Highlights from the 15th Shanghai Urologic Oncology Academic Conference
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Editor’s Note: Over the past decade, the treatment landscape of prostate cancer has undergone profound transformation, with the rise of radioligand therapy (RLT) emerging as one of the most notable advances. Initially developed as a salvage option for end-stage disease, RLT is now steadily moving into earlier disease settings, demonstrating substantial clinical potential.
At the recent Shanghai Urologic Oncology Academic Conference, Oncology Frontier – Urology Frontier invited Professor Renu Eapen from the Peter MacCallum Cancer Centre, Australia, to share her in-depth insights into the Lu-PSMA research program and the latest developments of RLT in metastatic hormone-sensitive prostate cancer (mHSPC).
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Oncology Frontier – Urology Frontier
Question: In recent years, what major advances have been made in the field of radioligand therapy (RLT) for prostate cancer? In particular, how might the recently reported PSMAddition study influence future clinical practice?
Professor Renu Eapen: The RLT landscape has evolved dramatically over the past ten years. The first prospective study in this field was the LuPSMA trial, led by Professor Michael Hofman at our center. This single-arm phase II study evaluated ^177Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer (mCRPC) who had failed multiple lines of therapy, with a median of four prior treatment regimens.
One of the defining features of this trial was the use of dual PSMA/FDG PET-CT imaging for precision screening, which excluded patients with low PSMA expression or discordant disease (FDG-positive but PSMA-negative lesions). The outcomes were impressive: 64% of patients achieved a PSA decline of at least 50%, median overall survival reached 13.3 months, and patients experienced meaningful reductions in bone pain along with improved quality of life. This foundational work directly paved the way for the TheraP and VISION trials, which confirmed that ^177Lu-PSMA-617 provides robust biochemical responses and quality-of-life benefits even in late-stage, heavily pretreated patients.
The VISION study was a landmark randomized, open-label phase III trial comparing ^177Lu-PSMA-617 plus best standard of care (BSoC) versus BSoC alone in PSMA-positive mCRPC patients who had previously received at least one androgen receptor pathway inhibitor (ARPI) and taxane-based chemotherapy. The results demonstrated a significant improvement in median overall survival (15.3 vs. 11.3 months) and radiographic progression-free survival (8.7 vs. 3.4 months). These findings confirmed that RLT significantly reduces the risk of death, ultimately leading to FDA approval of Pluvicto and establishing RLT as a standard of care for advanced prostate cancer.
The TheraP study (ANZUP 1603) was the world’s first randomized, multicenter phase II trial to directly compare RLT with standard chemotherapy. It provided strong evidence supporting ^177Lu-PSMA-617 as a second-line treatment option in mCRPC. The trial enrolled 200 patients with disease progression after docetaxel. Patients were randomized to receive either ^177Lu-PSMA-617 or cabazitaxel. Unlike VISION, TheraP employed more stringent dual PSMA/FDG PET screening, requiring a PSMA SUVmax ≥ 20. The results showed a significantly higher PSA response rate in the Lu-PSMA group (66% vs. 37%) and a higher proportion of patients remaining progression-free at 12 months (19% vs. 3%). Importantly, grade 3–4 adverse events were substantially lower in the Lu-PSMA group (33% vs. 53%), accompanied by superior quality-of-life outcomes.
At present, RLT is being actively investigated earlier in the treatment continuum.
- ENZA-P Study: This phase II trial evaluated the combination of RLT with enzalutamide in ARPI-naïve mCRPC patients. The combination reduced the risk of disease progression by 57%, with a PSA-50 response rate of 93%, compared with 68% for enzalutamide alone.
- PSMAfore Study: This phase III trial moved RLT into the pre-chemotherapy (taxane-naïve) setting. Compared with switching to an alternative ARPI, ^177Lu-PSMA-617 significantly improved radiographic progression-free survival (12.0 vs. 5.6 months) and reduced the risk of disease progression by 59%.
- UpFrontPSMA Study: This pioneering phase II study evaluated RLT in patients with high-volume mHSPC. Two cycles of Lu-PSMA followed by six cycles of docetaxel resulted in a significantly higher proportion of patients achieving undetectable PSA levels (≤0.2 ng/mL) at 48 weeks (41% vs. 16%), as well as prolonged PSA progression-free survival (31 vs. 20 months).
- PSMAddition Study: This ongoing international phase III trial represents the leading edge of RLT research in the mHSPC setting. It is evaluating a triplet regimen—ADT plus a novel ARPI plus ^177Lu-PSMA-617—versus standard doublet therapy. The objective is to use radioligand therapy to precisely target micrometastatic disease at an early stage, reduce tumor burden, and delay progression to castration-resistant disease.
In summary, Lu-PSMA is well tolerated and demonstrates meaningful activity across multiple stages of prostate cancer. Going forward, research will continue to focus on precision patient selection and optimal treatment sequencing, particularly in the mHSPC setting, to delay disease progression as effectively as possible.
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Oncology Frontier – Urology Frontier
Question: Antibody–drug conjugates (ADCs) have shown great promise in the treatment of solid tumors in recent years. How do you view the potential role of these novel agents in prostate cancer?
Professor Renu Eapen: ADCs and radioligand therapies targeting different antigens in prostate cancer represent a highly attractive area of research. Several ADC candidates directed against various targets are currently being evaluated in phase I–II clinical trials in China, and the preliminary results are encouraging.
The key challenge, however, lies in identifying the patient populations most likely to benefit. For PSMA-targeted therapies, PSMA PET-CT has become a mature and reliable screening tool. In contrast, ADC development requires the identification and validation of corresponding biomarkers to guide patient selection. In addition, conducting neoadjuvant studies with ADCs is critically important. Such studies will help us better understand their mechanisms of action and the underlying tumor biology, thereby laying a strong scientific foundation for their future clinical application in prostate cancer.
Professor Renu Eapen
