Modern techniques can deliver radiation with more precision, and researchers are continually seeking to optimize the therapeutic index. A session at the 2024 ASTRO Annual Meeting shed light on prostate cancer treatment intensification and its effects on quality of life (QOL).

 Following these proceedings, featured expert Oliver Sartor, MD, was interviewed by Conference Reporter Editor-in-Chief Tom Iarocci, MD. Dr Sartor’s clinical perspectives on these findings are presented here.

Radiotherapy is being administered with ever-improving QOL outcomes in patients with prostate cancer, simply because we have better toxicity profiles from the more modern techniques. We are also delivering radiation more precisely now than in the past, and that precision can translate into improvements in terms of acute and chronic toxicities.

One of the elements that may be important to consider is the spacer technology. If a patient is liable to develop rectal toxicity, then putting a little space between the prostate and the rectum may make sense. Spacer technologies gently move the prostate away from the rectum, diminishing the exposure to the rectum and the related toxicities that are associated with external beam radiation therapy. That, I think, is important.

There will always be a bit of a yin and yang with treatment intensification. When you intensify the radiotherapy, you will probably have better biochemical control; however, you will also be risking some urinary injury. And it is not only the acute findings of cystitis but also the chronic findings related to bleeding, which can be somewhat problematic. I think that we need to be very careful when considering our newer techniques; if we do not have long-term follow-up, we have to be cautious about their adoption. Right now, I do feel as though the prostate cancer field is improving broadly in terms of toxicities because of the better techniques that are available, but we still need to be cautious and counsel our patients on what can happen down the line. This component of patient education is an absolute necessity.

Long-term, patient-reported outcomes from the randomized PROFIT study were presented by Noelia Sanmamed, MD, PhD, at ASTRO 2024 during a scientific session on prostate cancer treatment intensification (abstract 182). Participants with intermediate-risk disease were randomized to receive 78 Gy in 39 fractions over 8 weeks (ie, conventional fractionation) or 60 Gy in 20 fractions over 4 weeks (ie, moderate hypofractionation). Researchers found no significant differences in urinary-, bowel-, or sexual health–related QOL between the arms, and the proportion of patients reporting a decrement in bowel function at 48 months was significantly lower in the hypofractionated arm. Patient satisfaction was similar between the arms. I think that newer techniques, particularly moderate hypofractionation, are perfectly appropriate as standards of care.

When one considers the toxicities from radiotherapy, I do think that there is a tendency to focus solely on dosimetry, but the truth is that radiation tolerance may vary from individual to individual. When you irradiate normal tissue, the responses are not always identical. Now, we do have obvious examples of individual genetic influences, such as xeroderma pigmentosum, where we have an extreme radiation sensitivity. However, it may be that normal tissue tolerance can be modulated by a variety of factors, not all of which are completely clear. There is a lot more that we need to learn, so I would like to remain just a bit agnostic regarding the view that dosimetry is the only important parameter in radiation-associated toxicity. Patient-specific variables, including underlying genetic alterations, could play an important role as well.

Lastly, it should be noted that QOL may be impacted by ADT, whether it is short- or long-term ADT. With short-term ADT, the impacts are much more reversible, whereas that is not always the case with longer-term ADT. For instance, you can treat a 78-year-old man with prostate cancer for 2 years, after which his testosterone may never recover. In fact, a substantial proportion of patients with prostate cancer never recover after longer-term ADT. Further, while 6 months of ADT is clearly a much more reversible scenario, it is still castration. We call it hormonal therapy, or ADT, but it is castration, which means that patients are generally not going to feel good and may experience hot flashes, sexual dysfunction, and problems related to fatigue. Although short-term castration is not pleasant, short-term is preferable over long-term if it is, in fact, appropriate to give the patient short-term ADT.