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Context While urinary incontinence (UI) commonly occurs after radical prostatectomy (RP), it is unclear what factors increase the risk of UI development. Objective To perform a systematic review of patient- and tumour-related prognostic factors for post-RP UI. The primary outcome was UI within 3 mo after RP. Secondary outcomes included UI at 3–12 mo and ≥12 mo after RP. Evidence acquisition Databases including Medline, EMBASE, and CENTRAL were searched between January 1990 and May 2020. All studies reporting patient- and tumour-related prognostic factors in univariable or multivariable analyses were included. Surgical factors were excluded. Risk of bias (RoB) and confounding assessments were performed using the Quality In Prognosis Studies (QUIPS) tool. Random-effects meta-analyses were performed for all prognostic factor, where possible. Evidence synthesis A total of 119 studies (5 randomised controlled trials, 24 prospective, 88 retrospective, and 2 case-control studies) with 131 379 patients were included. RoB was high for study participation and confounding; moderate to high for statistical analysis, study attrition, and prognostic factor measurement; and low for outcome measurements. Significant prognostic factors for postoperative UI within 3 mo after RP were age (odds ratio [OR] per yearly increase 1.04, 95% confidence interval [CI] 1.03–1.05), membranous urethral length (MUL; OR per 1-mm increase 0.81, 95% CI 0.74–0.88), prostate volume (PV; OR per 1-ml increase 1.005, 95% CI 1.000–1.011), and Charlson comorbidity index (CCI; OR 1.28, 95% CI 1.09–1.50). Conclusions Increasing age, shorter MUL, greater PV, and higher CCI are independent prognostic factors for UI within 3 mo after RP, with all except CCI remaining prognostic at 3–12 mo. Patient summary We reviewed the literature to identify patient and disease factors associated with urinary incontinence after surgery for prostate cancer. We found increasing age, larger prostate volume, shorter length of a section of the urethra (membranous urethra), and lower fitness were associated with worse urinary incontinence for the first 3 mo after surgery, with all except lower fitness remaining predictive at 3–12 mo.

Context The impact of surgeon and hospital volume on outcomes after radical prostatectomy (RP) for localised prostate cancer (PCa) remains unknown. Objective To perform a systematic review on the association between surgeon or hospital volume and oncological and nononcological outcomes following RP for PCa. Evidence acquisition Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. All comparative studies for nonmetastatic PCa patients treated with RP published between January 1990 and May 2020 were included. For inclusion, studies had to compare hospital or surgeon volume, defined as caseload per unit time. Main outcomes included oncological (including prostate-specific antigen persistence, positive surgical margin [PSM], biochemical recurrence, local and distant recurrence, and cancer-specific and overall survival) and nononcological (perioperative complications including need for blood transfusion, conversion to open procedure and within 90-d death, and continence and erectile function) outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Both a narrative and a quantitative synthesis were planned if the data allowed. Evidence synthesis Sixty retrospective comparative studies were included. Generally, increasing surgeon and hospital volumes were associated with lower rates of mortality, PSM, adjuvant or salvage therapies, and perioperative complications. Combining group size cut-offs as used in the included studies, the median threshold for hospital volume at which outcomes start to diverge is 86 (interquartile range [IQR] 35–100) cases per year. In addition, above this threshold, the higher the caseload, the better the outcomes, especially for PSM. RoB and confounding were high for most domains. Conclusions Higher surgeon and hospital volumes for RP are associated with lower rates of PSMs, adjuvant or salvage therapies, and perioperative complications. This association becomes apparent from a caseload of >86 (IQR 35–100) per year and may further improve hereafter. Both high- and low-volume centres should measure their outcomes, make them publicly available, and improve their quality of care if needed. Patient summary We reviewed the literature to determine whether the number of prostate cancer operations (radical prostatectomy) performed in a hospital affects the outcomes of surgery. We found that, overall, hospitals with a higher number of operations per year have better outcomes in terms of cancer recurrence and complications during or after hospitalisation. However, it must be noted that surgeons working in hospitals with lower annual operations can still achieve similar or even better outcomes. Therefore, making hospital’s outcome data publicly available should be promoted internationally, so that patients can make an informed decision where they want to be treated.

Purpose Radiotherapy (RT) was identified as a risk factor for long-term cardiac effects in breast cancer patients treated until the 1990s. However, modern techniques reduce radiation exposure of the heart, but some exposure remains unavoidable. In a retrospective cohort study, we investigated cardiac mortality and morbidity of breast cancer survivors treated with recent RT in Germany. Methods A total of 11,982 breast cancer patients treated between 1998 and 2008 were included. A mortality follow-up was conducted until 06/2018. In order to assess cardiac morbidity occurring after breast cancer treatment, a questionnaire was sent out in 2014 and 2019. The effect of breast cancer laterality on cardiac mortality and morbidity was investigated as a proxy for radiation exposure. We used Cox Proportional Hazards regression analysis, taking potential confounders into account. Results After a median follow-up time of 11.1 years, there was no significant association of tumor laterality with cardiac mortality in irradiated patients (hazard ratio (HR) for left-sided versus right-sided tumor 1.09; 95% confidence interval (CI) 0.85–1.41). Furthermore, tumor laterality was not identified as a significant risk factor for cardiac morbidity (HR = 1.05; 95%CI 0.88–1.25). Conclusions Even though RT for left-sided breast cancer on average incurs higher radiation dose to the heart than RT for right-sided tumors, we found no evidence that laterality is a strong risk factor for cardiac disease after contemporary RT. However, larger sample sizes, longer follow-up, detailed information on individual risk factors and heart dose are needed to assess clinically manifest late effects of current cancer therapy.

