Clinico-Pathological Factors and AR-LBD Mutations in Early and Late Castration-Resistant Prostate Cancer

Monu Deswal,1 Durgavati Yadav,1 Vinay Kumar,2 Meenakshi Meenu,3 Pranay Tanwar,4 Shivani Srivastava,5 Prabhjot Singh,1 Kumar Sandeep6 1Department of Urology, All India Institute of Medical Sciences, New Delhi, India; 2Heart and Vascular Institute, Pennsylvania State University, Hershey Medical Center, Hershey, PA, USA; 3Department of Pharmacology, All India Institute of Medical Sciences, Bilaspur, Himachal Pradesh, India; 4Lab Oncology Unit, Dr.B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India; 5Department of Pathology, Yale University School of Medicine, New Haven, CT, USA; 6Preventive Oncology, Dr.B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, IndiaCorrespondence: Prabhjot Singh, Department of Urology, All India Institute of Medical Sciences, New Delhi, India, Email [email protected] Kumar Sandeep, Preventive Oncology, Dr.B.R.A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India, Email [email protected]: Prostate cancer (PCa) is not well understood because of its enormous biological heterogeneity and unreliable progression. We conducted this retrospective analysis to examine the variables predicting early and late progression to castration-resistant PCa (CRPC) for better management of this disease.Methods: This single institutional retrospective study was conducted from January 2018 to January 2022. A total of 98 consecutive men meeting with the diagnosis of CRPC as per the inclusion criteria were included in the study and were stratified in four quartiles on the basis of time to CRPC (time to castration resistance [TTCR]) development. Early CRPC (1st quartile, TTCR = 6– 12 months) and late CRPC (4th quartile, TTCR = 38– 120 months) were then compared on the basis of different clinical, pathological and AR-LBD sequence to find the correlation with response duration.Results: Median time to develop castration resistance was 25 ± 26.44 months. The mean age of the patients was 66.8 ± 9.20 years and median baseline PSA was calculated 100± 685.06 ng/mL respectively. Higher Gleason score (≥ 7– 10) was found to be significantly associated with early development of CRPC (p< 0.001) and lower nadir PSA was significantly indicating late CRPC progression (p< 0.005). No mutations were found in androgen receptor exon-5, 6, 7 except a homozygous mutation in the 7th intronic region, which is involved in splice variants formation playing noteworthy role in CRPC development.Conclusion: Time for metastatic PCa to CRPC ranges from 6– 120 months revealing its heterogeneous nature. Early age presentation in the clinic and high initial PSA and high grade (GS> 7) at diagnosis were positively associated with early CRPC while lower nadir PSA was correlated with late CRPC progression. No remarkable genomic mutations were discovered. Therefore, more data are needed and further research is required with large no. of patients to discover the predictive prognostic biomarkers for better patients’ management.Keywords: prostate cancer, castration resistance, early and late progression, PSA, androgen receptor, PCa