New Study Shows Early Radioligand Therapy Can Delay Prostate Cancer Progression


Add-On Radioligand Therapy Slows Metastatic Hormone-Sensitive Prostate Cancer | MedPage Today

Important trial results for men with newly diagnosed metastatic prostate cancer—what you need to know

Men with metastatic hormone-sensitive prostate cancer just received promising news from a major international study. The PSMAddition trial, presented at the European Society for Medical Oncology (ESMO) Congress in Berlin on October 21, 2025, showed that adding a targeted radioactive treatment called lutetium-177-PSMA-617 (brand name Pluvicto) to standard hormone therapy significantly delayed disease progression.

Understanding the Study

The trial included 1,144 men with newly diagnosed or minimally treated metastatic hormone-sensitive prostate cancer from 20 countries. All participants received the current standard treatment: androgen deprivation therapy (ADT) combined with an androgen receptor pathway inhibitor (ARPI). Half of the men also received the radioligand therapy.

What Are the Results?

The good news: After nearly two years of follow-up, men who received the radioligand therapy had a 28% lower risk of their cancer progressing or causing death compared to those who received standard treatment alone.

More specifically:

  • Disease progression occurred in about 20% of men who received radioligand therapy versus 27% in the standard treatment group
  • Complete tumor responses were much more common with the radioligand—57% versus 42%
  • PSA levels dropped significantly more with the radioligand therapy

The challenging news: The study hasn't yet shown that this treatment helps men live longer overall, and it comes with more side effects than standard treatment alone.

What Is Lutetium-PSMA Therapy and How Does It Work?

Think of this treatment as a "smart missile" for cancer cells. Here's how it works in simple terms:

Most prostate cancer cells produce large amounts of a protein called PSMA (prostate-specific membrane antigen) on their surface—like a special marker that identifies them as cancer. The treatment combines two parts: a targeting molecule (PSMA-617) that finds and attaches to these cancer cells, and a radioactive element (lutetium-177) that delivers radiation directly to destroy them.

Once injected into your bloodstream through an IV, the medicine travels throughout your body, finds cancer cells wherever they are, attaches to them, and delivers targeted radiation that damages the cancer cell's DNA, ultimately killing it—while causing minimal harm to healthy tissues.

Before you can receive this treatment, you need a special PSMA PET scan to confirm your cancer cells have enough PSMA for the treatment to work effectively. More than 80% of prostate cancer patients have cancer that expresses high levels of PSMA.

What to Expect During Treatment

If you're considering this therapy, here's what the treatment process involves:

The Procedure:

  • Treatment takes place in a hospital's nuclear medicine department, where a healthcare professional injects the medicine into a vein in your arm
  • The injection itself only takes a few minutes, followed by a brief observation period of one to two hours
  • Most people receive treatment cycles every 6 weeks, typically for a total of six treatments
  • You can go home the same day, but you'll need to follow safety precautions for a few days regarding close contact with others, especially pregnant women and children

Monitoring: Blood tests are done before each treatment cycle to monitor your kidney, liver, and bone marrow function.

Side Effects: What You Should Know

In the PSMAddition trial, treatment-related side effects occurred in about 89% of patients receiving radioligand therapy compared to 70% with standard treatment alone. However, most side effects were manageable:

Most Common Side Effects:

  • Dry mouth (47% of patients)—this happens because salivary glands naturally have some PSMA
  • Low blood cell counts (44%)
  • Fatigue and nausea
  • Dry eyes (less common)

More serious side effects (grade 3 or higher) occurred in about 23% of patients receiving radioligand therapy versus 12% with standard treatment. Important to note: no deaths were attributed to the treatment in either group.

Most symptoms improve within a few days after treatment, though dry mouth and dry eyes can occasionally be permanent.

The Expert Debate

While the lead researcher, Dr. Scott Tagawa from Weill Cornell Medicine, concluded the findings support using radioligand therapy early in treatment, not all experts agree it's ready for widespread use.

Dr. Arun Azad from Peter MacCallum Cancer Centre in Australia raised important concerns: the treatment hasn't been shown to help patients live longer, and there are quality of life impacts from the side effects. He suggested the treatment might be most appropriate for men with particularly aggressive disease, such as high-volume cancer or very high PSMA levels on scans, rather than for everyone with newly metastatic prostate cancer.

Other experts point out that not all patients may need the full six treatment cycles—some may achieve excellent responses with fewer treatments, which could reduce side effects.

Why Didn't the Study Show a Survival Benefit?

One important factor: 16% of men in the standard treatment group were allowed to switch to radioligand therapy when their cancer progressed, which may have reduced any survival advantage in the experimental group. With longer follow-up and more data, a survival benefit may yet emerge.

What Does This Mean for You?

Current FDA Status: Lutetium-177-PSMA-617 (Pluvicto) is currently FDA-approved for men with metastatic castration-resistant prostate cancer—a more advanced stage than the patients in this study. Novartis, the drug manufacturer, plans to seek FDA approval for use in hormone-sensitive disease in the second half of 2025.

Questions to Discuss with Your Doctor:

  1. Am I a good candidate? Ask about your PSMA PET scan results and disease characteristics
  2. What are my disease volume and aggressiveness? This might help determine if you're someone who would benefit most
  3. How do the benefits compare to the side effects in my specific situation?
  4. What other treatment options should we consider?
  5. What's the timeline for potential FDA approval for earlier-stage disease?

The Bigger Picture

This study represents a paradigm shift—historically, radioligand therapies were reserved for late-stage, castration-resistant disease when options were limited. PSMAddition demonstrates that using this targeted treatment earlier may enhance responses and delay progression to castration-resistant disease.

