The risk of second malignancies following prostate cancer radiotherapy in the era of conformal radiotherapy: a statement of the Prostate Cancer Working Group of the German Society of Radiation Oncology (DEGRO).

A significant number of prostate cancer patients are long-term survivors after primary definitive therapy, and the occurrence of late side effects, such as second primary cancers, has gained interest. The aim of this editorial is to discuss the most current evidence on second primary cancers based on six retrospective studies published in 2021-2024 using large data repositories not accounting for all possible confounding factors, such as smoking or pre-existing comorbidities. Overall, prostate cancer patients treated with curative radiotherapy have an increased risk (0.7-1%) of the development of second primary cancers compared to patients treated with surgery up to 25 years after treatment. However, current evidence suggests that the implementation of intensity modulated radiation therapy is not increasing the risk of second primary cancers compared to conformal 3D-planned radiotherapy. Furthermore, increasing evidence indicates that highly conformal radiotherapy techniques may not increase the probability of second primary cancers compared to radical prostatectomy. Consequently, future studies should consider the radiotherapy technique and other confounding factors to provide a more accurate estimation of the occurrence of second primary cancers.

Prostate cancer and elective nodal radiation therapy for cN0 and pN0-a never ending story? : Recommendations from the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO).

For prostate cancer, the role of elective nodal irradiation (ENI) for cN0 or pN0 patients has been under discussion for years. Considering the recent publications of randomized controlled trials, the prostate cancer expert panel of the German Society of Radiation Oncology (DEGRO) aimed to discuss and summarize the current literature. Modern trials have been recently published for both treatment-naïve patients (POP-RT trial) and patients after surgery (SPPORT trial). Although there are more reliable data to date, we identified several limitations currently complicating the definitions of general recommendations. For patients with cN0 (conventional or PSMA-PET staging) undergoing definitive radiotherapy, only men with high-risk factors for nodal involvement (e.g., cT3a, GS ≥ 8, PSA ≥ 20 ng/ml) seem to benefit from ENI. For biochemical relapse in the postoperative situation (pN0) and no PSMA imaging, ENI may be added to patients with risk factors according to the SPPORT trial (e.g., GS ≥ 8; PSA > 0.7 ng/ml). If PSMA-PET/CT is negative, ENI may be offered for selected men with high-risk factors as an individual treatment approach.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

[Treatment of primary oligometastatic prostate cancer]. / Die Therapie des primär oligometastasierten Prostatakarzinoms.

BACKGROUND: Multimodal treatment concepts are gaining in importance in the treatment of prostate cancer patients with primary oligometastatic disease. Data from randomized studies show that survival advantages can be achieved in this patient collective by the combination of local and systemic treatment compared to systemic treatment alone. OBJECTIVE: To analyze the available data on therapeutic approaches for oligometastatic prostate cancer. MATERIAL AND METHODS: Summary and discussion of current studies on systemic and local treatment of de novo oligometastatic prostate cancer. RESULTS: Systemic treatment continues to be the standard of care in the oligometastatic stage of prostate cancer. Furthermore, irradiation of the prostate is recommended for patients with a low metastasis burden after this led to an extension of the overall survival in a randomized phase III study. Large case series suggest that radical prostatectomy can also improve oncological endpoints. The results of prospective phase II studies on metachronous metastatic disease provide evidence that local ablative radiotherapy of individual metastases can improve progression-free survival; however, the value of this approach in de novo metastatic disease is just as unclear as that of a triple treatment combination consisting of local and extended systemic treatment. CONCLUSION: In addition to systemic treatment, irradiation of the prostate is a new standard of care for the oligometastatic stage ("low tumour burden").

[Treatment concepts for primary oligometastatic prostate cancer]. / Therapiekonzepte beim primär oligometastasierten Prostatakarzinom.

