ESTRO 2022

Session Item

Urology

Session Type: Poster (digital)

Track: Clinical

Journey:

Results of a concept-development for a phase III trial on radiotherapy in primary prostate cancer

Simon KB Spohn, Germany

Presentation Number: PO-1414

Abstract

Abstract Title:

Results of a concept-development for a phase III trial on radiotherapy in primary prostate cancer

Authors:

Simon Spohn^1,2, Sonja Adebahr¹, Maria Huber³, Carolin Jenkner³, Rolf Wiehle⁴, Blin Nagavci⁵, Christine Schmucker⁶, Ernst Carl⁷, Ronald Chen⁸, Wolfgang Weber⁹, Michael Mix¹⁰, Alexander Rühle¹, Nils Nicolay¹, Christian Gratzke¹¹, Matthias Benndorf¹², Thomas Wiegel¹³, Joachim Weis¹⁴, Dimos Baltas⁴, Constantinos Zamboglou^1,2,15, Anca Grosu¹

¹University Medical Center Freiburg, Department of Radiation Oncology, Freiburg, Germany; ²Faculty of Medicine, Berta-Ottenstein-Programme, Freiburg, Germany; ³Faculty of Medicine and Medical Center, Clinical Trials Unit, Freiburg, Germany; ⁴University Medical Center Freiburg, Division of Medical Physics - Department of Radiation Oncology, Freiburg, Germany; ⁵University Medical Center Freiburg, Institute for Evidence in Medicine, Freiburg, Germany; ⁶University Medical Center, Institute for Evidence in Medicine, Freiburg, Germany; ⁷Bundesverband Prostatakrebs Selbsthilfe e.V., Bundesverband Prostatakrebs Selbsthilfe e.V., Bonn, Germany; ⁸University of Kansas Cancer Center, Department of Radiation Oncology, Kansas City KS 5, USA; ⁹Klinikum rechts der Isar - Technical University of Munich, Department of Nuclear Medicine, Munich, Germany; ¹⁰University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg, Germany; ¹¹University Medical Center Freiburg, Department of Urology, Freiburg, Germany; ¹²University Medical Center Freiburg, Department of Radiology, Freiburg, Germany; ¹³University Hospital Ulm, Department of Radiation Oncology, Ulm, Germany; ¹⁴Comprehensive Cancer Center - University Medical Center Freiburg, Department of Cancer Self-Help Research, Freiburg, Germany; ¹⁵European University of Cyprus, German Oncology Center, Limassol, Cyprus

Show Affiliations

Purpose or 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).

Material and Methods

The one year 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.