Multiple other clinical trials are now exploring radioligand therapy in different prostate cancer settings, including studies called SPLASH, ECLIPSE, ARROW, and LUNAR, as well as research into next-generation treatments using different radioactive elements like actinium-225.

Bottom Line

The PSMAddition trial shows that adding radioligand therapy to hormone treatment can meaningfully delay cancer progression in men with newly metastatic prostate cancer. However, it comes with trade-offs: more side effects and no proven survival benefit yet. The treatment may be most beneficial for men with high-risk, aggressive disease characteristics.

This is an evolving story, and what matters most is having an individualized discussion with your oncology team about your specific situation, disease characteristics, personal priorities, and the balance between delaying progression and managing side effects.

Sources

  1. Bankhead, C. (2025, October 21). Add-On Radioligand Therapy Slows Metastatic Hormone-Sensitive Prostate Cancer. MedPage Today. https://www.medpagetoday.com

  2. Sayyid, R.K. (2025, October 21). ESMO 2025: Discussant – Phase III Trial of [177Lu]Lu-PSMA-617 Combined with ADT + ARPI in Patients with PSMA-Positive Metastatic Hormone-Sensitive Prostate Cancer (PSMAddition). UroToday. https://www.urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164134-esmo-2025-discussant-phase-iii-trial-of-177lu-lu-psma-617-combined-with-adt-arpi-in-patients-with-psma-positive-metastatic-hormone-sensitive-prostate-cancer-psmaddition.html

  3. Novartis. (2025, October 19). PSMAddition data show Novartis Pluvicto™ delays progression to end-stage prostate cancer [Press release]. https://www.novartis.com/news/media-releases/psmaddition-data-show-novartis-pluvictotm-delays-progression-end-stage-prostate-cancer

  4. Despite Positive Data From the PSMAddition Trial, Expert at ESMO 2025 Raises Concerns. (2025, October 21). Oncology News Central. https://www.oncologynewscentral.com/prostate-cancer/despite-positive-data-expert-raises-concerns-over-prostate-cancer-treatment

  5. GlobeNewswire. (2025, October 19). PSMAddition data show Novartis Pluvicto™ delays progression to end-stage prostate cancer. https://www.globenewswire.com/news-release/2025/10/19/3169022/0/en/PSMAddition-data-show-Novartis-Pluvicto-delays-progression-to-end-stage-prostate-cancer.html

  6. Chavarriaga, J. (2025, October 21). ESMO 2025: What Is next After Clinical Trials Testing PSMA & Lutetium-177? UroToday. https://www.urotoday.com/conference-highlights/esmo-2025/esmo-2025-prostate-cancer/164084-esmo-2025-what-is-next-after-clinical-trials-testing-psma-amp-lutetium-177.html

  7. Lutetium Lu 177 Vipivotide Tetraxetan Plus ARPI/ADT Yields Superior PFS in PSMA+ mHSPC. (2025, October 19). OncLive. https://www.onclive.com/view/lutetium-lu-177-vipivotide-tetraxetan-plus-arpi-adt-yields-superior-pfs-in-psma-mhspc

  8. PSMAddition: ¹⁷⁷Lu-PSMA-617 Extends PFS in mHSPC. (2025, October 19). OncoDaily. https://oncodaily.com/oncolibrary/psmaddition-%C2%B9%E2%81%B7%E2%81%B7lu-psma-617-mhspc

  9. Morris, M.J., Castellano, D., Herrmann, K., et al. (2025). Final overall survival and safety analyses of the phase III PSMAfore trial of [177Lu]Lu-PSMA-617 versus change of androgen receptor pathway inhibitor in taxane-naive patients with metastatic castration-resistant prostate cancer. Annals of Oncology. https://www.annalsofoncology.org/article/S0923-7534(25)00852-X/fulltext

  10. Adding lutetium (177Lu) vipivotide tetraxetan to SOC improves rPFS in mHSPC. (2025, October 14). Urology Times. https://www.urologytimes.com/view/adding-lutetium-177lu-vipivotide-tetraxetan-to-soc-improves-rpfs-in-mhspc

  11. University of Chicago Medicine. Lutetium-177 PSMA Therapy for Prostate Cancer (Pluvicto). https://www.uchicagomedicine.org/cancer/types-treatments/prostate-cancer/treatment/lutetium-177-psma-therapy-for-prostate-cancer

  12. PSMA: How It Can Help Treat Prostate Cancer. (2025, May 10). WebMD. https://www.webmd.com/prostate-cancer/prostate-cancer-treat-psma

  13. Sheba Medical Center. (2025, July 28). Lutetium-177 PSMA Therapy. https://www.shebaonline.org/treatment/lutetium-177-psma-therapy/

  14. Cleveland Clinic. (2025, June 30). PSMA-Targeted Therapy: Purpose & Results. https://my.clevelandclinic.org/health/treatments/24775-psma-targeted-therapy

  15. Tagawa, S.T., Sartor, O., Piulats, J.M., et al. (2025, October 21). Phase III trial of [177Lu]Lu-PSMA-617 combined with ADT + ARPI in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (PSMAddition). Presented at: 2025 ESMO Congress; Berlin, Germany. Abstract LBA6.

  16. ClinicalTrials.gov. NCT04720157. An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination with SoC, Versus SoC Alone, in Adult Male Patients with mHSPC (PSMAddition). https://clinicaltrials.gov/study/NCT04720157

 

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