Due to its low fractionation sensitivity, also known as “alpha/beta ratio,” in relation to its surrounding organs at risk, prostate cancer is predestined for hypofractionated radiation schedules assuming an increased therapeutic ratio compared to normofractionated regimens. While moderate hypofractionation (2.2–4 Gy) has been proven to be non-inferior to normal fractionation in several large randomized trials for localized prostate cancer, level I evidence for ultrahypofractionation (>4 Gy) was lacking until recently. An accumulating body of non-randomized evidence has recently been strengthened by the publication of two randomized studies comparing ultrahypofractionation with a normofractionated schedule, i.e., the Scandinavian HYPO-RT trial by Widmark et al. and the first toxicity results of the PACE‑B trial. In this review, we aim to give a brief overview of the current evidence of ultrahypofractionation, make an overall assessment of the level of evidence, and provide recommendations and requirements that should be followed before introducing ultrahypofractionation into routine clinical use.

ZusammenfassungBei der Therapie des metastasierten Prostatakarzinoms wurden in letzter Zeit deutliche Fortschritte erzielt. Zusätzlich zur Androgendeprivation stehen verschiedene Optionen zur Verfügung, wie gegen den Androgenrezeptor gerichtete Therapien und die Taxan-basierte Chemotherapie. Nach wie vor wird diskutiert, ob oligometastasierte Patienten primär nur systemisch behandelt werden sollten, ober ob sie von einer zusätzlichen Lokaltherapie des Primärtumors profitieren. Bis Mitte 2018 gab es keine evidenzbasierte Empfehlung, bei neu diagnostiziertem Prostatakarzinom mit Fernmetastasen eine lokale Bestrahlung der Prostata durchzuführen. Diese konnte als Einzelfallentscheidung aufgrund der Daten retrospektiver Serien indiziert werden. Dementsprechend gab es hierzu keine Empfehlungen in den Leitlinien. Durch die 2018 /19 publizierten Daten der STAMPEDE- und der HORRAD-Studie ist die Indikation zu einer lokalen Bestrahlung des Primärtumors beim oligometastasierten Prostatakarzinom mit weniger als 4 Knochenmetastasen nun klar belegt. Die folgende Übersicht fasst die Daten der beiden Studien zusammen, bewertet diese und gibt eine Empfehlung für den Einsatz der lokalen Strahlentherapie der Prostata in der oligometastasierten Situation.

Purpose Combined radioimmunotherapy (RIT) in follicular lymphomas (FL) has shown promising treatment efficacy in the Mabthera® and Involved field Radiation (MIR) study. Aim of this study was to analyze treatment efficacy and recurrence patterns after RIT in early-stage nodal and extranodal FL. Methods We reviewed 107 patients who were treated with combined RIT in two centers. Treatment consisted of 4 × rituximab followed by RIT with 4 × rituximab and involved field (IF) radiotherapy with 30/40 Gy. Median follow-up period was 71 months. In contrast to the MIR study, extranodal involvement and grade 3A histology were included in the analysis. Results Extranodal involvement and grade 3A histology were present in 21.8% and 13.1%, respectively. Overall response rate (ORR) after 4 × rituximab, after completion of RIT, and after 6 months was 78.1%, 98.8%, and 98.8%, respectively, with increasing rates of complete remissions (CR). Predictive factors associated with superior PFS were tumor size, completely excised lymphomas, and response to first 4 × rituximab. 5‑year PFS rate was 87.3%, with mostly outfield recurrences (94.1%). Second-line treatment was effective, with 53.3% CR and 46.7% partial remissions (PR). 5‑year OS was 98.1%. RIT was tolerated well, with mainly grade 1–2 acute side effects. Conclusion The real-world efficacy of RIT is comparable with the results of the MIR study. Additionally, this analysis shows that extranodal involvement and grade 3A histology are not associated with inferior PFS.

