Finding Value for Protons: The Case of Prostate Cancer?,☆☆,

https://doi.org/10.1016/j.semradonc.2017.11.003Get rights and content

The standard radiotherapy treatment for prostate cancer is intensity-modulated radiotherapy (IMRT). An alternative option is proton beam therapy (PBT). PBT is a safe and effective treatment, but does it add value over IMRT? We explore this controversial question by examining the available dosimetric and clinical evidence.

Introduction

For men in the United States, prostate cancer is the most common malignancy.1 When the disease is localized, it can be cured by radiotherapy.2, 3 This treatment is typically intensity-modulated radiotherapy (IMRT)4—an external beam of photons sculpted to closely fit the target. These photons are massless, uncharged quanta of electromagnetic radiation. They pass completely through the patient and deliver dose along their entire path.

An alternative treatment is proton beam therapy (PBT). Unlike photons, protons are heavy, charged particles. PBT stops within the body and delivers virtually no dose past the target, thus reducing radiation exposure to normal tissues (Fig).5 PBT is a safe and effective treatment for prostate cancer6, 7, 8—but does it add value over IMRT? In the article that follows, we explore this controversial question.9, 10

Section snippets

Value: A Two-Part Equation

First, we must define value. A common formulation is health care outcomes divided by cost.11 This equation’s denominator poses a challenge for expensive technologies. For example, prostate PBT costs ~$13,000-14,000 more than IMRT,12, 13 although this gap may shrink with cheaper PBT equipment14 and shorter-course treatment.15

To provide value, PBT must therefore improve health outcomes relative to IMRT. This could mean either better cancer control or fewer side effects. It seems unlikely that PBT

Radiotherapy Side Effects: Scope of the Problem

The principal potential side effects from prostate radiotherapy are bladder, bowel, and erectile dysfunction. The precise frequency and magnitude of these toxicities is challenging to pinpoint,21 but we can reach some general conclusions: in the short term, radiotherapy causes moderate rates of transient urinary and rectal irritation; in the long run, it causes moderate rates of erectile dysfunction and a smaller risk of rectal complications.22, 23, 24, 25

One source of high-quality toxicity

Dosimetric Evidence

New radiotherapy technologies are often initially evaluated in silico. There are many of these dosimetric studies comparing PBT and IMRT for prostate cancer.34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45 The analyses are heterogeneous; they vary with respect to target volumes (prostate alone, prostate plus seminal vesicles, and prostate plus pelvic lymph nodes), planning uncertainty margins, delivered dose, beam arrangements, photon/proton delivery technique, and planning optimization strategy.

Claims-based Evidence: Pros and Cons

Claims-based analyses draw “information from a diverse array of patients, providers, and treatment facilities in real-world practice.”61 These studies can leverage the power of large numbers to detect even modest differences between IMRT and PBT. Yet, claims-based datasets also have notable weaknesses. For example, exposure misclassification (incorrectly identifying the type of radiotherapy a patient received) and outcome misclassification (incorrectly assuming that billing codes accurately

Patient-level Evidence: Pros and Cons

Patient-level analyses bring a wealth of granular data that are often missing from claims-based studies. For example, baseline comorbidities and details of treatment can help ensure that IMRT and PBT cohorts are reasonably similar. Toxicity can be directly measured by physician or patient report, rather than relying on surrogate billing claims. However, patient-level analyses also have limitations. They often examine fewer subjects, and therefore may fail to detect modest differences between

Summary and a Way Forward

Can PBT provide value in the case of prostate cancer? In our view, this question hinges on whether PBT can meaningfully reduce side effects compared to IMRT. To date, the available evidence leaves us in the state of equipoise.

Dosimetric studies suggest that the potential benefit of PBT depends on whether side effects are caused by low-to-intermediate doses (where PBT is better than IMRT) or by higher doses (where PBT might be the same, better, or worse than IMRT).

Clinical studies largely

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  • Cited by (3)

    • Proton therapy for prostate cancer: A review of the rationale, evidence, and current state

      2019, Urologic Oncology: Seminars and Original Investigations
      Citation Excerpt :

      Essential to understanding the controversy of PBT for prostate cancer, one must also appreciate the economics and practice patterns of these competing modalities. The value (healthcare outcomes divided by cost [62]) of PBT for prostate cancer has been questioned [63–67]. The adoption of expensive technologies with unproven benefit in radiation oncology has invited scrutiny to the specialty, and prostate cancer epitomizes this [68,69].

    Disclosures: Dr. Bekelman received support from grant K07-CA163616 from the National Cancer Institute and the Young Friends of the Abramson Cancer Center Fund. The contents of this paper do not represent the views of the United States Department of Veterans Affairs or the United States Government.

    ☆☆

    Conflicts of interest: none.

    Acknowledgements: We thank Maura Kirk, MS, from the Department of Radiation Oncology at the University of Pennsylvania, for assistance with the manuscript figure. Ms. Kirk was not compensated for her efforts.

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