Stereotactic Ablative Radiotherapy, “Microbeam” Boost, “Overtreatment”, and “Limited Life Expectancy”: Flawed Terminology in an Increasingly Precise Field of Prostate Cancer

External beam radiotherapy (EBRT) is the single most effective and versatile treatment in the management of locoregional cancer. Unfortunately, despite the advances in the precision of delivery, increase in the dose per fraction and shortening of the number of treatments (e.g., ultra-hypofractionation), the terminology used to describe this modality have been anything but precise. For example, while prostate cancer (PC) may be the most common site treated definitively with stereotactic body radiotherapy (SBRT), some experts prefer to use the term Stereotactic Ablative Radiation Therapy (SABR) for such treatments ^1,2.  However, cure has been seen following EBRT for many years, without any evidence of “ablation”, term frequently used for unspecific destruction of tissue (e.g., heat, cold or radiofrequency). The term SBRT may be sufficient in the setting of PC. While conformal high dose of radiation is delivered to the entire prostate as part of the SBRT, resulting in the killing of malignant cells, not all tissue within the prostate are subjected to an ablative radiation dose, meant to “destroy”. For example, the intraprostatic urethra though subjected to radiation during the delivery of such radiation treatment is not “ablated”. Although these terms have historically been used interchangeably, and have been the topic of various debate, clarification may be needed. When treating a tumor only for example in the lung or liver, when an ablative RT dose is delivered for tumor control, SABR may be rightfully describing such RT delivery. However, in case such PC where a whole organ is treated, because not all tissues are to be ablated (intraprostatic urethra), SBRT may be sufficient.

The term “microbeam” radiation therapy (MRT) is increasingly being used to refer to a highly focused form of radiation used to target sites where one or more dominant intraprostatic lesions (DIL) in the prostate as identified by multiparametric magnetic resonance imaging (MRI) ³.  However, this term usually reserved for something that requires a microscope to be visible, and there is nothing “micro”, about treatment of a prostate DIL with SBRT ⁴.

“Overtreatment” and “Limited Life Expectancy” are two related terminologies that are often used when it comes to PC management. A recent article by Daskivich et al. epitomized the challenges with the use of these terms. They report that “overtreatment” (e.g., RT) is too common in men with a limited life expectancy (LE) and localized PC ⁵.  They justify this assertion by citing studies focused on estimating LE.  In fact, however, none of the papers they reference provide evidence-based guidance as to who should not be treated, and most were published after the patients included in their analysis had already been treated.  They also note that LE is considered as a triage factor in the NCCN guidelines.  However, these guidelines do not prescribe specific treatments solely based on LE. For example, per these guidelines’, patients with high-risk PC and LE of ≤5 years may be managed with observation, androgen depravation therapy (ADT), or RT ⁶. In addition, in fact all of us have a LE.  Thus, the term “overtreatment” is inappropriate in this context, as it implies that based on high level evidence, the administration of RT was somehow misguided.

Multiple phase III randomized controlled trials (RCTs) have shown an improvement in survival with the addition of RT to the treatment of PC in men despite advanced age  (median age 70 years) ⁷.

Because of the long survival after progression with systemic disease, survival after treatment should not be the sole consideration in men with PC. Quality of life (QoL) must also play a pivotal role in guiding treatment decisions.  Years of ongoing interventions, such as ADT, chemotherapy, and palliative care (e.g., opioids) for symptomatic metastases, can profoundly impact on QoL. Many of these patients could have been cured with as few as 4 to 5 RT treatment sessions (with low morbidity), had they been treated earlier in the course of their disease, and avoided or delayed spending their final 5 to 10 years of life receiving palliative treatments ¹.

While estimates of LE maybe a useful tool in estate planning, it should not be the sole guide for the treatment selection in PC. It may at best guide a discussion regarding PC screening between a patient and primary care physician but not whether RT is appropriate after PSA screening and prostate biopsy were performed. Suggesting that patient with LE should receive no treatment after undergoing screening and a biopsy raises ethical questions about the purposes of these procedures and who should decide the appropriateness of a treatment.

Abbreviations

ADT – androgen deprivation therapy

DIL – dominant intraprostatic lesions

DIL – dominant intraprostatic lesions

EBRT – external beam radiotherapy

LE – life expectancy

MRI – multiparametric magnetic resonance imaging

MRI multiparametric magnetic resonance imaging

MRT – “microbeam” radiation therapy

PC – prostate cancer

QoL – Quality of life

RCTs – randomized controlled trials

SBRT – stereotactic body radiotherapy

Statements

Consent for publication: As the corresponding author, I confirm that the manuscript has been read and approved for submission by all co-authors.

Conflict of interests: The authors declare no conflict of interest.

Funding Sources: None

References:

1. Jackson WC, Silva J, Hartman HE, et al. Stereotactic Body Radiation Therapy for Localized Prostate Cancer: A Systematic Review and Meta-Analysis of Over 6,000 Patients Treated On Prospective Studies. International journal of radiation oncology, biology, physics. 2019;104(4):778-789.
2. Ong WL, Cheung P, Chung H, et al. Two-fraction stereotactic ablative radiotherapy with simultaneous boost to MRI-defined dominant intra-prostatic lesion – Results from the 2SMART phase 2 trial. Radiother Oncol. 2023;181:109503.
3. Regan SN, Dykstra M, Yin H, et al. Microboost in Localized Prostate Cancer: Analysis of a Statewide Quality Consortium. Adv Radiat Oncol. 2024;9(11):101629.
4. Pickett B, Vigneault E, Kurhanewicz J, Verhey L, Roach M. Static field intensity modulation to treat a dominant intra-prostatic lesion to 90 Gy compared to seven field 3-dimensional radiotherapy. International journal of radiation oncology, biology, physics. 1999;44(4):921-929.
5. Daskivich TJ, Luu M, Heard J, Thomas IC, Leppert JT. Overtreatment of Prostate Cancer Among Men With Limited Longevity in the Active Surveillance Era. JAMA internal medicine. 2024.
6. Schaeffer EM, Srinivas S, Adra N, et al. NCCN Guidelines(R) Insights: Prostate Cancer, Version 3.2024. J Natl Compr Canc Netw. 2024;22(3):140-150.
7. Roach M, 3rd, Thomas K. Overview of randomized controlled treatment trials for clinically localized prostate cancer: implications for active surveillance and the United States preventative task force report on screening? Journal of the National Cancer Institute Monographs. 2012;2012(45):221-229.