Purpose Active surveillance (AS) strategies for patients with low- and early intermediate-risk prostate cancer are still not consistently defined. Within a controlled randomized trial, active surveillance was compared to other treatment options for patients with prostate cancer. Aim of this analysis was to report on termination rates of patients treated with AS including different grade groups. Methods A randomized trial comparing radical prostatectomy, active surveillance, external beam radiotherapy and brachytherapy was performed from 2013 to 2016 and included 345 patients with low- and early intermediate-risk prostate cancer (ISUP grade groups 1 and 2). The trial was prematurely stopped due to slow accrual. A total of 130 patients were treated with active surveillance. Among them, 42 patients were diagnosed with intermediate-risk PCA. Reference pathology and AS quality control were performed throughout. Results After a median follow-up time of 18.8 months, 73 out of the 130 patients (56%) terminated active surveillance. Of these, 56 (77%) patients were histologically reclassified at the time of rebiopsy, including 35% and 60% of the grade group 1 and 2 patients, respectively. No patients who underwent radical prostatectomy at the time of reclassification had radical prostatectomy specimens ≥ grade group 3. Conclusion In this prospectively analyzed subcohort of patients with AS and conventional staging within a randomized trial, the 2-year histological reclassification rates were higher than those previously reported. Active surveillance may not be based on conventional staging alone, and patients with grade group 2 cancers may be recommended for active surveillance in carefully controlled trials only.

Purpose 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence. Methods We analyzed 68Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed. Results The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0–0.2 ng/ml, 0.21–0.3 ng/ml, and 0.31–0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease. Conclusions In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA

The original version of this article unfortunately contained a mistake. The copyright holder for this article was incorrectly given as “© Springer-Verlag GmbH Germany, part of Springer Nature 2021,” but should have been “© The Author(s) 2021.” The original article has been corrected.

Introduction68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only.Material and MethodsThis retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters.ResultsMedian follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= ConclusionThis analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT.

INTRODUCTION AND OBJECTIVE:Recently, a new prognostic model for patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP) has been proposed by the European Association of Uro...

Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1–3 (disagree), 4–6 (equivocal), 7–9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these, 33 (28%) statements achieved level 1 consensus and 49 (42%) statements achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time where further evidence is available to guide our approach, The authors would like to thank Peter E. Clark from Atrium Health, Levine Cancer Institute, Charlotte, NC, USA, for his contribution to the Delphi survey. Angela Corstorphine of Kstorfin Medical Communications Ltd provided medical writing support with the preparation of this manuscript; this support was funded jointly by EAU and ESMO.

Background: High-quality management of prostate cancer is needed in the fields of clinics, research, and education. Objective: The objective of this project was to develop the concept of “European Prostate Cancer Centres of Excellence” (EPCCE), with the specific aim of identifying European centres characterised by high-quality cancer care, research, and education. Design, setting, and participants: A task force of experts aimed at identifying the general criteria to define the EPCCE. Discussion took place in conference calls and by e-mail from March 2017 to November 2017, and the final consensus meeting named “European Association of Urology (EAU) Prostate Cancer Centre Consensus Meeting” was held in Barcelona on November 16, 2017. Outcome measurements and statistical analysis: The required criteria were grouped into three main steps: (1) clinics, (2) research, and (3) education. A quality control approach for the three steps was defined. Results and limitations: The definition of EPCCE consisted of the following steps: (1) clinical step—five items were identified and classified as core team, associated services, multidisciplinary approach, diagnostic pathway, and therapeutic pathway; (2) research step—internal monitoring of outcomes was required; clinical data had to be collected through a prespecified database, clinical outcomes had to be periodically assessed, and prospective trials had to be conducted; (3) educational step—it consists of structured fellowship programmes of 1 yr, including 6 mo of research and 6 mo of clinics; and (4) quality assurance and quality control procedures, related to the quality assessment of the previous three steps. A limitation of this project was that the definition of standards and items was mainly based on a consensus among experts rather than being an evidence-based process. Conclusions: The EAU Prostate Cancer Centre Consensus Meeting defined the criteria for the identification of the EPCCE in the fields of clinics, research, and education. The inclusion of a quality control approach represents the novelty that supports the excellence of these centres. Patient summary: A task force of experts defined the criteria for the identification of European Prostate Cancer Centres of Excellence, in order to certify the high-quality centres for prostate cancer management. The European Association of Urology Prostate Cancer Centre Consensus Meeting defined the criteria for the identification of European Prostate Cancer Centres of Excellence in the field of clinics, research, and education. The inclusion of a quality control approach represents the novelty that supports the excellence of these centres.

OBJECTIVE To test whether salvage radiotherapy (SRT) in patients with lymph node negative (N0) prostate cancer is equally effective with persistent prostate-specific antigen (PSA) and PSA rising from the undetectable range (

