVA: OR=4.3 and p=0.006 for G2–G3 and OR=5.4 and p=0.01 for G3. Considering MVA (including dosimetric and clinical factors), G2–G3 bleeding was significantly correlated to cholecystectomy (OR=6.5, p=0.002), V75Gy (OR=1.074, p=0.003) and secondarily with appendectomy (OR=2.7, p=0.10), presence of acute radioinduced rectal bleeding (OR=1.70, p=0.21) and androgen deprivation (OR=0.67, p=0.25).Appendectomy (OR=5.9, p=0.004) and cholecystectomy (OR=5.5, p=0.016) were very strong predictors of G3 bleeding with V75Gy playing a less significant role (OR=1.037, p=0.26). Conversely, no specific surgery was correlated with actuarial or chronic incontinence. ConclusionsThis analysis highlights previous SURG as the best predictor of late rectal bleeding. Among the different types of abdominal surgery, cholecystectomy and appendectomy play the major role, especially for severe late bleeding.

Improving Positioning in High-Dose Radiotherapy for Prostate Cancer: Safety and Visibility of Frequently Used Gold Fiducial Markers

The use of gold fiducial markers (GFMs) for prostate positioning in high-dose radiotherapy is gaining interest. The purpose of this study was to compare five GFMs regarding feasibility of ultrasound-based implantation in the prostate and intraprostatic lesion (IPL); toxicity; visibility on transabdominal ultrasound (TU) and cone-beam CT (CBCT); reliability of automatic, soft tissue, and GFM-based CBCT patient positioning by comparing manual and automatic fusion CBCT. Twenty-five patients were included. Pain and toxicity were scored after implantation and high-dose radiotherapy. Fisher exact test was used to evaluate the correlation of patients' characteristics and prostatitis. Positioning was evaluated on TU and kilovoltage CBCT images. CBCT fusion was performed automatically (Elekta XVI technology, release 3.5.1 b27, based on grey values) and manually on soft tissue and GFMs. Pearson correlation statistics and Bland-Altman evaluation were used. Five GFMs were compared. Twenty percent of the patients developed prostatitis despite antibiotic prophylaxis. Cigarette smoking was significantly correlated with prostatitis. The visualization of all GFMs on TU was disappointing. Consequently we cannot recommend the use of these GFMs for TU-based prostate positioning. For all GFMs, there was only fair to poor linear correlation between automatic and manual CBCT images, indicating that even when GFMs are used, an operator evaluation is imperative. However, when GFMs were analyzed individually, a moderate to very strong correlation between automatic and manual positioning was found for larger GFMs in all directions. The incidence of prostatitis in our series was high. Further research is imperative to define the ideal preparation protocol preimplantation and to select patients. Automatic fusion is more reliable with larger GFMs at the cost of more scatter. The stability of all GFMs was proven.

Toxicity after Intensity-Modulated, Image-Guided Radiotherapy for Prostate Cancer

:To evaluate toxicity after dose-escalated radiotherapy for prostate cancer using intensity-modulated treatment planning (IMRT) and image-guided treatment (IGRT) delivery. 100 patients were treated with simultaneous integrated boost (SIB) IMRT for prostate cancer: doses of 76.23 Gy and 60 Gy in 33 fractions were prescribed to the prostate and the seminal vesicles, respectively, for intermediate- and high-risk patients (n = 74). The total dose was 73.91 Gy in 32 fractions for low-risk patients and after transurethral resection of the prostate (n = 26). The pelvic lymphatics were treated with 46 Gy in 25 fractions in patients with high risk of lymph node metastases using an SIB to the prostate (n = 25). IGRT was practiced with cone-beam computed tomography. Acute and late gastrointestinal (GI) and genitourinary (GU) toxicity was evaluated prospectively (CTCAE v3.0). Treatment was completed as planned by all patients. Acute GI and GU toxicity grade ≥ 2 was observed in 12% and 42% of the patients, respectively, with 4% suffering from GU toxicity grade 3. 6 weeks after treatment, the incidence of acute toxicity grade ≥ 2 had decreased to 12%. With a median follow-up of 26 months, late GI and GU toxicity grade ≥ 2 was seen in 1.5% and 7.7% of the patients at 24 months. Four patients developed late toxicity grade 3 (GI n = 1; GU n = 3). Presence of acute GI and GU toxicity was significantly associated with late GI (p = 0.0007) and GU toxicity (p = 0.006). High-dose radiotherapy for prostate cancer using IMRT and IGRT resulted in low rates of acute toxicity and preliminary results of late toxicity are promising.

Does High-dose Radiotherapy for Prostate Cancer Harm the Hip Joints?

Recent studies have demonstrated an improved biochemical control with increasing radiation dose in selected patients with prostate cancer. Sophisticated radiation techniques are used to accomplish this goal, e.g., IMRT. However, constraints have to be respected in terms of radiation damage to the normal tissues, particularly with regard to the rectum and bladder. Although experimental protocols on dose escalation usually also limit the dose to the hip joints, scarce data exist on the impact of pelvic radiotherapy to the femoral head and acetabulum.

