Outcomes of PSMA radioligand therapy in lymph node-only metastatic prostate cancer: seven-year results from a single centre

Abstract Background Outcomes of Lu-PSMA radioligand therapy in lymph node (LN) only metastatic prostate cancer remain underreported and existing series are small with short follow-up. We report longer-term outcomes from a single tertiary centre. Methods We retrospectively reviewed patients treated with prostate specific membrane antigen (PSMA) radioligand theranostics (RLT) for LN-only metastatic prostate cancer between May 2017–May 2025, defined as PSMA-avid nodal disease on ⁶⁸Ga-PSMA PET/CT without bone or visceral metastases. Outcomes were analysed overall and across three subgroups: metastatic hormone-sensitive disease (mHSPC), mCRPC without prior chemotherapy, and mCRPC with prior chemotherapy. PSA response, PCWG2 progression, prostate cancer-specific survival (PCSS) and toxicity were assessed. Results Of 366 patients treated with ¹⁷⁷Lu-PSMA RLT, 35 had LN-only disease, 33 were suitable for analysis. The median follow-up time for those still alive at time of analysis was 48 months (IQR 23–74 months). The median number of treatments was three. A PSA decline of ≥ 50% was achieved in 8/11 (73%) patients with mHSPC, all 11 (100%) mCRPC with no prior chemotherapy, and 5/11 (45%) mCRPC with chemotherapy. For those with mHSPC, six patients developed PSA progression with the median time to progression being 47 months (95% CI: 6.9 – not evaluable (NE)). The median time to prostate cancer death was 56 months (95% CI: 26 – NE). Between-group log-rank p values were 0.082 for PSA progression-free survival and 0.003 for prostate cancer-specific survival. No serious haematological or renal toxicity was observed within three months. Conclusions In the largest single-centre LN-only ¹⁷⁷Lu-PSMA RLT series with extended follow-up, treatment produced high PSA response rates and favourable survival in mHSPC and chemotherapy-naïve mCRPC patients, with minimal toxicity. These findings support prospective evaluation of earlier introduction of Lu-PSMA RLT in LN-only disease.