For a patient suffering from non-metastatic prostate cancer, the individualized recommendation of radiotherapy has to be the fruit of a multidisciplinary approach in the context of a Tumor Board, to be explained carefully to the patient to obtain his informed consent. External beam radiotherapy is now delivered by intensity modulated radiotherapy, considered as the gold standard. From a radiotherapy perspective, low-risk localized prostate cancer is treated by image guided intensity modulated radiotherapy, or brachytherapy if patients meet the required eligibility criteria. Intermediate-risk patients may benefit from intensity modulated radiotherapy combined with 4–6 months of androgen deprivation therapy; intensity modulated radiotherapy alone or combined with brachytherapy can be offered to patients unsuitable for androgen deprivation therapy due to co-morbidities or unwilling to accept it to preserve their sexual health. High-risk prostate cancer, i.e. high-risk localized and locally advanced prostate cancer, requires intensity modulated radiotherapy with long-term (≥2 years) androgen deprivation therapy with luteinizing hormone releasing hormone agonists. Post-operative irradiation, either immediate or early deferred, is proposed to patients classified as pT3pN0, based on surgical margins, prostate-specific antigen values and quality of life. Whatever the techniques and their degree of sophistication, quality assurance plays a major role in the management of radiotherapy, requiring the involvement of physicians, physicists, dosimetrists, radiation technologists and computer scientists. The patients must be informed about the potential morbidity of radiotherapy and androgen deprivation therapy and followed regularly during and after treatment for tertiary prevention and evaluation. A close cooperation is needed with general practitioners and specialists to prevent and mitigate side effects and maintain quality of life. Keywords: Localized prostate cancer, Locally advanced prostate cancer, Brachytherapy, Intensity modulated radiotherapy, Short-term and long-term androgen deprivation therapy

Die primare perkutane Strahlentherapie mit oder ohne begleitende Hormontherapie bildet eine der Behandlungsoptionen beim Prostatakarzinom der intermediaren Risikogruppe. Es soll eine kurze Ubersicht der derzeit noch unterschiedlichen Behandlungsansatze im Rahmen der definitiven perkutanen Strahlentherapie gegeben werden. Es erfolgte eine Sichtung der aktuellen Leitlinien und eine Literaturrecherche via PubMed-Datenbank. Es existieren verschiedene Empfehlungen zur Einteilung in Risikogruppen beim lokalisierten Prostatakarzinom. Um der Heterogenitat der intermediaren Risikogruppe Rechnung zu tragen, scheint die Untergruppierung in ein gunstiges und ungunstiges Stadium, einen sinnvollen Ansatz zur Individualisierung der Therapie darzustellen. Randomisierte Studien konnten auch bei Patienten der intermediaren Risikogruppe eine Verbesserung der Therapieergebnisse bei Kombination von Strahlentherapie und Hormontherapie nachweisen. Zeitgleich erhoht der Einsatz der Hormontherapie die Rate an Nebenwirkungen und sollte daher individuell gepruft werden. Die Anwendung der alleinigen dosiseskalierten Strahlentherapie scheint insbesondere bei gunstigerem intermediaren Risikoprofil eine gleichwertige therapeutische Option darzustellen. Bei gunstigerem Risikoprofil scheint eine alleinige dosiseskalierte Strahlentherapie und bei ungunstigem intermediaren Risikoprofil die Kombination mit kurzzeitiger (4–6 Monate) Hormontherapie eine sinnvolle Therapiestrategie zu sein. Weitere Evidenz zu dieser Fragestellung werden die noch ausstehenden Ergebnisse der RTOG-0815-Studie bieten.

Die Salvage-Strahlentherapie (SRT) ist Standard bei Patienten mit biochemischem Progress nach Prostatektomie im primaren Stadium pN0. Randomisierte Studien haben nun den Nutzen einer zusatzlichen Androgendeprivationstherapie (ADT) untersucht. Eine evidenzbasierte, systematische Ubersicht uber die Kombination einer ADT mit einer SRT bei rezidiviertem Prostatakarzinom soll erstellt werden. Die verfugbare Literatur wurde ausgewertet und daraus Behandlungsempfehlungen unter Berucksichtigung von Risikoprofilen abgeleitet. Es liegen die Ergebnisse von zwei randomisierten und mehreren retrospektiven Analysen vor. Die RTOG-9601-Studie zeigte eine Verbesserung des Gesamtuberlebens und des tumorspezifischen Uberlebens durch die Kombination von 24 Monaten Bicalutamid 150 mg/Tag und SRT im Vergleich zur alleinigen SRT. Dieser Vorteil war jedoch nur bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT, einem Gleason-Score 7 oder positivem Schnittrand nachweisbar. Die GETUG-AFU-16-Studie zeigte lediglich eine Verbesserung des progressionsfreien Uberlebens (PFS) durch die zusatzliche Gabe von 6 Monaten Goserelin zur SRT. In beiden Studien wurde keine Zunahme schwerer Spatfolgen durch die ADT beobachtet. Retrospektive Studien deuten darauf hin, dass eine zusatzliche ADT das PFS bei Hochrisikopatienten verbessert. Bei Patienten mit PSA-Werten ≥0,7 ng/ml vor SRT verbessert eine ADT zur SRT das Gesamtuberleben. Beim PSA-Wert

