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Practical considerations for prostate hypofractionation in the developing world

Nature Reviews Urology volume 18, pages 669–685 (2021)Cite this article

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Abstract

External beam radiotherapy is an effective curative treatment option for localized prostate cancer, the most common cancer in men worldwide. However, conventionally fractionated courses of curative external beam radiotherapy are usually 8–9 weeks long, resulting in a substantial burden to patients and the health-care system. This problem is exacerbated in low-income and middle-income countries where health-care resources might be scarce and patient funds limited. Trials have shown a clinical equipoise between hypofractionated schedules of radiotherapy and conventionally fractionated treatments, with the advantage of drastically shortening treatment durations with the use of hypofractionation. The hypofractionated schedules are supported by modern consensus guidelines for implementation in clinical practice. Furthermore, several economic evaluations have shown improved cost effectiveness of hypofractionated therapy compared with conventional schedules. However, these techniques demand complex infrastructure and advanced personnel training. Thus, a number of practical considerations must be borne in mind when implementing hypofractionation in low-income and middle-income countries, but the potential gain in the treatment of this patient population is substantial.

Key points

  • The global burden of prostate cancer is increasing and prostate cancer is becoming a major source of health-care burden in low-income and middle-income countries (LMICs).

  • Radiotherapy is an essential treatment modality in the management of prostate cancer. However, radiotherapy resources are lacking in LMICs, resulting in excess morbidity and mortality.

  • Hypofractionated radiotherapy schedules offer an opportunity to maintain excellent treatment outcomes while shortening curative radiotherapy courses. This approach expands the treatment capacity and could improve crucial access in communities with limited radiotherapy resources.

  • Initial investments are required for technological upgrades, such as intensity-modulated radiotherapy and image-guided radiotherapy, as well as in specialized training in order to optimally provide hypofractionated treatment. Discussion amongst government agencies and device manufacturers is essential to lower these costs.

  • Personnel training and access to external consultation are critical resources for developing radiotherapy centres. Information and communication technologies enable remote guidance between developing and developed radiotherapy centres.

  • In the long term, hypofractionation programmes result in long-term cost savings and simultaneously expand patient access to a curative modality in the management of prostate cancer.

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Fig. 1: Isodose map of moderate hypofractionation plans.
Fig. 2: Cumulative dose volume histograms (DVH) for moderate hypofractionation. Cumulative DVHs for the planning target volume (red) and rectum (brown) for the 3D treatment plan (triangle) and IMRT (square) plans from Fig. 1 are depicted.
Fig. 3: Isodose map of ultrahypofractionation plans.
Fig. 4: Cumulative dose volume histograms (DVH) for ultrahypofractionation. Cumulative DVHs for the planning target volume (red) and rectum (brown) for the non-image-guided radiotherapy (triangle) and image-guided radiotherapy (square) plans from Fig. 3.

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Authors and Affiliations

  1. Division of Radiation Oncology, Cancer Centre of Southeastern Ontario, Queen’s University, Kingston, Canada

    Michael Yan, Nikitha Moideen & Fabio Y. Moraes

  2. Department of Radiation Oncology, Americas Centro de Oncologia Integrado, Rio de Janeiro, Brazil

    Andre G. Gouveia

  3. Department of Radiation Oncology, Cedars Cancer Centre, McGill University, Montreal, Canada

    Fabio L. Cury

  4. Queen’s University School of Medicine, Department of Public Health Sciences, Kingston, Canada

    Vanessa F. Bratti

  5. Department of Medical Physics, Cedars Cancer Centre, McGill University, Montreal, Canada

    Horacio Patrocinio

  6. Radiation Medicine Program, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada

    Alejandro Berlin

  7. Department of Radiation Oncology, London Regional Cancer Program, Western University, London, Canada

    Lucas C. Mendez

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Contributions

M.Y., A.G.G., N.M., V.F.B., L.C.M. and F.Y.M. researched data for the article. A.G.G., F.L.C., L.C.M. and F.Y.M. made substantial contributions to discussions of content. M.Y., A.G.G., F.L.C., N.M., V.F.B., H.P., A.B. and F.Y.M. wrote the article. All authors reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Fabio Y. Moraes.

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Competing interests

H.P. declares consulting fees and conference support from Varian Medica Systems unrelated to the current work. F.L.C. declares grants from Boston Scientific and Sanofi, honoraria and conference support from Varian Medical Systems and participates on the data safety monitoring board of Abbvie and Bayer. The other authors declare no competing interests.

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Nature Reviews Urology thanks S. Arcangeli, F. Alongi and the other, anonymous, reviewers for their contribution to the peer review of this work.

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Related links

AFRONET: https://www.iaea.org/resources/webinar/africa-radiation-oncology-network-afronet

BOTSOGO: http://www.botsogo.org/

Global RT: http://globalrt.org/

Radiating Hope: https://www.radiatinghope.org/

Glossary

Alpha/beta ratio

The ratio of linear and quadratic components that make up the model of cancer cell killing in response to radiotherapy; a measure of intrinsic sensitivity of a cell to radiation-induced death.

Cone-beam CT

(CBCT). A medical imaging technique utilizing divergent X-ray beams to perform CT. Often used for onboard image-guided radiotherapy.

Co-registered

Within treatment planning systems, the fusion or overlay of two separate images, often of different modalities (for example, MRI and CT) to aid treatment planning.

Soft-tissue matching

During image-guided radiotherapy, matching is performed before each treatment fraction to ensure treatment accuracy. In prostate radiotherapy using CBCT, the soft tissue interface between the rectum and prostate (as opposed to bony landmarks) are used for set-up verification.

Dose constraint points

Accepted dosimetric values to ensure the safety of normal tissues. Often, these constraints are expressed as a maximal dose limit to a specified volume of a normal tissue.

Megavoltage photons

Megavoltage is the most common energy level used in modern linear accelerators for the treatment of most cancers owing to its deep penetration. Other photon energies, such as kilovoltage or orthovoltage, can be used for superficial cancers such as skin cancers.

Incremental cost-effectiveness ratio

(ICER). A summary measure representing the economic value of an intervention in comparison to an alternative (comparator). The ICER is usually expressed as a monetary amount per quality-adjusted life year.

Quality-adjusted life year

(QALY). A measure of disease burden that accounts for the quality and quantity of life lived. QALY scores range from 1 (a year lived in perfect health) to 0 (death). Comorbid conditions will result in a QALY measure that is intermediate to these values.

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Yan, M., Gouveia, A.G., Cury, F.L. et al. Practical considerations for prostate hypofractionation in the developing world. Nat Rev Urol 18, 669–685 (2021). https://doi.org/10.1038/s41585-021-00498-6

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