Dr. Hoffe first reviewed the mechanisms of radiation-induced toxicity. Radiation induces radical production and oxidative stress that damages the vasculature within the irradiated field. This leads with time to the radiation fibrosis syndrome, which manifests in three phases.
Pelvic radiotherapy impacts fertility and childbearing, and early consultation to navigate these issues is suggested, especially if cryopreservation is possible. In some cases, it may be possible to move the ovaries outside of the radiation field, but patients should also be aware that a uterus that has received radiation will not be able to carry a fetus to term. Vaginal morbidity with radiation (external beam and/or brachytherapy) is another consideration. The prevalence of grade 1 and 2 toxicity increases over the first two years post-therapy and then plateaus, with a relatively low rate of grade 3 and 4 morbidity – approximately 2% in one study. The risk of any grade 1 or higher vaginal stenosis in that same study was over 75%. Interventions such as vaginal dilation once the mucosa is healed (typically a month later) can successfully reverse stenosis in the majority of cases. The ongoing randomized DILANA trial is assessing whether dilation during treatment is another option for limiting stenosis. For women who lose ovarian function, discussions around hormonal therapy and lubricants are an essential part of the survivorship conversation.
Men can also experience significant late effects from pelvic radiation due to damage to vessels, the neurovascular bundle as well as penile tissue. This can result in erectile dysfunction, ejaculatory issues, or low testosterone. A number of strategies are available to ameliorate these effects including medications (Sildenafil and tadalafil are effective in > 50% of patients), penile implants, vacuum erection devices, psychosexual therapy, and testosterone replacement depending on the context. A recent phase two study examined the efficacy of an MR-angiogram-based RT planning strategy in prostate cancer by contouring around the internal pudendal artery and corpus cavernosum.1 Long term effect data from this approach is still pending.
Various alternative radiation modalities are being trialed in different contexts in an attempt to limit treatment toxicity. Proton therapy appears to result in decreased GI tract toxicity across multiple disease types, including prostate cancer, but data on late effects are still emerging. Image-guided radiotherapy, wherein an image is taken daily and overlaid with the planning imaging, can also limit toxicity by allowing for variations in anatomic positioning due to differences in urine and stool amounts.
Radiation therapy is associated with a risk of secondary cancers. A meta-analysis published in 20162 suggested that after prostate external beam radiotherapy, the risk of bladder cancer ranges from 0.1% to 3.8%, the risk of colorectal cancer is 0.3% to 4.2%, and the incidence of rectal cancer is 0.3% to 1.2%. A rectal spacer may help spare the anterior rectal wall from higher doses of radiation. Treatment of these secondary cancers is more challenging but can be accomplished by techniques such as endorectal brachytherapy.
Urinary late effects are rare and vary with the irradiated site. Urethral strictures can occur after treatment of cervical and prostate cancer, whereas treatment of bladder and anal cancer can lead to hemorrhagic cystitis and bladder necrosis. Urinary morbidity is more likely in patients with prostatic hyperplasia who require radiation treatment for rectal cancer. One technique to limit this is to utilize prostatic artery embolization to shrink the prostate, improve baseline IPSS score, and limit the risk of urinary toxicity.
Dr. Hoffe then discussed the risks from radiation to bone and for peripheral arterial disease, summarized below.
Dr. Hoffe ended her talk by summarizing that modern radiation therapy has acute and late toxicity, the latter requiring individualized survivorship care. Ongoing prospective studies and research will hopefully optimize this survivorship care to limit morbidity to sexual, mental, and physical health.
Presented by: Sarah E. Hoffe, MD, section head of Gastrointestinal Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, Virtual Annual Meeting #ASCO21, June, 4-8, 2021
- Spratt D., Lee JY., Dess R. et al. "Vessel-sparing Radiotherapy for Localized Prostate Cancer to Preserve Erectile Function: A Single-arm Phase 2 Trial." European Urology. 2017. 72, 4, 617-624.
- Wallis C., Mahar A., Choo R. et al. "Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis." BMJ. 2016. 352:i851.