PSMA PET/CT Transforms Salvage Radiation for Biochemical Recurrence

Paradigm Shift for Evaluating, Treating Biochemical Recurrence in Prostate Cancer | MedPage Today

New Long-Term Data Shows Promise

BLUF (Bottom Line Up Front): A landmark 5-year study from UCLA demonstrates that PSMA PET/CT imaging can revolutionize treatment for prostate cancer patients experiencing biochemical recurrence after surgery. Nearly three-quarters of patients remained metastasis-free at 5 years when salvage radiation therapy was guided by this advanced imaging, with an impressive 97% overall survival rate. This represents a paradigm shift from "one-size-fits-all" to precision-guided treatment, allowing doctors to see cancer at PSA levels as low as 0.4 ng/mL—far earlier than conventional imaging—and tailor radiation therapy accordingly.

A Game-Changing Approach to Rising PSA After Surgery

For the 20-40% of prostate cancer patients who experience rising PSA levels after radical prostatectomy, the question has always been: where is the cancer, and how should we treat it? Traditional CT and bone scans often can't detect disease when PSA is below 1 ng/mL, forcing doctors to use standardized radiation protocols based on statistical probability rather than actual visualization of the cancer.

PSMA PET/CT imaging has changed this equation. The technology detects a protein (prostate-specific membrane antigen) that appears on the surface of most prostate cancer cells, lighting up even small deposits of disease that conventional imaging misses.

What the UCLA Study Found

Researchers at UCLA reviewed outcomes for 113 patients who underwent PSMA PET/CT-guided salvage radiation therapy between 2016 and 2021. These were men experiencing their first biochemical recurrence, with a median PSA of just 0.4 ng/mL—a level at which conventional imaging is essentially blind.

The results, published in the Journal of the National Comprehensive Cancer Network, were striking:

• 73% remained metastasis-free at 5 years (median metastasis-free survival: 76.4 months)
• Overall survival was 97.1% after median follow-up of 5 years
• Median progression-free survival was 49.2 months
• Half of patients (50.4%) experienced disease progression, but the imaging allowed early detection and intervention

Importantly, the study revealed optimal treatment strategies based on what PSMA PET/CT detected:

• For patients with no visible disease or trace disease confined to the prostate bed: Whole-pelvis radiation therapy (WPRT) reduced the risk of progression by 88% compared to prostate bed-only radiation
• For patients with lymph node involvement or distant metastases (N1/M1 disease): Adding androgen deprivation therapy (ADT) to radiation reduced progression risk by 63%

"These results underscore a fundamental evolution in how we approach biochemically recurrent prostate cancer, from anatomically based consensus guidelines to biologically informed, personalized treatment strategies," wrote Dr. Edward Christopher Dee of Memorial Sloan Kettering Cancer Center in an accompanying editorial.

The Precision Medicine Advantage

The UCLA data demonstrates several key advantages of PSMA PET/CT guidance:

Earlier Detection: PSMA PET/CT can identify recurrent disease at PSA levels where conventional imaging sees nothing, enabling earlier intervention when disease burden is lower.

Personalized Treatment Planning: Rather than treating all biochemical recurrences the same way, doctors can now tailor therapy based on the actual location and extent of disease:

• Patients with no visible disease can receive standard prostate bed radiation and often do very well
• Those with visible disease in lymph nodes can receive appropriately expanded radiation fields
• Patients with oligometastatic disease (a few distant spots) can have those areas specifically targeted

Avoiding Overtreatment: By identifying who actually needs whole-pelvis radiation or ADT, PSMA PET/CT helps spare patients from unnecessary treatment and side effects.

"PSMA PET/CT scans allow us to see exactly where cancer is and tailor treatment accordingly," said lead author Dr. Jeremie Calais. "Patients can get the therapy they need while avoiding unnecessary side effects, and even those with no visible disease can do very well with standard radiation."