Der Anteil der Patienten mit lokal fortgeschrittenem oder (oligo)metastasiertem Prostatakarzinom (PCa) hat in den letzten Jahren zugenommen. Im Vergleich zu Patienten mit lokalisiertem PCa ist ohne eine Lokaltherapie das Risiko lokaler Komplikationen hoher und die onkologischen Ergebnisse schlechter. Der Stellenwert der radikalen Prostatektomie (RP) bei klinisch lokal fortgeschrittenem oder metastasiertem Prostatakarzinom wird erortert. Es erfolgten eine systematische Literaturrecherche und Zusammenstellung relevanter Artikel aus PubMed und Medline. Aktuelle Leitlinien empfehlen die RP als eine der Behandlungsoptionen bei Patienten mit lokal fortgeschrittenem PCa. Die Durchfuhrung einer RP bei Patienten mit metastasiertem PCa hingegen sollte nur innerhalb klinischer Studien durchgefuhrt werden. Im Vergleich zu Patienten ohne eine lokale Behandlung verringert die RP das Risiko lokaler Komplikationen deutlich. Wahrend beim lokal fortgeschrittenen PCa ein klarer onkologischer Nutzen fur die RP gezeigt werden konnte, ist der Nutzen bei Patienten mit metastasierten Erkrankungen immer noch umstritten. Aufgrund schwierigerer Operationsbedingungen und einer erhohten Wahrscheinlichkeit fur ein multimodales Therapiekonzept werden in der Literatur eine hohere perioperative Morbiditat und schlechtere funktionelle Ergebnisse im Vergleich zu Patienten mit lokalisiertem PCa berichtet. Wahrend die RP fur Patienten mit lokal fortgeschrittenem PCa genauso wie im lokalisierten Stadium durchgefuhrt werden kann, muss der Nutzen bei Vorliegen einer metastasierten Erkrankung weiter geklart werden. Alle Patienten, die sich einer RP unterziehen, mussen besonders im Hinblick auf das mogliche schlechtere funktionelle Ergebnis beraten werden.

PURPOSE Adjuvant compared with early salvage radiation therapy (sRT) following radical prostatectomy (RP) has not been shown to reduce progression-free survival in randomized controlled trials. However, these trials might have missed a benefit in men with adverse pathology at RP given that these men were under-represented and immortal time bias might have been present; herein, we investigate this possibility. METHODS We evaluated the impact of adjuvant versus early sRT on all-cause mortality (ACM) risk in men with adverse pathology defined as positive pelvic lymph nodes (pN1) or pGleason score 8-10 prostate cancer (PC) and disease extending beyond the prostate (pT3/4). We used a treatment propensity score to minimize potential treatment selection bias when estimating the causal effect of adjuvant versus early sRT on ACM risk and a sensitivity analysis to assess the impact that varying definitions of adverse pathology had on ACM risk adjusting for age at RP, PC prognostic factors, site, and the time-dependent use of post-RP androgen deprivation therapy. RESULTS After a median follow-up (interquartile range) of 8.16 (6.00-12.10) years, of the 26,118 men in the study cohort, 2,104 (8.06%) died, of which 539 (25.62%) were from PC. After excluding men with a persistent prostate-specific antigen, adjuvant compared with early sRT was associated with a significantly lower ACM risk among men with adverse pathology at RP when men with pN1 PC were excluded (0.33 [0.13-0.85]; P = .02) or included (0.66 [0.44-0.99]; P = .04). CONCLUSION Adjuvant radiation therapy should be considered in men with pN1 or pGleason score 8 to 10 and pT3/4 PC given the possibility that a significant reduction in ACM risk exists.

Context The clinical effectiveness of focal therapy (FT) for localised prostate cancer (PCa) remains controversial. Objective To analyse the evidence base for primary FT for localised PCa via a systematic review (SR) to formulate clinical practice recommendations. Evidence acquisition A protocol-driven, PRISMA-adhering SR comparing primary FT (sub-total, focal, hemi-gland, or partial ablation) versus standard options (active surveillance [AS], radical prostatectomy [RP], or external beam radiotherapy [EBRT]) was undertaken. Only comparative studies with ≥50 patients per arm were included. Primary outcomes included oncological, functional, and quality-of-life outcomes. Risk of bias (RoB) and confounding assessments were undertaken. Eligible SRs were reviewed and appraised (AMSTAR) and ongoing prospective comparative studies were summarised. Evidence synthesis Out of 1119 articles identified, four primary studies (1 randomised controlled trial [RCT] and 3 retrospective studies) recruiting 3961 patients and ten eligible SRs were identified. Only qualitative synthesis was possible owing to clinical heterogeneity. Overall, RoB and confounding were moderate to high. An RCT comparing vascular-targeted focal photodynamic therapy (PDT) with AS found a significantly lower rate of treatment failure at 2 yr with PDT. There were no differences in functional outcomes, although PDT was associated with worse transient adverse events. However, the external validity of the study was contentious. A retrospective study comparing focal HIFU with robotic RP found no significant differences in treatment failure at 3 yr, with focal HIFU having better continence and erectile function recovery. Two retrospective cohort studies using Surveillance, Epidemiology and End Results data compared focal laser ablation (FLA) against RP and EBRT, reporting significantly worse oncological outcomes for FLA. The overall data quality and applicability of the primary studies were limited because of clinical heterogeneity, RoB and confounding, lack of long-term data, inappropriate outcome measures, and poor external validity. Virtually all the SRs identified concluded that there was insufficient high-certainty evidence to make definitive conclusions regarding the clinical effectiveness of FT, with the majority of SRs judged to have a low or critically low confidence rating. Eight ongoing prospective comparative studies were identified. Ways of improving the evidence base are discussed. Conclusions The certainty of the evidence regarding the comparative effectiveness of FT as a primary treatment for localised PCa was low, with significant uncertainties. Until higher-certainty evidence emerges from robust prospective comparative studies measuring clinically meaningful outcomes at long-term time points, FT should ideally be performed within clinical trials or well-designed prospective cohort studies. Patient summary We examined the literature to determine the effectiveness of prostate-targeted treatment compared with standard treatments for untreated localised prostate cancer. There was no strong evidence showing that focal treatment compares favourably with standard treatments; consequently, focal treatment is not recommended for routine standard practice.

Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90% within a follow-up of 1–2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.

Background Prostate cancer is the most frequently occurring malignancy among men in Germany, with 60 000 new cases each year. Three of every four tumors are detected at an early, localized stage, when various curative treatment strategies are possible. Methods A selective search of the literature in PubMed accompanied by consideration of guidelines from Germany and other countries. Results Owing to the usually prolonged natural course of localized prostate cancer, local treatment is recommended for patients with a life expectancy of at least 10 years. The established treatments with curative intent are radical prostatectomy, percutaneous radiotherapy, and brachytherapy, with active surveillance as a further option for patients with low-risk disease. The eventual choice of treatment is determined by tumor stage, risk group, comorbidities, and patient preference. Conversations with the patient must cover not only the oncological outcome but also the potential adverse effects of the different treatment options. Depending on the procedure, urinary incontinence, erectile dysfunction, and inflammation of the bladder and/or rectum may be frequently occurring complications. Conclusion A number of curative and other treatments are available for patients with localized prostate cancer. The goal is to identify the appropriate option for each individual patient by means of detailed discussion.

Context Surgical techniques aimed at preserving the neurovascular bundles during radical prostatectomy (RP) have been proposed to improve functional outcomes. However, it remains unclear if nerve-sparing (NS) surgery adversely affects oncological metrics. Objective To explore the oncological safety of NS versus non-NS (NNS) surgery and to identify factors affecting the oncological outcomes of NS surgery. Evidence acquisition Relevant databases were searched for English language articles published between January 1, 1990 and May 8, 2020. Comparative studies for patients with nonmetastatic prostate cancer (PCa) treated with primary RP were included. NS and NNS techniques were compared. The main outcomes were side-specific positive surgical margins (ssPSM) and biochemical recurrence (BCR). Risk of bias (RoB) and confounding assessments were performed. Evidence synthesis Out of 1573 articles identified, 18 studies recruiting a total of 21 654 patients were included. The overall RoB and confounding were high across all domains. The most common selection criteria for NS RP identified were characteristic of low-risk disease, including low core-biopsy involvement. Seven studies evaluated the link with ssPSM and showed an increase in ssPSM after adjustment for side-specific confounders, with the relative risk for NS RP ranging from 1.50 to 1.53. Thirteen papers assessing BCR showed no difference in outcomes with at least 12 mo of follow-up. Lack of data prevented any subgroup analysis for potentially important variables. The definitions of NS were heterogeneous and poorly described in most studies. Conclusions Current data revealed an association between NS surgery and an increase in the risk of ssPSM. This did not translate into a negative impact on BCR, although follow-up was short and many men harbored low-risk PCa. There are significant knowledge gaps in terms of how various patient, disease, and surgical factors affect outcomes. Adequately powered and well-designed prospective trials and cohort studies accounting for these issues with long-term follow-up are recommended. Patient summary Neurovascular bundles (NVBs) are structures containing nerves and blood vessels. The NVBs close to the prostate are responsible for erections. We reviewed the literature to determine if a technique to preserve the NVBs during removal of the prostate causes worse cancer outcomes. We found that NVB preservation was poorly defined but, if applied, was associated with a higher risk of cancer at the margins of the tissue removed, even in patients with low-risk prostate cancer. The long-term importance of this finding for patients is unclear. More data are needed to provide recommendations.

