expert roundtables

Understanding the Risks of Radiation Therapy and Frequent Imaging

by Peter R. Carroll, MD, MPH; and Michael J. Morris, MD

Overview

Radiation therapy and diagnostic imaging each have fundamental applications in the approach to prostate cancer. Weighing the risks and benefits of exposure to ionizing radiation helps to ensure that a favorable balance is achieved for each patient, at each phase of the disease.

Q:

How do you counsel patients about the risks of radiation therapy and frequent imaging?

Michael J. Morris, MD

Prostate Cancer Section Head, Division of Solid Tumor Oncology
Memorial Sloan Kettering Cancer Center
New York, NY

A patient who is expected to have severe or fatal consequences from their prostate cancer is more likely to accept the risks from an imaging study that might furnish useful insight into the distribution, growth rate, or biology of their disease. It is a question of risk and benefit.”

Michael J. Morris, MD

When deciding whether a patient should undergo therapeutic or diagnostic radiation, we need to weigh the risks of radiation against the risk of their disease. A patient who faces a nominal risk from their disease may not consider any treatment, whether radiation therapy or otherwise, and may not require imaging. On the other hand, a patient who is expected to have severe or fatal consequences from their prostate cancer is more likely to consider treatment, including those that involve radiation, and is more likely to accept the risks from an imaging study that might furnish useful insight into the distribution, growth rate, or biology of their disease. It is a question of risk and benefit. An experienced clinician can provide a realistic view to the patient on the risk from their disease compared with the risk associated with radiation therapy or diagnostic imaging. The patient can then decide if that risk outweighs the risk presented by the treatment or the diagnostic study itself.

With advancements in imaging, we are beginning to see a trend toward more frequent imaging. In the past, we would not order a computed tomography (CT) scan or a bone scan in somebody who had a prostate-specific antigen (PSA) level that was in the decimal range because we would not expect to see any clinically significant findings. However, with prostate-specific membrane antigen (PSMA)–based positron emission tomography (PET)/CT imaging, we can now detect disease even with very low PSA values. While PSMA imaging may lead to an increase in diagnostic imaging, we need more data demonstrating whether such early disease detection improves patient outcomes and how these imaging tools should best be put to use. For men with localized disease, the management of high-risk disease may well be benefitted by pretreatment PSMA staging studies. On the other hand, it is unclear whether men with low-risk disease would benefit from such new techniques, and, indeed, whether such men should be imaged at all. For patients with biochemical relapse after definitive local therapy, imaging at low PSA values can guide the choice of treatments. Focal salvage treatments can be curative if disease is detected in the bed, and men with distant disease might be spared unnecessary salvage treatment, in favor of systemic treatments. Clinical trials to better define these treatment paradigms are underway, so that we know who should be imaged and how these data can be used to their best effect in treating a patient’s disease.

Peter R. Carroll, MD, MPH

Ken and Donna Derr – Chevron Distinguished Professor
Taube Family Distinguished Professor in Urology
Department of Urology
UCSF – Helen Diller Comprehensive Cancer Center
University of California, San Francisco
San Francisco, CA

“I have seen an unnecessary utilization of diagnostic imaging in men with low-risk cancers (and in many with favorable intermediate-risk disease), despite guidelines that advise against bone and CT scans for men with low-risk disease. In patients with a PSA of less than 10 ng/mL and T1 or T2 disease, there is a minimal benefit with advanced imaging searching for metastatic disease unless it could help with treatment planning.”

Peter R. Carroll, MD, MPH

When I counsel patients on therapeutic radiation, I explain that, while there are some potential risks associated with radiation, the risk of a significant radiation-induced injury is relatively low. Although there is a risk of developing secondary malignancies, the risk remains low based on registry data and the literature. Moreover, long-term effects on bladder function and hematuria after radiation alone or radiation after surgery are generally manageable. I have seen an unnecessary utilization of diagnostic imaging in men with low-risk cancers (and in many with favorable intermediate-risk disease), despite guidelines that advise against bone and CT scans for men with low-risk disease. In patients with a PSA of less than 10 ng/mL and T1 or T2 disease, there is a minimal benefit with advanced imaging searching for metastatic disease unless it could help with treatment planning.

We also see an increased utilization in patients who have a rising PSA level after treatment, even though the PSA level is low. In my experience, a bone scan or a CT scan in a hormone-naïve patient with biochemical failure with a low PSA will not yield any informative results. However, with PSMA PET/CT, nearly half of the patients imaged may yield results. We need to gain a better understanding of when to consider PSMA PET/CT or magnetic resonance imaging. For patients with biochemical failure, we know that higher PSA levels will produce better yields, so I think that we should avoid imaging too early and wait until the PSA rises to a level where the sensitivity of PET is reasonable.

We also evaluate the primary tumor to determine whether advanced imaging is needed. For example, a patient with stage T3b prostate cancer with a negative margin is different than a patient with stage T2 prostate cancer and a positive margin. At my institution, the local failure rate on PSMA-based imaging in those who were treated with surgery was only 15%. In our series of patients with biochemical failure who were most likely to have regional or retroperitoneal node involvement, approximately one-fourth had visceral or bone disease. Therefore, we base our approach on the clinical pathologic features of the disease, the time to biochemical relapse, and PSA kinetics, which predict a positive response to radiation therapy.

References

Dutta SW, Alonso CE, Libby B, Showalter TN. Prostate cancer high dose-rate brachytherapy: review of evidence and current perspectives. Expert Rev Med Devices. 2018;15(1):71-79. doi:10.1080/17434440.2018.1419058

Eberhardt SC, Shah SK. R-SCAN: appropriate imaging for low-risk prostate cancer. J Am Coll Radiol. 2017;14(6):790-792. doi:10.1016/j.jacr.2017.01.041

Fendler WP, Calais J, Eiber M, et al. Assessment of 68Ga-PSMA-11 PET accuracy in localizing recurrent prostate cancer: a prospective single-arm clinical trial. JAMA Oncol. 2019;5(6):856-863. doi:10.1001/jamaoncol.2019.0096

Hoffman KE, Penson DF, Zhao Z, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. JAMA. 2020;323(2):149-163. doi:10.1001/jama.2019.20675

Moreira DM, Cooperberg MR, Howard LE, et al. Predicting bone scan positivity after biochemical recurrence following radical prostatectomy in both hormone-naive men and patients receiving androgen-deprivation therapy: results from the SEARCH database. Prostate Cancer Prostatic Dis. 2014;17(1):91-96. doi:10.1038/pcan.2013.59

Nguyen PL, Haddad Z, Ross AE, et al. Ability of a genomic classifier to predict metastasis and prostate cancer-specific mortality after radiation or surgery based on needle biopsy specimens. Eur Urol. 2017;72(5):845‐852. doi:10.1016/j.eururo.2017.05.009

Shevach J, Weiner A, Morgans AK. Quality of life-focused decision-making for prostate cancer. Curr Urol Rep. 2019;20(10):57. doi:10.1007/s11934-019-0924-2

Trabulsi EJ, Rumble RB, Jadvar H, et al. Optimum imaging strategies for advanced prostate cancer: ASCO guideline. J Clin Oncol. 2020;38(17):1963-1996. doi:10.1200/JCO.19.02757

Tsang YM, Vignarajah D, Mcwilliam A, et al. A pilot study on dosimetric and radiomics analysis of urethral strictures following HDR brachytherapy as monotherapy for localized prostate cancer. Br J Radiol. 2020;93(1106):20190760. doi:10.1259/bjr.20190760

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