BACKGROUND: About 5% of prostate cancer patients have distant metastases at diagnosis. In these metastatic hormone-sensitive prostate cancers (mHSPC), systemic therapy is recommended, according to the guidelines. Moreover, metastasis-directed therapy (MDT) is discussed to prolong survival. OBJECTIVES: The contemporary literature concerning local therapy and MDT in patients with mHSPC is summarized. METHODS: Selective literature search. RESULTS: In 2018, randomized controlled data on local therapy in mHSPC patients were published by the authors of the STAMPEDE study. Here, patients were randomized between standard of care (SOC) ± radiotherapy to the prostate (RT). Within the overall cohort, no difference regarding 3­year overall survival (OS) was observed. Within a prespecified subgroup of patients with low metastatic burden. Similar results were observed in numerous retrospective studies analyzing radical prostatectomy; prospective randomized studies are pending. For MDT, there are no sufficient data in mHSPC patients yet. CONCLUSIONS: In the current guidelines, systematic therapy is standard of care in mHSPC patients. In patients with low metastatic burden, a survival benefit was observed when adding percutaneous RT to the prostate. Retrospective studies also suggest a benefit when adding RP. However, whether MDT prolongs survival is still unknown.

[Studies on radiotherapy of head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. / Strahlentherapeutische Studien bei Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: Radiotherapy is an important treatment option in patients with head and neck. At this year's annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, results of several studies on radiotherapy in patients with head and neck cancer were presented. MATERIALS AND METHODS: All abstracts and presentations from this year's ASCO Annual Meeting on radiotherapy in patients with head and neck cancer were screened and the most interesting results selected for further review. RESULTS: The ORATOR trial compared primary surgery in patients with oropharyngeal carcinoma (OPSCC) with primary radiochemotherapy (RCT), particularly in terms of swallowing, for which superiority of RCT was demonstrated. Furthermore, results were presented on the question of optimal cisplatin dosage in patients receiving adjuvant RCT. Higher cisplatin doses showed better outcome. In patients with nasopharyngeal carcinoma (NPC), neoadjuvant chemotherapy before RCT is a comparable alternative to RCT followed by adjuvant chemotherapy. In addition, results of studies were presented that examined the tolerability of combining immunotherapy with radiotherapy in the first-line setting. CONCLUSION: The data presented show promising approaches for the further development of radiotherapy, particularly in terms of combined RCT as well as the optimal sequencing and dosing of systemic therapies.

[Radiotherapeutic studies of head and neck cancer-highlights of the 2018 ASCO Annual Meeting]. / Strahlentherapeutische Studien bei Kopf-Hals-Tumoren ­ Highlights der ASCO-Jahrestagung 2018.

BACKGROUND: Radiotherapy is an important treatment option in patients with advanced head and neck cancer. At the 2018 Annual Meeting of the American Society of Clinical Oncology (ASCO), study results were presented that could further develop and modify existing therapy concepts in the future. MATERIALS AND METHODS: All ASCO abstracts and presentations concerning radiotherapy of head and neck cancer were screened and the most interesting abstracts were selected for further review. RESULTS: One major topic was the combination of radiation with immunotherapy. Presented trials included combination treatment of epidermal growth factor receptor (EGFR) antibodies and platin-based chemoradiotherapy, as well as programmed cell death protein 1 (PD-1) antibodies in combination with platin-based chemoradiotherapy or cetuximab radiotherapy. In one study, the impact of adjuvant (chemo)radiotherapy for overall survival of human papillomavirus (HPV)-associated head and neck cancer with low to intermediate risk was analyzed. Additionally, studies focusing on the prophylaxis or reduction of radiation-mediated oral mucositis were presented. CONCLUSION: The data presented do not justify a change of current treatment paradigms just yet. However, interesting developments can be expected in the coming years, particularly in the field of immunotherapy.

[When should the primary tumor of metastatic bladder or prostate cancer be treated using a nonsurgical regimen?] / Wann ist der Primärtumor eines Harnblasen- bzw. Prostatakarzinoms in der metastasierten Situation durch eine nicht-operative Maßnahme zu therapieren?

