(UroToday.com) There has been significant progress in the last century in the treatment of advanced prostate cancer (Figure 1).

Figure 1- Treatment changes in Prostate cancer:

The older generation radioisotope treatments such as strontium, samarium, and radium were directed to areas of increased bone turnover in bone metastasis, and they were not prostate cancer-specific. They are not suitable for soft tissue metastasis, and the survival benefit was only proven for radium in metastatic castration-resistant prostate cancer (mCRPC) post docetaxel. There is also relevant nematotoxicity (strontium and samarium > radium).

In 2014 Prostate membrane antigen (PSMA)-lutetium was discovered, and in 2015 the first case report of LU-PSMA was published demonstrating prostate-specific antigen (PSA) reduction after two cycles of treatment1. Since then, there have been many retrospective studies assessing LU-PSMA (Table 1). These demonstrated significant heterogeneity, with no control arms, and limited information on radiographic progression-free survival, and overall survival.

Table 1 – Retrospective studies of LU-PSMA:

In 2018 a single-center, single-arm, phase 2 study assessed the role of -LU-PSMA in 50 mCRPC patients who received prior therapy with docetaxel, cabazitaxel, and/or ARAT2. The primary endpoints were PSA response, toxicity, imaging response, and patient-reported quality of life. The secondary endpoints included overall survival and progression-free survival. The results were quite impressive, showing a benefit in PSA decline, overall survival, and PSA progression-free survival (Figure 2). This treatment has been shown to result in 12-13.3 months of overall survival benefit (Table 2).

Figure 2- LU-PSMA results:

Table 2 – LU-PSMA overall survival benefit:

The prospective TheraP-trial (ANZUP 1603) compared LU-PSMA to cabazitaxel in mCRPC patients post docetaxel with progressive disease (Figure 3). This study demonstrated a clear significant benefit in the LU-PSMA treated patients in the PSA>=50% response parameter (66% vs. 37%) (Figure 4). The study also demonstrated a response in PSA progression-free survival as well (figure 5). This was the first prospective controlled trial of LU-PSMA with an active control arm showing significantly better PSA response and PSA progression-free survival in patients treated with LU-PSMA. The secondary endpoints are still being analyzed. The adverse events were significantly lower with LU-PSMA compared to patients treated with the best standard of care only.

Figure 3 – TheraP- Trial design:

Figure 4 – TheraP trial PSA >=50% response rates:

Figure 5 – PSA progression-free survival:

Another ongoing study is the VISION study, which is a prospective randomized controlled trial comparing LU-PSMA+ best standard of care to the best standard of care alone (Figure 6).

Figure 6 – VISION study design:

In summary, there has been a phase 2 single-arm study and controlled trials showing that photo-ligand therapy is effective in heavily pretreated patients. It has resulted in PSA>50% reduction in up to 64% of patients with an overall survival of 13.3 months. It has moderate toxicity, mainly grade 1 and 2 dry eyes, moderate hematotoxicity, and diarrhea.

It is suitable only for select cases with high PSMA expression and no PSMA/FDG discordance. Currently, there is no overall survival or radiographic progression-free survival clear advantage, and its availability is still limited.



1. Kratochwil C, Giesel FL, Eder M, et al. [¹⁷⁷Lu]Lutetium-labelled PSMA ligand-induced remission in a patient with metastatic prostate cancer. European journal of nuclear medicine and molecular imaging 2015; 42(6): 987-8.
2. Hofman MS, Violet J, Hicks RJ, et al. [(177)Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. The Lancet Oncology 2018; 19(6): 825-33.

Presented by: Thomas Steuber, MD, Professor, Chief Physician, Department of Urology, Prostate Cancer Center, Martini Klinik, the University Hospital Hamburg-Eppendorf, Hamburg, Germany

Written by: Hanan Goldberg, MD, MSc., Urology Department, SUNY Upstate Medical University, Syracuse, NY, USA, @GoldbergHanan at the 35th Annual EAU Congress, 2020 Virtual Program #EAU20, July 17-19, 2020.