Understanding the Patient Categories

The study categorized patients based on PSMA PET/CT findings:

• T0N0M0 (no visible disease): These patients had the best outcomes, suggesting that early salvage radiation when PSA first rises can be highly effective even without seeing cancer on the scan
• TrN0M0 (trace disease in prostate bed only): Outcomes were similar to patients with lymph node involvement, possibly because some had microscopic disease not visible on imaging
• N1M0 (lymph node involvement only): These patients benefited significantly from whole-pelvis radiation and ADT
• M1a-c (distant metastases): Patients with bone or distant organ involvement had less favorable outcomes, though many still benefited from targeted treatment

The Broader PSMA PET/CT Landscape

The UCLA study adds to a growing body of evidence supporting PSMA PET/CT in prostate cancer management:

FDA Approval and Availability: Two PSMA PET/CT agents are FDA-approved in the United States: Gallium-68 PSMA-11 (approved December 2020) and Pylarify (piflufolastat F-18, approved May 2021). A third agent, Posluma (flotufolastat F-18), received FDA approval in September 2023. These imaging agents are increasingly available at major medical centers and specialty imaging facilities.

Medicare Coverage: Following FDA approval, Medicare covers PSMA PET/CT for specific indications, including biochemical recurrence. Many private insurers have followed suit, though coverage policies vary.

Clinical Trial Evidence: Multiple prospective trials have validated PSMA PET/CT's detection capabilities:

• The CONDOR trial showed 63% detection rate at PSA 0.2-1.0 ng/mL
• The FALCON trial demonstrated PSMA PET/CT's superiority over conventional imaging
• The proPSMA trial found PSMA PET/CT had 92% accuracy vs. 65% for conventional imaging in detecting recurrent disease

Treatment Planning Impact: Studies consistently show that PSMA PET/CT changes treatment plans in 50-65% of cases compared to conventional imaging, often by identifying disease in unexpected locations or revealing more extensive disease than anticipated.

Integration into Clinical Practice

The findings support emerging treatment paradigms:

Early Salvage Radiation: Randomized trials have shown that initiating salvage radiation when PSA rises to 0.1-0.2 ng/mL improves outcomes compared to waiting for higher levels. PSMA PET/CT enhances this approach by identifying targets at these low PSA levels.

Oligometastatic Treatment: When PSMA PET/CT identifies a limited number of metastases (oligometastatic disease), stereotactic body radiation therapy (SBRT) can target these spots directly, potentially delaying systemic therapy and improving quality of life.

Risk Stratification: PSMA PET/CT findings help predict which patients need treatment intensification (WPRT, ADT, or both) versus those who can be managed with more conservative approaches.

Important Limitations and Considerations

While the UCLA results are encouraging, several caveats deserve attention:

Retrospective Design: This was a single-center, retrospective study rather than a randomized controlled trial. Selection bias could influence results—patients who received PSMA PET/CT at UCLA may differ from the general population.

Need for Prospective Validation: The authors acknowledge that prospective randomized trials are needed to confirm these findings. Several such trials are ongoing, including:

• PSMA-SRT (NCT03582774): Randomized trial of PSMA PET/CT-guided vs. conventional salvage radiation
• PATRON (NCT04557501): Comparing WPRT vs. prostate bed radiation in PSMA PET/CT-positive patients

Not a Cure-All: Even with PSMA PET/CT guidance, half of patients experienced progression within the follow-up period, underscoring that biochemical recurrence remains a challenging clinical scenario.

False Negatives Exist: PSMA PET/CT doesn't detect 100% of disease. Some patients categorized as "no visible disease" likely had microscopic metastases that became apparent later.

Variable Expression: Not all prostate cancers express PSMA equally. Some aggressive variants may have low PSMA expression and be missed by this imaging.

What This Means for Patients

If you're experiencing biochemical recurrence after surgery:

Discuss PSMA PET/CT with Your Doctor: Ask whether this imaging is appropriate for your situation, particularly if your PSA is rising from undetectable levels.

Earlier Is Often Better: The data support early salvage radiation (PSA 0.1-0.2 ng/mL) rather than waiting for higher levels. PSMA PET/CT can help guide this early intervention.

Treatment Individualization: PSMA PET/CT results should inform whether you need:

• Prostate bed-only radiation
• Whole-pelvis radiation
• Addition of ADT
• Treatment of oligometastatic disease with SBRT

Consider Your Center's Experience: PSMA PET/CT interpretation requires expertise. Centers with significant experience in PSMA imaging and radiation planning may offer advantages.

Insurance and Access: Check your insurance coverage for PSMA PET/CT. Medicare and many private insurers cover this imaging for biochemical recurrence, but prior authorization may be required.

The Road Ahead

Dr. Dee's editorial captures the significance of this shift: "PSMA PET imaging lets us move from one-size-fits-all radiation therapy in the secondary/salvage setting to treatment that's guided by the anatomy, and perhaps by extension, the actual biology of a patient's prostate cancer."

