Abstract

Background

Urological cancers, including prostate, bladder, kidney, testicular, and penile cancers, often fail to show symptoms or show only nonspecific symptoms at early stages. This leads to delayed diagnosis, treatment decisions, and outcomes. Circulating tumor cells (CTCs) predict the outcome in metastatic prostate cancer (PC). Furthermore, in bladder cancer, CTC positivity is linked to muscle invasion, higher recurrence risk, and worse clinical outcomes. CTC PD-L1 expression could evade immune elimination. In spite of complete remission, a higher percentage of patients are known to recur in urothelial cancers. CTCs acting as minimal cellular residual disease (MCRD) are highly implicated, knowing their capacity to be dormant systemically with extravasation and invasion to distant organs. We analyzed the presence of CTCs with PD-L1 over-expression in urological cancers at baseline and follow-ups.

Methods

Retrospectively, a total of 359 urological cancer patients were evaluated for CTC positivity, including 307 at baseline and 52 follow-up samples. The cancer type distribution was prostate cancer (n = 139), bladder (n = 188), kidney (n = 10), testes (n = 2), penis (n = 8), urothelial (n = 12), etc. Ninety-five percent of the patients were male (n = 293) and 5% were female (n = 14), with most patients aged 61 to 80 years. CTCs expressing PD-L1, positive CTCs, and CTC clusters were analyzed using OncoDiscover® PD-L1 markers and a Zeiss fluorescence automated microscope. Demographics, cancer mean distribution, and CTC and cluster frequency were analyzed.

Results

Of the 359 patients, CTCs were detected in 68.2% (245/359) of patients, while PD-L1 over-expression on CTCs was present in 49.9% (179/359) of patients. However, CTC clusters were uncommon and occurred in 7.2% (26/359) of patients. Across cancer types (total CTCs = 436), prostate cancer accounted for higher CTCs with a mean CTC distribution of 2.18, while bladder was 0.74, urothelial 0.34, testes 0.18, kidney 0.74, and penis 0.38, respectively. CTC PD-L1 was highest in prostate cancer (46.1%) compared to other cancers, and CTC cluster prevalence was 1.8% in prostate cancer, urothelial (0.9%), and bladder (0.2%) cancers. In CTC-positive cases, 56.3% of patients had only one CTC, 27.8% showed two CTCs, and 8.2% had three. The mean across all patients was 0.6 for CTCs, 0.3 for CTC-PD-L1 positive, and 0.1 for clusters.

Conclusions

CTCs with PD-L1-positive overexpression were observed across urological cancers, being particularly higher in prostate cancer compared to bladder, kidney, and penis cancers. Many patients are known to recur in spite of complete remission, possibly due to the presence of aggressive CTCs in circulation that could evade the immune system. More studies assessing the presence of CTCs with PD-L1 expression are justified in urological cancers for minimal cellular residual disease and as prognostication.