HTA of Cyberknife, proton beam therapy and Nanoknife for prostate cancer in Austria

In mid-August 2018, the Austrian HTA body, the Ludwig-Boltzmann Institute (LBI), has published a health technology assessment in which they have assessed the efficacy and safety of stereotactic radiotherapy (Cyberknife®), proton beam therapy and irreversible electroporation (Nanoknife®) for localized prostate cancer (PCa).

Prostate cancer is the leading cause of cancer in men in Austria accounting for 23% of all new cancer incidence cases. The primary objective of treating clinically confined localized PCa is to target males most likely to need intervention to prevent disability or death while minimizing intervention-related complications. There are many possible treatment options, but this report of the LBI focuses on assessing the relative effectiveness and safety of the following three methods:

• Stereotactic radiotherapy (SBRT), which involves delivering a high dose of radiation very precisely to a tumour, but with fewer fractions compared to than intensity-modulated radiation therapy. 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 (compared with the standard External beam radiation therapy, EBRT). The Cyberknife® (the equivalent of the Gamma Knife®, designed only to treat cancer above the ear and in the cervical spine) is a linear accelerator which provides the SBRT beams to any part of the body from any direction, using robotic arms. Cyberknife® typically uses photon therapy
• Proton (beam) therapy (PT) is another type of EBRT using ionizing radiation by precisely releasing the high-dose radiation to a tumour. Proton therapy is delivered in a series of fractions (as with SBRT) via a cyclotron or synchrotron (MedAustron) and is designed to decrease radiation exposure to healthy tissues
• Minimally invasive, non-thermal tissue ablation technique - irreversible electroporation (IRE, NanoKnife®), which is a relatively new alternative treatment, which involves inserting needles into and around 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

The authors’ goal was to assess whether the abovementioned methods are more effective (disease progression, survival, 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, different types of external beam radiotherapy) for localized prostate cancer.

The authors have performed a systematic review of the literature obtained from the following databases: Cochrane library, Centre for Research and Dissemination (DARE, NHS-EED, HTA), Clinical Trial Registries, Embase, Medline via Ovid. The authors searched for publications published after 2010, only in German and English. Eventually, eight (8) publications with five (5) Controlled interventional studies, 14 publications with 12 Non-controlled prospective studies with ≥50 patients, two (2) systematic reviews and one (1) HTA report were included in this report.

Results

Due to lack of RCT evidence, no conclusions regarding the effectiveness of IRE or SBRT were possible. The results of the five (5) RCTs regarding PT provided inconsistent results. Thus the authors declare the quality of evidence to be moderate-low and could not make a conclusion.

Concerning the safety of IRE, There was only one available observational study to IRE, and it reported only on acute toxicity and found grade 1 GU toxicity among 24% of patients and grade 2 GU toxicity among 11% of patients. PT and SBRT showed similar frequencies of toxicity - GU toxicity grade 1 occurred in around half of the patients and GI toxicity in around one-third of the patients. Grade 2 GU acute toxicity occurred in approximately one-quarter of PT-treated patients and about 18% of SBRT-treated patients. However, the authors declare that the quality of evidence ranges from very low to low and thus couldn’t make a proper conclusion.

To conclude, there is inadequate and insufficient evidence to show that IRE, SBRT and PT have either a positive impact on survival and quality of life or the ability to prevent or delay prostatectomy. There are 39 studies currently running and the authors hope that these could bring better evidence.

See the full report in German (with summary in English) here.

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