BACKGROUND: Patients with metastatic and locally advanced bladder or prostate cancer may suffer from pelvic symptoms such as pain, obstruction, and hemorrhage. Local tumor growth is associated with significant morbidity and systemic therapy is often ineffective. Local therapies such as bladder irrigation, transurethral resection of the prostate, and fulguration of bleeding vessels provide relief but often require repeated treatments. OBJECTIVES: The aim of this work was to review the current status of palliative pelvic radiotherapy for metastatic bladder and prostate cancer. MATERIALS AND METHODS: The available literature was evaluated and treatment recommendations are proposed depending on different clinical scenarios. RESULTS: To date, no standard regimen exists for the delivery of palliative pelvic radiotherapy. Various radiotherapy schedules manage successful and long-term palliation of pelvic symptoms in most patients and result in acceptable toxicity. For bladder cancer, the most common dose and fractionation regimens range from 20 Gy in 5 fractions to 40 Gy in 20 fractions. Some retrospective studies evaluated 6 weekly fractions of 6 Gy to a total dose of 36 Gy. For prostate cancer, the most common dose and fractionation regimes range from 30 Gy in 10 fractions to 50 Gy in 25 fractions. The symptomatic response rate is between 70 and 95%. CONCLUSIONS: Pelvic radiotherapy for patients with metastatic and locally advanced bladder or prostate cancer provides effective and long-term palliation of a variety of symptoms such as pain, obstruction, and hemorrhage, with acceptable toxicity. Future studies should investigate the optimal target dose and fractionation schedule.

Response Evaluation in Head and Neck Oncology: Definition and Prediction.

Curative treatment of head and neck squamous cell carcinoma includes surgery and/or (chemo)radiation, whereas in the palliative setting, chemotherapy and/or immunotherapy represent(s) the standard approach. With regard to quality control, methods for determining treatment response are sorely needed. For surgical therapy, histopathology is the standard quality control. Established criteria for high-risk patients include resection margins of the primary tumor and extracapsular extension of lymph node metastases. After definitive chemoradiation, treatment response is generally evaluated by tomographic imaging combined with endoscopy including re-biopsy of the tumor region. Single-cycle induction chemotherapy may be used to determine the radiosensitivity of tumors, helping to define surgical and nonsurgical treatment options. Innovative approaches with implications for prognosis include the analysis of immune infiltrates, liquid biopsy, molecular characterization (proteomics, genomics), molecular and functional imaging (PET-CT, PET-MRI), as well as advanced imaging data analysis (radio[geno]mics/texture analysis). Human papilloma virus, as a prognostically relevant parameter, is currently being investigated for de-escalation strategies. With regard to the extended personalization of oncologic therapy, markers predicting treatment response are desirable and seem to be important, also from a socioeconomic perspective.

[Radiotherapy in node-positive prostate cancer]. / Strahlentherapie beim nodal-positiven Prostatakarzinom.

BACKGROUND: There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. OBJECTIVES: This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. RESULTS: The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. CONCLUSION: There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

[Adjuvant vs. salvage radiotherapy after radical prostatectomy]. / Adjuvante vs. Salvage-Strahlentherapie nach radikaler Prostatektomie.

BACKGROUND: After radical prostatectomy (RP) the pre-RP PSA value, Gleason Score, pT-stage, state of seminal vesicles and state of surgical margins are key indicators for the risk of biochemical or clinical recurrence. Depending on the tumour stage, 50-70% of the high-risk patients suffer biochemical progression. The treatment options in these circumstances are adjuvant radiotherapy (ART, for an undetectable PSA) or salvage radiotherapy (SRT, for persisting PSA or PSA re-rising above detection limits). Data from ongoing randomised trials that compare ART and SRT directly have not yet been published. METHOD: A search in PubMed for ART and SRT after RP for prostate cancer was undertaken to compare the results of the 2 treatment approaches. RESULTS: 3 randomised phase-III studies have shown a nearly 20% advantage in terms of biochemical progression after ART (60-64 Gy) compared with a wait-and-see strategy. The largest effect was seen in patients with pT3 prostate cancer with positive surgical margins. According to the German S3-guidelines, SRT with at least 66 Gy can be offered to patients with a post-RP persisting PSA or a PSA re-rising above detection limits. 30-70% of these patients re-achieve an undetectable PSA. Thus, there is a second option for curative treatment. Due to the lower total dose, ART seems to be connected with fewer late complications than SRT. SRT, on the other hand, reduces the risk of potential interactions with post-RP complications and of overtreatment. There is a controversial discussion about the inclusion of the pelvic lymph nodes in the treatment volume, the additional application of anti-androgens and the total dose of both ART and SRT. CONCLUSIONS: The comparison of SRT after PSA progression with ART at a PSA below the detection limits cannot yet be judged conclusively. The indication for ART depends on the associated risk factors. However, regarding freedom from biochemical progression, it is backed up by high level evidence. If SRT is applied for biochemical progression, then it should be initiated early, i. e., at the lowest PSA possible.

