Stereotactic radiotherapy (Cyberknife®), proton beam therapy and irreversible (electroporation Nanoknife®) for localised prostate cancer (PCa): a systematic review. Update 2024

Duration: 02/2024 – 07/2024
Language: English (with German summary)
Publication: HTA Project Report No.: 107/1. Update: https://eprints.aihta.at/1530/

Background:
Prostate cancer is the leading cause of cancer in men in Austria accounting for 23% of all new cancer incidence cases. In 2022, 1,417 men were diagnosed with malignant prostate tumours. with an incidence of 115,3/100.000 and a mortality of 24,5/100.000 men.  Patients with localized prostate cancer (where cancer is confined to the prostate gland, in the absence of lymph node invasion or metastases, corresponding to stage N0M0) can be defined as low-risk (clinical stage T1-T2a), intermediate-risk (clinical stage T2b) or high risk (clinical stage T2c). The primary goal of treating clinically confined localized prostate cancer is to target men most likely to need intervention to prevent disability or death while minimizing intervention-related complications.

Possible treatment options include:

• Surgery: Radical prostatectomy (incl. laparoscopic or robotic-assisted prostatectomy)
• Radiotherapy: External radiotherapy (including conventional radiotherapy, moderately hypofractionated radiotherapy, extremely hypofractionated radiotherapy or stereotactic radiotherapy (SBRT) and proton therapy (PT)), which is used with the support of image guided radiation therapy (IGRT)
• Interstitial brachytherapy (BT): internal radiotherapy
• Cryotherapy
• Hormonal therapy 
• High-intensity focused ultrasound (HIFU)
• Irreversible Electroporation (NanoKnife®)
• Observation: Watchful waiting, Active surveillance

Treatment options in focus of this project

Radiotherapy:   External beam radiation therapy (EBRT) is used as definitive therapy in patients with early and locally advanced disease and intensity-modulated radiation therapy (IMRT) has become the standard method for definitive external radiation to the prostate to treat PCa.

1. Stereotactic radiotherapy (SBRT) involves delivering a high dose of radiation very precisely to a tumor, but with fewer treatments (fractions) than IMRT. Standard EBRT is delivered in 1.8- to 2-Gy fractions per day to a typical dose of 74-80 Gy; In SBRT hypofractionated regimens are given over a shorter period of time (fewer days or weeks) and can deliver daily fractions of 2.5-10 Gy. The Cyberknife® (equivalent of the Gamma Knife®, designed only to treat cancer above the ear and in the cervical spine) is a linear accelerator which delivers the SBRT beams to any part of the body from any direction, using robotic arms. Cyberknife® typically uses photon therapy.
2. Proton (beam) therapy (PT or PBT) is another type of EBRT using ionizing radiation precisely releasing the high-dosed radiation to the tumor. Proton therapy is delivered in a series of fractions (as with SBRT) via a cyclotron or synchrotron (MedAustron) and it designed to decrease radiation exposure to normal tissues.

Minimally invasive, non-thermal tissue ablation technique     

1. Irreversible electroporation (IRE, NanoKnife®) is a relatively new alternative treatment, which involves inserting needles into and around the cancer. It uses short, repetitive, non-thermal high-energy pulses of electricity to destroy the cancer cells. It is performed under

general anesthetic and takes 2 to 4 hours.

Project Objectives: The project aims to assess the relative effectiveness and safety of 3 interventions for the therapy of localized prostate cancer: (i) stereotactic body radiation therapy (x-ray or photon based) and (ii) the particle-based proton beam therapy and (iii) irreversible electroporation.

Research Question:

• 
  Is stereotactic body radiation therapy (Cyberknife®) or proton beam therapy or irreversible electroporation (e.g., with NanoKnife®) more effective (survival, disease progression, health-related quality of life) and safer (toxicity and other side-effects) than alternative prostate cancer-specific treatment options (e.g. surgery, watchful waiting, internal radiotherapy, other types of external beam radiotherapy) for localized prostate cancer?

Inclusion criteria (PICO) [1]:

Methods: Systematic literature search in 4 databases and 1 clinical trial registry:

1. INAHTA Database
2. Cochrane Library
3. Medline via Ovid
4. Embase
5. ClinicalTrials.gov.

Search limited to studies published in German or English since February 2018.

Literature Selection: Abstract and full text literature selection is conducted by 2 reviewers (LC, IR). First reviewer screens all abstracts, the second reviewer only the excluded studies The literature selection process will be presented via a PRISMA diagram.

• If no SRs can be identified, or available SRs require updating, primary studies will be searched in the databases listed above.

Data extraction: The following data will be extracted: study details (author, country, setting, number of patients, length of follow-up), patient characteristics (tumour stage, risk category, Gleason score, loss to follow-up), intervention characteristics (technique, radiation dose, dose per fraction, etc.), outcomes (as defined in the PICO table above). Data will be extracted by the first reviewer (JE) and checked by the second reviewer (LS).

Risk of bias and strength of evidence: Risk of bias assessment will be conducted by two researchers (JE, LS) using the appropriate Risk of Bias Tool (https://www.latitudes-network.org/)

Data synthesis: The outcomes will be reported as qualitative evidence synthesis.

Time schedule/ milestones:

References:
Schmidt, L. and Lohr, P. and Wild, C. (2018): Stereotactic radiotherapy, proton therapy and irreversible electroporation for the treatment of localised prostate cancer. HTA-Projektbericht 107. https://eprints.aihta.at/1165/