ZusammenfassungDie Weiterentwicklung systemischer Therapiekonzepte beim metastasierten Prostatakarzinom haben in der jüngeren Vergangenheit zu einer deutlichen Prognoseverbesserung geführt. Inwieweit durch lokale und/oder gezielte Metastasen-gerichtete Therapien neben Palliation, lokaler Kontrolle und Funktionserhalt ein zusätzlicher prognostischer Nutzen besteht, war lange unklar. Für die lokale Therapie der Prostata besteht aktuell die höchste Evidenz für die Strahlentherapie und zeigt bei „niedriger Metastasen-Tumorlast“ oligometastasierter Patienten einen signifikanten Überlebensvorteil. Metastasen-gerichtete operative oder radioonkologische Konzepte zeigen ebenfalls Möglichkeiten zur Verbesserung der Prognose auf, sind bislang aber noch unzureichend untersucht und sollten daher immer individuell und interdisziplinär diskutiert, dokumentiert und etabliert werden.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on screening, diagnosis, and local treatment of clinically localised prostate cancer (PCa). Evidence acquisition: The panel performed a literature review of new data, covering the time frame between 2016 and 2020. The guidelines were updated and a strength rating for each recommendation was added based on a systematic review of the evidence. Evidence synthesis: A risk-adapted strategy for identifying men who may develop PCa is advised, generally commencing at 50 yr of age and based on individualised life expectancy. Risk-adapted screening should be offered to men at increased risk from the age of 45 yr and to breast cancer susceptibility gene (BRCA) mutation carriers, who have been confirmed to be at risk of early and aggressive disease (mainly BRAC2), from around 40 yr of age. The use of multiparametric magnetic resonance imaging in order to avoid unnecessary biopsies is recommended. When a biopsy is performed, a combination of targeted and systematic biopsies must be offered. There is currently no place for the routine use of tissue-based biomarkers. Whilst prostate-specific membrane antigen positron emission tomography computed tomography is the most sensitive staging procedure, the lack of outcome benefit remains a major limitation. Active surveillance (AS) should always be discussed with low-risk patients, as well as with selected intermediate-risk patients with favourable International Society of Urological Pathology (ISUP) 2 lesions. Local therapies are addressed, as well as the AS journey and the management of persistent prostate-specific antigen after surgery. A strong recommendation to consider moderate hypofractionation in intermediate-risk patients is provided. Patients with cN1 PCa should be offered a local treatment combined with long-term hormonal treatment. Conclusions: The evidence in the field of diagnosis, staging, and treatment of localised PCa is evolving rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for their use in clinical practice. These PCa guidelines reflect the multidisciplinary nature of PCa management. Patient summary: Updated prostate cancer guidelines are presented, addressing screening, diagnosis, and local treatment with curative intent. These guidelines rely on the available scientific evidence, and new insights will need to be considered and included on a regular basis. In some cases, the supporting evidence for new treatment options is not yet strong enough to provide a recommendation, which is why continuous updating is important. Patients must be fully informed of all relevant options and, together with their treating physicians, decide on the most optimal management for them. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy and Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer (PCa) summarise the most recent findings and provide recommendations for clinical practice, addressing screening, diagnosis, and local treatment with curative intent. Key stakeholders in PCa management were involved in their development, including a patient representative. A full version is available at the EAU office and online at http://uroweb.org/guideline/prostate-cancer/. A separate publication will address the management of relapsing-, metastatic-, and castration-resistant PCa.

Purpose Various randomized phase III clinical trials have compared moderately hypofractionated to normofractionated radiotherapy (RT). These modalities showed similar effectiveness without major differences in toxicity. This project was conducted by the Prostate Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) and the Working Party on Radiation Oncology of the German Cancer Society. We aimed to investigate expert opinions on the use of moderately hypofractionated RT as a definitive treatment for localized prostate cancer in German-speaking countries. Methods A 25-item, web-based questionnaire on moderate-hypofractionation RT was prepared by an internal committee. The experts of the DEGRO were asked to complete the questionnaire. Results Fourteen active members of DEGRO completed the questionnaire. The questions described indications for selecting patients eligible to receive moderate hypofractionation based on clinical and pathological factors such as age, urinary symptoms, and risk-group. The questions also collected information on the technical aspects of selection criteria, including the definition of a clinical target volume, the use of imaging, protocols for bladder and rectal filling, the choice of a fractionation schedule, and the use of image guidance. Moreover, the questionnaire collected information on post-treatment surveillance after applying moderately hypofractionated RT. Conclusion Although opinions varied on the use of moderate-hypofractionation RT, the current survey reflected broad agreement on the notion that moderately hypofractionated RT could be considered a standard treatment for localized prostate cancer in German-speaking countries.

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.

Context The prognosis and optimal management of pN0/pN1 patients with persistently elevated prostate-specific antigen (PSA) 6–8 wk after radical prostatectomy (RP) remain unclear. Objective To perform a systematic review of oncologic outcomes and effectiveness of salvage therapies in men with a detectable PSA level after RP. Evidence acquisition A systematic review was performed in May 2020. A total of 2374 articles were screened, and 25 studies including 5217 men were selected and included in the systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Evidence synthesis PSA persistence was most commonly defined as PSA >0.1 ng/ml. PSA persistence was significantly correlated with disease aggressiveness and associated with worse oncologic outcomes than in men with undetectable PSA levels. The 5-yr recurrence-free survival rates varied from 21.5% to 67.0%. The ≥10-yr cancer-specific survival was 75–88%. Salvage radiotherapy ± androgen deprivation therapy was associated with improved survival outcomes. Risk stratification according to pathologic features, PSA levels/kinetics, and genomic classifier may aid in personalization of treatment. The usefulness of molecular imaging in this setting remains underevaluated. Main limitations of this systematic review are the retrospective design of the included studies and the lack of randomized controlled trials (RCTs) focusing on this specific population. Conclusions PSA persistence after RP is strongly correlated with poor oncologic outcomes. Our review suggests a benefit from immediate radiotherapy; however, current evidence is still low. Indication of subsequent therapies should be based on individual discussions, taking into account all the prognostic factors and the efficacy/toxicity imbalance of proposed treatment. Results from ongoing RCTs are awaited to state on the role of more intensified systemic therapy in this population. Patient summary Patients with a detectable prostate-specific antigen level after surgery are at high risk of subsequent progression. Immediate radiotherapy might improve survival outcomes. Further research into the role of molecular imaging and genomic classifier is needed in this patient population.