This evolution from consensus-based guidelines to biology-driven personalized treatment represents genuine progress in prostate cancer care. While questions remain about optimal patient selection, timing, and treatment intensification, the UCLA study provides real-world evidence that seeing the cancer—even at very low PSA levels—can meaningfully improve outcomes.

For the thousands of men who experience biochemical recurrence each year, PSMA PET/CT offers hope for more precise, effective treatment with potentially fewer unnecessary side effects. As prospective trials mature and clinical experience grows, this technology will likely become standard of care for managing post-prostatectomy PSA recurrence.

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Verified Sources and Formal Citations

1. Calais J, et al. "Long-Term Oncologic Outcomes of Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography–Guided Salvage Radiotherapy for Biochemical Recurrence After Radical Prostatectomy." Journal of the National Comprehensive Cancer Network 2026. https://jnccn.org (Article published February 2026)

2. Dee EC, et al. "PSMA PET/CT in Biochemically Recurrent Prostate Cancer: A Paradigm Shift Toward Precision Radiotherapy" [Editorial]. Journal of the National Comprehensive Cancer Network 2026. https://jnccn.org

3. Bankhead C. "Paradigm Shift for Evaluating, Treating Biochemical Recurrence in Prostate Cancer." MedPage Today, February 9, 2026. https://www.medpagetoday.com

4. National Comprehensive Cancer Network. "PSMA PET Imaging Shows Promise in Guiding Prostate Cancer Treatment" [Press Release]. February 2026. https://www.nccn.org

5. UCLA Health. "PSMA PET/CT Scans Improve Long-Term Outcomes for Prostate Cancer Patients" [Press Release]. February 2026. https://www.uclahealth.org

6. U.S. Food and Drug Administration. "FDA Approves First PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer." December 1, 2020. https://www.fda.gov/news-events/press-announcements/fda-approves-first-psma-targeted-pet-imaging-drug-men-prostate-cancer

7. U.S. Food and Drug Administration. "FDA Approves Second PSMA-Targeted PET Imaging Drug for Men with Prostate Cancer." May 27, 2021. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-second-psma-targeted-pet-imaging-drug-men-prostate-cancer

8. Morris MJ, et al. "Diagnostic Performance of 18F-DCFPyL-PET/CT in Men with Biochemically Recurrent Prostate Cancer: Results from the CONDOR Phase III, Multicenter Study." Clinical Cancer Research 2021;27(13):3674-3682. https://doi.org/10.1158/1078-0432.CCR-20-4573

9. Hofman MS, et al. "Prostate-specific Membrane Antigen PET-CT in Patients with High-risk Prostate Cancer Before Curative-intent Surgery or Radiotherapy (proPSMA): A Prospective, Randomised, Multicentre Study." The Lancet 2020;395(10231):1208-1216. https://doi.org/10.1016/S0140-6736(20)30314-7

10. Fendler WP, et al. "Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial." JAMA Oncology 2019;5(6):856-863. https://doi.org/10.1001/jamaoncol.2019.0096

11. Centers for Medicare & Medicaid Services. "National Coverage Determination (NCD) for Positron Emission Tomography (PET) Scans (220.6.26)." CMS.gov. https://www.cms.gov/medicare-coverage-database/view/ncd.aspx?NCDId=391

12. Vale CL, et al. "Adjuvant or Early Salvage Radiotherapy for the Treatment of Localised and Locally Advanced Prostate Cancer: A Prospectively Planned Systematic Review and Meta-analysis of Aggregate Data." The Lancet 2020;396(10260):1422-1431. https://doi.org/10.1016/S0140-6736(20)31952-8

13. ClinicalTrials.gov. "PSMA-PET/CT Guided Radiation Therapy in Treating Patients With Recurrent Prostate Cancer (PSMA-SRT)." NCT03582774. https://clinicaltrials.gov/study/NCT03582774

14. ClinicalTrials.gov. "Pelvic Radiotherapy After Prostate-Specific Membrane Antigen Positron Emission Tomography (PATRON)." NCT04557501. https://clinicaltrials.gov/study/NCT04557501

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This article is for educational purposes and should not replace consultation with your healthcare team. Treatment decisions should be made in partnership with physicians familiar with your individual case.