Is Hormone Therapy a Protective Factor for Late Hematuria After High-Dose Radiotherapy in Prostate Cancer?

To identify potential clinical and dosimetric factors predictive of a higher risk of grade 2 or higher late hematuria in patients with prostate cancer treated with high-dose radiotherapy. For this purpose, we have analyzed 229 T1c-T3b prostate cancer patients treated with 3-dimensional conformal radiotherapy (3DCRT) in a prospective dose escalation study and with a minimum follow-up of 1 year. The mean radiation dose was 79 Gy (range 72.1 to 84.14 Gy) and the mean follow-up was 47 months (range 14 to 95). One hundred eighteen patients also received androgen deprivation (AD) for high-risk disease. Univariate and multivariate analysis (MVA) were performed to identify variables significantly associated with late hematuria. Of the 31 (14%) patients with grade 2 or higher genitourinary toxicity, hematuria was the main symptom in 24 (10.5%) with only 1 patient (0.5%) experiencing grade 3 hematuria. On statistical analysis, all the dosimetric parameters failed to show a significant correlation with grade 2 or higher hematuria. On MVA, prior transurethral resection of the prostate (TURP) was significantly associated with a higher risk of late hematuria (relative risk [RR] = 2.8; P = 0.026), whereas long-term AD was correlated with a significantly decreased risk (RR = 0.21; P = 0.019). TURP was a relevant factor increasing 3 times the risk of late hematuria in prostate cancer patients treated with 3DCRT. Conversely, long-term AD resulted in a protective factor decreasing 5 times the risk of late hematuria. To our knowledge, this is the first study reporting a protecting effect of long-term hormones in late toxicity after radiotherapy.

Phase II Feasibility Study of High-Dose Radiotherapy for Prostate Cancer Using Proton Boost Therapy: First Clinical Trial of Proton Beam Therapy for Prostate Cancer in Japan

To assess the feasibility of high-dose radiotherapy for prostate cancer using proton boost therapy following photon radiotherapy. The primary endpoint was acute grade 3 or greater genitourinary (GU) and gastrointestinal (GI) toxicities. The study included patients with clinical stage T1-3N0M0 prostate cancer. Radiotherapy consisted of 50 Gy/25 fx photon irradiation to the prostate and the bilateral seminal vesicles followed by proton boost of 26 Gy(E)/13 fx to the prostate alone. Hormonal therapy was allowed before and during the radiation therapy. Between January 2001 and January 2003, 30 patients were enrolled in this study. Acute grade 1/2 GU and GI toxicities were observed in 20/4 and 17/0 patients, respectively. With the median follow-up period of 30 months (range 20-45), late grade 1/2 GU and GI toxicities occurred in 2/3 and 8/3 patients, respectively. No grade 3 or greater acute or late toxicities were observed. All patients were alive, but six patients relapsed biochemically after 7-24 months. Proton boost therapy following photon radiotherapy for prostate cancer is feasible. To evaluate the efficacy and safety of proton beam therapy, a multi-institutional phase II trial is in progress in Japan.

High-dose rate interstitial with external beam irradiation for localized prostate cancer – results of a prospective trial

Purpose: A prospective phase II trial was carried out to test the feasibility and effectiveness of a combined interstitial with external beam radiotherapy approach for localized prostate cancer. Materials and methods: Between October 1992 and December 1994, 82 evaluable patients were treated. T2 and T3 tumours, according to the AJCC classification system of 1992, were found in 21 and 61 cases, respectively. The median follow-up was 24 months; three patients were lost during follow-up. All of the patients were pathologically proven to be node-negative by laparoscopic node dissection of the fossa obturatoria region. A dose of 9 Gy a week was prescribed during the first and second weeks of treatment (10 Gy each week from October 1992 to December 1993) interstitially with high-dose rate Iridium-192 brachytherapy to the prostate and tumour extension beyond the capsule. External beam four-field box irradiation was then given to the prostate to a dose of 45 Gy/25 fractions (40 Gy/20 fractions from October 1992 to December 1993). Results: Before starting treatment, a PSA value of ≥10 ng/ml was found in 64.6% (53/82) of patients with a median PSA of 14.0 ng/ml. The median PSA 3, 12 and 24 months after completion of therapy was 1.20, 0.78 and 0.70 ng/ml, respectively. The PSA value was <1.0 ng/ml in 52.9% of patients at 2 years. Negative punch biopsies 12 and 24 months after therapy were observed in 69.8% (44/63) and 73.1% (38/52) of patients, respectively. A positive biopsy combined with a PSA value of >1.0 ng/ml was considered as local failure. The local tumour control rate was 79.5% at 2 years. Acute side-effects were not increased relative to external beam irradiation alone. Severe side-effects were observed in three patients (two of the three patients had additional risk factors (colitis ulcerosa and diabetes mellitus)); they developed rectourethral fistulae requiring colostomy after biopsies from the anterior rectal wall. Conclusion: The described method is feasible and well tolerable. The three complications observed were not caused by irradiation alone. Biopsies from the anterior rectal wall after definitive high-dose radiotherapy for prostate cancer have to be seen as obsolete. The rate of negative prostate biopsies of 73.1% after 24 months represents an encouraging result.