Objective: To present a summary of the 2020 version of the European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on the treatment of relapsing, metastatic, and castration-resistant prostate cancer (CRPC). Evidence acquisition: The working panel performed a literature review of the new data (2016–2019). The guidelines were updated, and the levels of evidence and/or grades of recommendation were added based on a systematic review of the literature. Evidence synthesis: Prostate-specific membrane antigen positron emission tomography computed tomography scanning has developed an increasingly important role in men with biochemical recurrence after local therapy. Early salvage radiotherapy after radical prostatectomy appears as effective as adjuvant radiotherapy and, in a subset of patients, should be combined with androgen deprivation. New treatments have become available for men with metastatic hormone-sensitive prostate cancer (PCa), nonmetastatic CRPC, and metastatic CRPC, along with a role for local radiotherapy in men with low-volume metastatic hormone-sensitive PCa. Also included is information on quality of life outcomes in men with PCa. Conclusions: The knowledge in the field of advanced and metastatic PCa and CRPC is changing rapidly. The 2020 EAU-EANM-ESTRO-ESUR-SIOG guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/). Patient summary: This article summarises the guidelines for the treatment of relapsing, metastatic, and castration-resistant prostate cancer. These guidelines are evidence based and guide the clinician in the discussion with the patient on the treatment decisions to be taken. These guidelines are updated every year; this summary spans the 2017–2020 period of new evidence. The knowledge in the field of advanced and metastatic prostate cancer (PCa) and castration-resistant prostate cancer is changing rapidly. The 2020 European Association of Urology (EAU)-European Association of Nuclear Medicine (EANM)-European Society for Radiotherapy & Oncology (ESTRO)-European Society of Urogenital Radiology (ESUR)-International Society of Geriatric Oncology (SIOG) guidelines on PCa summarise the most recent findings and advice for use in clinical practice. These PCa guidelines are first endorsed by the EANM and reflect the multidisciplinary nature of PCa management. A full version is available from the EAU office or online (http://uroweb.org/guideline/prostate-cancer/).

INTRODUCTION AND OBJECTIVE:A rapidly changing scenario in the management of patients with PSA rising after radical prostatectomy (RP) may have determined different patterns of salvage radiation the...

INTRODUCTION AND OBJECTIVE:Salvage radiation therapy (SRT) represents a curative treatment option for patients with prostate-specific antigen (PSA) rise after radical prostatectomy (RP). However, a...

INTRODUCTION AND OBJECTIVE:Salvage radiotherapy (SRT) may lead to better oncologic outcomes in prostate cancer (PCa) patients who develop biochemical recurrence (BCR) after radical prostatectomy (R...

INTRODUCTION AND OBJECTIVE:Patients treated with post-prostatectomy radiation therapy (RT) are exposed to a potential risk of genitourinary (GU) and gastrointestinal (GI) toxicity. However, it is s...

INTRODUCTION AND OBJECTIVE:Recently, a new risk stratification of patients harboring biochemical recurrence (BCR) after radical prostatectomy (RP) has been proposed by the EAU: EAU low-risk BCR (Gl...

Biochemical recurrence (BCR) after primary treatment of localized prostate cancer does not necessarily lead to clinically apparent progressive disease. To aid in prognostication, the European Association of Urology prostate cancer guidelines panel undertook a systematic review and successfully developed a novel BCR risk stratification system (groups with a low risk or high risk of BCR) based on disease and prostate-specific antigen characteristics. Patient summary: Following treatment to cure prostate cancer, some patients can develop recurrence of disease identified via a prostate-specific antigen blood test (ie, biochemical recurrence, or BCR). However, not every man who experiences BCR develops progressive disease (symptoms or evidence of disease progression on imaging). We conducted a review of the literature and developed a classification system for predicting which patients might progress to optimize treatment decisions. The EAU-EANM-ESTRO-ESUR-SIOG prostate cancer guidelines panel recommends stratifying patients experiencing biochemical recurrence (BCR) after primary treatment for localized prostate cancer into EAU low-risk and high-risk BCR groups. Each patient's risk profile and life expectancy should be considered when discussing the benefits and toxicities of salvage treatments.