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“Give me five” ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach

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Abstract

Ultra-hypofractionated radiotherapy (RT) is given over a shorter time with larger doses with respect to conventional fractionation in patients with localized prostate cancer (PCa). The use of hypofractionation is supported both from the radiobiological point of view (the low α/β-ratio in PCa and dose escalation) and from the rising number of clinical evidences. The aim of this study is to review our data regarding oncological outcomes, namely biochemical progression-free survival (b-PFS) and clinical progression-free survival (c-PFS), acute and long-term toxicities in patients treated with a ultra-hypofractionated RT. A series of 194 patients with clinically localized PCa treated primarily with ultra-hypofractionated RT using image-guided intensity modulated RT (IG-IMRT) at our Institute from 2012 to 2015 was included in this analysis. According to NCCN risk group classification, 65 (33.5%) patients were low risk, 101 (52.1%) intermediate risk, and 28 (14.4%) high risk. Androgen deprivation therapy (ADT) was given to 61 patients (31.4%). A 169 patients (87.1%) received 35 Gy in 5 fractions, while 25 patients (13%) received 32.5 Gy in 5 fractions (usually given in patients with comorbidity). The median duration of the treatment was 10 days (IQR 9–12). Biochemical relapse was defined as a rise of prostate specific antigen (PSA) > 2 ng/ml above nadir. b-PFS, c-PFS, and freedom from gastro-intestinal (GI) and genito-urinary (GU) toxicity curves were calculated by the Kaplan–Meier method. Log-rank test and multivariate Cox models were used to investigate the role RT dose and heterogeneity by NCCN risk groups adjusting for prognostic factors. Data on acute and late term toxicities were collected according to RTOG/EORTC grading system. With a median follow-up of 30 months, 17 patients experienced PSA failure (9%). The 3-year b-PFS was 87% for all patients and rates stratified for the NCCN risk were 94, 82, and 66% for low-, intermediate-, and high-risk groups, respectively. Log-rank tests indicate that biochemical progression was significantly greater for patients with initial PSA (iPSA) greater than 7 ng/ml (P = 0.04), high- and intermediate-risk groups (P = 0.002), low total dose (P = 0.02) and Gleason score (GS) equal or greater than 7 (P = 0.04). No statistically significant association was found with T stage nor ADT. In multivariate analyses, total dose (P = 0.03) and risk groups (P = 0.03) remained significantly associated with recurrence. Acute and late GI and GU toxicity were acceptable. The toxicity of ultra-hypofractionated IG-IMRT in a large clinical cohort of PCa patients was tolerable and confirmed that this treatment is safe and offers excellent tumor control. Moreover, the hypofractionated RT allows to deliver the whole RT over 10 days with a sensible impact in patients’ quality of life and potential overall health system and social benefits.

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Acknowledgements

This work was partially supported by the research grants from the Associazione Italiana per la Ricerca sul Cancro (AIRC): IG-13218 “Short-term high precision RT for early prostate cancer with concomitant boost to the dominant lesion,” registered at ClinicalTrials.gov NCT01913717, approved by IEO S768/113 and IG-14300 “Carbon ions boost followed by pelvic photon radiotherapy for high risk prostate cancer,” The Sponsor did not play any role in the study design, collection, analysis and interpretation of data, nor in the writing of the manuscript, nor in the decision to submit the manuscript for publication.

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Author notes

  1. Sarah Pia Colangione

    Present address: Radiotherapy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

  2. Giorgia Timon

    Present address: Radiation Therapy Unit, Department of Oncology and Advanced Technology, Azienda Ospedaliera Arcispedale S Maria Nuova, Istituto di Ricovero e Cura a Carattere Scientifico, Reggio Emilia, Italy

Authors and Affiliations

  1. Department of Radiotherapy, European Institute of Oncology, Via Ripamonti 435, 20141, Milan, Italy

    Giulia Marvaso, Giulia Riva, Delia Ciardo, Cristiana Fodor, Dario Zerini, Sarah Pia Colangione, Giorgia Timon & Barbara A. Jereczek-Fossa

  2. Department of Oncology and Hemato-oncology, University of Milan, Milan, Italy

    Giulia Riva & Barbara A. Jereczek-Fossa

  3. Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

    Sara Gandini

  4. Unit of Medical Physics, European Institute of Oncology, Milan, Italy

    Stefania Comi, Raffaella Cambria & Federica Cattani

  5. Department of Urology, European Institute of Oncology, Milan, Italy

    Ottavio De Cobelli

  6. University of Milan, Milan, Italy

    Ottavio De Cobelli

  7. Scientific Directorate, European Institute of Oncology, Milan, Italy

    Roberto Orecchia

  8. Department of Medical Imaging and Radiation Sciences, European Institute of Oncology, Milan, Italy

    Roberto Orecchia

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  1. Giulia Marvaso
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Correspondence to Delia Ciardo.

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The authors declare no potential conflicts of interest.

Ethical approval

In this research, no animals were involved. All patients signed a written informed consent for stereotactic body radiation therapy (SBRT) and written informed consent for the use of the anonymized data for research or educational purpose. The study was performed within the Institutional Ethics Committee notification regarding clinical and dosimetric aspects of hypofractionated image-guided RT (IGRT) for PCa (CE notification n. 79).

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Marvaso, G., Riva, G., Ciardo, D. et al. “Give me five” ultra-hypofractionated radiotherapy for localized prostate cancer: non-invasive ablative approach. Med Oncol 35, 96 (2018). https://doi.org/10.1007/s12032-018-1155-y

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