Copy number variation of urine exfoliated cells by low-coverage whole genome sequencing for diagnosis of prostate adenocarcinoma: a prospective cohort study.

BACKGROUND: Non-invasive, especially the urine-based diagnosis of prostate cancer (PCa) remains challenging. Although prostate cancer antigen (PSA) is widely used in prostate cancer screening, the false positives may result in unnecessary invasive procedures. PSA elevated patients are triaged to further evaluation of free/total PSA ratio (f/t PSA), to find out potential clinically significant PCa before undergoing invasive procedures. Genomic instability, especially chromosomal copy number variations (CNVs) were proved much more tumor specific. Here we performed a prospective study to evaluate the diagnostic value of CNV via urine-exfoliated cell DNA analysis in PCa. METHODS: We enrolled 28 PSA elevated patients (≥ 4 ng/ml), including 16 PCa, 9 benign prostate hypertrophy (BPH) and 3 prostatic intraepithelial neoplasia (PIN). Fresh initial portion urine was collected after hospital admission. Urine exfoliated cell DNA was analyzed by low coverage Whole Genome Sequencing, followed by CNV genotyping by the prostate cancer chromosomal aneuploidy detector (ProCAD). CNVs were quantified in absolute z-score (|Z|). Serum free/total PSA ratio (f/t PSA) was reported altogether. RESULTS: In patients with PCa, the most frequent CNV events were chr3q gain (n = 2), chr8q gain (n = 2), chr2q loss (n = 4), and chr18q loss (n = 3). CNVs were found in 81.2% (95% Confidence Interval (CI) 53.7-95.0%) PCa. No CNV was identified in BPH patients. A diagnosis model was established by incorporating all CNVs. At the optimal cutoff of |Z|≥ 2.50, the model reached an AUC of 0.91 (95% CI 0.83-0.99), a sensitivity of 81.2% and a specificity of 100%. The CNV approach significantly outperformed f/t PSA (AUC = 0.62, P = 0.012). Further analyses showed that the CNV positive rate was significantly correlated with tumor grade. CNVs were found in 90.9% (95% CI 57.1-99.5%) high grade tumors and 60.0% (95% CI 17.0-92.7%) low grade tumors. No statistical significance was found for patient age, BMI, disease history and family history. CONCLUSIONS: Urine exfoliated cells harbor enriched CNV features in PCa patients. Urine detection of CNV might be a biomarker for PCa diagnosis, especially in terms of the clinically significant high-grade tumors.

Multimodal Treatment Combining Salvage Surgery-Assisted Chemotherapy and Checkpoints Blockade Immunotherapy Achieves Complete Remission on a Recurrent Penile Cancer Patient: A Case Report.

Penile squamous cell carcinoma (pSCC) is a rare disease in developed countries. pSCC causes a severe health problem and social burden in developing countries. We reported a 49-year-old male recurrent pSCC patient with medium PD-L1 expression and low TMB. The patient obtained complete response after multimodal therapy (MMT). The clinical manifestation is a recurrence in the right groin with nearly ruptured pSCC. He had partial resection of penile cancer plus bilateral groin lymph node dissection and pelvic lymph node dissection during the first operation. Pathology of the recurrent tumor showed fibrous tissue with cancer infiltration and necrosis. We used MMT, including resection of palliative right inguinal metastases, four cycles of paclitaxel+bleomycin+cisplatin, and continuous sintilimab to treat the patient. The patient had a complete response (CR) after four cycles of therapy and sustained CR for 18 months with continuous sintilimab, showing a good tolerance and acceptable toxicity. This is the first case presenting a complete response in a relapsed pSCC patient. These results suggest that MMT is worth exploring.

Efficacy and Safety of Androgen-Deprivation Therapy Combined with Docetaxel Plus Prednisone in High-Burden Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: The aim of this study was to evaluate the efficacy and safety of hormonal and synchronous docetaxel plus prednisone (DocP) in metastatic hormone-sensitive prostate cancer (mHSPC). METHODS: One hundred fifty-one cases with high-burden mHSPC diagnosed at 1 single center from January 2014 to August 2018 were analyzed retrospectively. Among them, 85 cases received androgen-deprivation therapy (ADT) within 3 months, along with 6 cycles of docetaxel + prednisone (treatment group), whereas 66 received ADT alone (control group). The primary end point was the median overall survival (OS), while the secondary outcomes included prostate-specific antigen (PSA) progression-free survival (PFS), radiographic PFS, and the proportion of PSA falling to 0.2 ng/mL. RESULTS: A total of 151 patients were included and followed up for a median of 34 months in this study. The median OS time in the treatment group was unavailable, but it was remarkably longer than that of the control group (P<0.001). In addition, the PFS of PSA in the treatment group and control group was 17.9 months and 9.2 months, respectively (P<0.001). Meanwhile, the radiographic PFS was 43 months in the treatment group and 19.8 months in the control group, respectively (P<0.001). The proportions of PSA falling to 0.2 ng/mL were 53.7% and 23.3%, respectively (P<0.001). However, there was no significant difference in the incidence of ≥3 toxic side effects between these 2 groups (P=0. 21). CONCLUSION: ADT combined with 6 cycles of docetaxel + prednisone chemotherapy benefits patients diagnosed with high-burden mHSPC in terms of the OS, PFS of PSA and radiographic, and the ratio of PSA falling to 0.2 ng/mL.