As clinicians push radioligand therapy into earlier lines of prostate cancer treatment, Dr. Daniel Spratt, Chairman of Radiation Oncology at University Hospitals (UH) Seidman Cancer Center, explains the importance of working to optimize systemic therapy while preserving quality of life.
“When we believe a patient will benefit from a systemic treatment, we need to decide what’s going to provide at least equal efficacy with the best quality of life,” Dr. Spratt explains. “Right now, radioligand therapy — specifically PSMA lutetium — probably has a more favorable toxicity profile or quality-of-life profile than both hormone therapy as well as chemotherapy.”
Currently, Dr. Spratt says, how long eligible patients live, whether they are given chemotherapy or radioligand therapy, is similar, but “the way the patients feel is markedly improved with the radioligand therapy.”
Patient-reported quality-of-life measures consistently favor radioligands, even when patients receive up to six cycles of treatment.
Understanding Radioligand Toxicities
Because radioligand toxicities vary by target and payload, routine monitoring is critical with lutetium-PSMA-617, Spratt says.
“The main toxicities people are looking out for are bone marrow suppression — monitoring blood counts — dry mouth, some GI symptoms like nausea or loose stools, fatigue, but overall, depending on how many cycles you give, it’s fairly well tolerated,” he says.
Still, full physician oversight is key. “Before every dose, patients definitely should be seeing a physician to evaluate them,” Spratt explains.
Potential Long-Term Radiation Effects
While chemotherapy toxicities are well characterized after decades of use, radioligands introduce a different kind of uncertainty: whole-body radiation exposure.
“One of the concerns moving it earlier is that you are giving radiation through the whole body,” Spratt says. “Could this type of radiation cause cancer 10, 15, 20 years later?”
Radioligands are excreted through the urinary system and some dose is given to the kidneys, Spratt says, noting the long-term effects will need to be further studied.
Since the field simply does not yet have decades-long follow-up for patients treated earlier in the disease course, that uncertainty is driving a strong emphasis on dosing strategy.
Why Dose Matters — Especially Earlier
“One of the benefits in earlier stages of disease is that you can often give fewer doses,” Spratt says. In advanced disease, patients may receive six cycles of radioligand therapy. Earlier in the disease course, two or three cycles may be sufficient.
“If you give too much dose early, you might see side effects manifest years later,” he cautioned. “That’s why if you’re using it earlier, we really need to be using it as just two or three doses — not six or more — and closely monitoring patients over time.”
This dosing flexibility may ultimately allow clinicians to preserve radioligand therapy’s quality-of-life advantage while minimizing long-term risk.
Looking To The Future
The comparison between radioligands and chemotherapy is reshaping how clinicians discuss tradeoffs with patients. Rather than choosing between efficacy and tolerability, the conversation is increasingly about achieving similar disease control while optimizing how patients feel during treatment — and potentially after it.
Radioligand therapy is not without unanswered questions. But as Spratt notes, its favorable toxicity profile and dramatic quality-of-life advantages are already influencing how systemic therapy choices are made — especially as treatment moves earlier in prostate cancer care.
For now, the challenge is balance — leveraging the benefits of radioligands while remaining vigilant about what time has not yet revealed.
NOTE: Early radioligand therapy, either in localized high risk prostate cancer or mCRPC that has not yet failed ARPI, is not currently an approved use by the FDA and should only be administered within the context of a clinical trial to eligible patients.