The impact of adjuvant radiotherapy on the survival of primary breast cancer patients: a retrospective multicenter cohort study of 8935 subjects.

BACKGROUND: Radiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients: 1. Does guideline-adherent RT improve primary breast cancer patient survival? 2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters? 3. Does adjuvant RT compensate for an incomplete tumor resection (R1)? PATIENTS AND METHODS: In this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines. RESULTS: The patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613]. CONCLUSION: Our study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.

[The importance of pathology in the German prostate cancer study PREFERE]. / Die Bedeutung der Pathologie in der deutschen Prostatakrebsstudie PREFERE.

Prostate cancer is the most common carcinoma of elderly males and holds the third place in the ranking of cancer-specific mortality. However, total mortality rate of 3 % is low and half of the patients die from other diseases, which is for the most part due to significantly improved diagnostic methods and the increasing use of prostate-specific antigen (PSA) screening. This has led to a stage migration towards early tumor stages that are prognostically heterogeneous and require differentiated treatment. The German and European guidelines recommend four therapy options (i.e. radical prostatectomy, percutaneous irradiation, permanent seed implantation and active surveillance) for localized prostate cancer and from contemporary study data it is unclear which therapy is most beneficial. This will be the subject of the PREFERE trial, a prospective randomized multicentre trial which plans to recruit 7,600 patients and to observe them over a period of up to 17 years. The histopathological diagnosis of the primary biopsy plays a crucial role in the inclusion criteria, as this article outlines in detail.

Feasibility of 6-month maintenance cetuximab after adjuvant concurrent chemoradiation plus cetuximab in squamous cell carcinoma of the head and neck.

BACKGROUND: Close resection margins < 5 mm (CM) or extra capsular extent at the lymph nodes (ECE) impair the prognosis of patients with squamous cell cancer of the head and neck (SCCHN) scheduled for adjuvant radiochemotherapy. We conducted a multicenter phase II study to investigate toxicity and efficacy of additional cetuximab administered concomitantly and as maintenance for the duration of 6 months following adjuvant radiochemotherapy., Ppreliminary results on feasibility and acute toxicity on skin and mucosa are presented in this article. METHODS: Patients with SCCHN following CM resection or with ECE were eligible for the study. In all, 61.6 Gy (1.8/2.0/2.2 Gy, days 1-36) were administered using an integrated boost intensity-modulated radiotherapy (IMRT) technique. Cisplatin (20 mg/m(2), days 1-5 and days 29-33) and 5-fluorouracil (5-FU) as continuous infusion (600 mg/m(2), days 1-5 + days 29-33) were given concurrently. Cetuximab was started 7 days prior to radiochemotherapy at 400 mg/m(2) followed by weekly doses of 250 mg/m(2). Maintenance cetuximab began after radiochemotherapy at 500 mg/m(2) every 2 weeks for 6 months. RESULTS: Of the 55 patients (46 male, 9 female, mean age 55.6, range 29-70 years) who finished radiochemotherapy, 50 were evaluable for acute toxicity concerning grade III/IV toxicities of skin and mucosa. Grade 3-4 (CTC 3.0) mucositis, radiation dermatitis, and skin reactions outside the radiation portals were documented for 46, 28, and 14 % of patients, respectively. One toxic death occurred (peritonitis at day 57). Cetuximab was terminated in 5 patients due to allergic reactions after the first application. In addition, 22 % of patients discontinued cetuximab within the last 2 weeks or at the end of radiochemotherapy. Of patients embarking on maintenance treatment, 80 % were still on cetuximab at 3 months and 63 % at 5 months. Concurrent and maintenance treatment with cetuximab could be administered as scheduled in 48 % of patients. CONCLUSION: Adjuvant radiochemotherapy with concomitant and maintenance cetuximab is feasible and acute toxicities are within the expected range. Compliance within the first 3-5 months is moderate.

[PREFERE - the German prostatic cancer study: questions and claims surrounding study initiation in January 2013]. / PREFERE - die Deutsche Prostatakrebsstudie : Fragen und Behauptungen rund um den Studienbeginn im Januar 2013.

The PREFERE study is a multicenter randomized study of patients with low or early intermediate risk for prostatic cancer. The four treatment options, radical prostatectomy, percutaneous irradiation therapy, permanent seed implantation and active surveillance recommended by the German S3 guidelines and international guidelines will be tested and compared with respect to effectiveness and potential side effects. Over a period of 4 years a total of 7,600 patients are to be recruited and assigned to 1 of these 4 therapy forms according to personal preference (by possible exclusion of 1 or 2 therapy options) in a 2-4 arm study design by randomization.

Prostate cancer: ESMO Consensus Conference Guidelines 2012.

The first ESMO Consensus Conference on prostate cancer was held in Zurich, Switzerland, on 17-19 November 2011, with the participation of a multidisciplinary panel of leading professionals including experts in methodological aspects. Before the conference, the expert panel prepared clinically relevant questions about prostate cancer in four areas for discussion as follows: diagnosis and staging, management of early localized disease, management of advanced localized disease and systemic disease. All relevant scientific literature, as identified by the experts, was reviewed in advance. During the Consensus Conference, the panel developed recommendations for each specific question. The recommendations detailed here are based on an expert consensus after careful review of published data. All participants have approved this final update.

Neoadjuvant androgen deprivation therapy for prostate volume reduction, lower urinary tract symptom relief and quality of life improvement in men with intermediate- to high-risk prostate cancer: a randomised non-inferiority trial of degarelix versus goserelin plus bicalutamide.

AIMS: The treatment of intermediate- to high-risk prostate cancer with radical radiotherapy is usually in combination with neoadjuvant androgen deprivation therapy. The aim of the present trial was to investigate whether degarelix achieves comparable efficacy with that of goserelin plus bicalutamide as neoadjuvant therapy before radiotherapy. MATERIALS AND METHODS: The study was a randomised, parallel-arm, active-controlled, open-label trial in 244 men with a UICC prostate cancer TNM category T2b-T4, N0, M0, Gleason score ≥7, or prostate-specific antigen ≥10 ng/ml and a total prostate volume >30 ml, who were scheduled to undergo radical radiotherapy and in whom neoadjuvant androgen deprivation therapy was indicated. Eligible patients received treatment with either monthly degarelix (240/80 mg) or goserelin (3.6 mg) for 12 weeks, the latter patients also receiving bicalutamide (50 mg) for 17 days initially. The primary efficacy measure was the mean percentage reduction in total prostate volume from baseline at week 12 measured by transrectal ultrasound. The severity and relief of lower urinary tract symptoms were assessed by the International Prostate Symptom Score questionnaire. Quality of life was assessed by the eighth question of the International Prostate Symptom Score. About 50% of the patients had moderate to severe lower urinary tract symptoms at baseline. RESULTS: The total prostate volume decreased significantly from baseline to week 12 in both treatment groups, reaching -36.0 ± 14.5% in degarelix-treated patients and -35.3 ± 16.7% in goserelin-treated patients (adjusted difference: -0.3%; 95% confidence interval: -4.74; 4.14%). At the end of the therapy, more degarelix- than goserelin-treated patients reported International Prostate Symptom Score decreases of ≥3 points (37% versus 27%, P = 0.21). In addition, in patients with a baseline International Prostate Symptom Score of ≥13, the magnitude of the decrease was larger in degarelix- (n = 53) versus goserelin-treated patients (n = 17) (6.04 versus 3.41, P = 0.06). CONCLUSIONS: The efficacy of degarelix in terms of prostate shrinkage is non-inferior to that of goserelin plus bicalutamide. The added benefits of degarelix in terms of more pronounced lower urinary tract symptom relief in symptomatic patients could be the reflection of differences in the direct effects on extra-pituitary receptors in the lower urinary tract [Clinicaltrials.gov ID: NCT00833248].