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Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?

Year 2024, Volume: 41 Issue: 3, 474 - 478, 30.09.2024

Abstract

Measuring PD-1 expression may help select patients with prostate cancer for not favorable on intensification of treatment. The question of whether similar benefits were derived from androgen-deprivation therapy (ADT) alone, or upfront chemotherapy or targeted therapies, remained an enigma. The key question was whether unnecessary escalation of concurrent additional androgen-targeted therapy or chemotherapy could be halted. These serious and potentially life-threatening considerations required carefully designed clinical trials to be resolved. The study aimed to evaluate the role of PD-1 in predicting outcomes from prostate cancer management with our then-current intensification treatment strategy. In total, 20 patients diagnosed with prostate cancer at RSUP Dr. Sardjito were enrolled between 2015 and 2021. The expressions of PD-1 in primary tumors were quantified using quantitative real-time polymerase chain reaction. Data were analyzed descriptively in percentages followed by bivariate and multivariate analyses with p-value < 0.05 considered significant. The mean age of patients enrolled in this study was 71.6 5± 8.76 years, and the mean of prostate-specific antigen in patients was 96.25 ± 83.01 ng/ml. Compared to the 25th percentile, higher expression of PD-1 exhibited greater prognostic value than the variable of shorter time to castration-resistant prostate cancer (CRPC). (60 months vs. 21.7 ± 5.58 months, pvalue: 0.005). This pilot study demonstrates that high expression of PD-1 is a promising biomarker for selecting patients who might benefit from intensification therapy.

References

  • Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
  • Division of Urology, Dr. Sardjito General Hospital, Public Health and Nursing UGM Faculty of Medicine, Yogyakarta, Indonesia, Soerohardjo I, Zulfiqqar A, et al. The Combined Effect of Downregulated RB1 and Overexpressed lncRNA SSTRS-AS1 on Prediction Time to Castration-Resistant Prostate Cancer: Indonesian Cohort Studies. Türk Ürol DergisiTurkish J Urol. 2022;48(2):112-117. doi:10.5152/tud.2022.21282
  • Rush HL, Murphy L, Morgans AK, et al. Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2022;40(8):825-836. doi:10.1200/JCO.21.00728
  • Naqvi SAA, Riaz ZB, Riaz A, et al. Indirect comparisons of triplet therapy as compared to novel hormonal therapy doublets in patients with metastatic castration sensitive prostate cancer. J Clin Oncol. 2022;40(16_suppl):5083-5083. doi:10.1200/JCO.2022.40.16_suppl.5083
  • Chen K, McVey A, Kasivisvanathan V, Jenjitranant P, Azad A, Murphy DG. Re: Darolutamide and Survival in Metastatic, Hormone-sensitive Prostate Cancer. Eur Urol. 2022;82(1):146-147. doi:10.1016/j.eururo.2022.03.018
  • Yuri P, Shigemura K, Kitagawa K, et al. Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients’ survival and responses to androgen deprivation therapies in Indonesian patients cohort. Prostate Int. 2020;8(2):62-69. doi:10.1016/j.prnil.2019.12.001.
  • Modena A, Ciccarese C, Iacovelli R, et al. Immune checkpoint inhibitors and prostate cancer: a new frontier? Oncol Rev. Published online April 15, 2016. doi:10.4081/oncol.2016.293
  • Brunello L. AR in immunotherapy. Nat Rev Cancer. 2022;22(6):319-319. doi:10.1038/s41568-022-00476-z
  • Agha R, Abdall-Razak A, Crossley E, et al. STROCSS 2019 Guideline: Strengthening the reporting of cohort studies in surgery. Int J Surg. 2019;72:156-165. doi:10.1016/j.ijsu.2019.11.002
  • Brierley J, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours. Eighth edition. John Wiley & Sons, Inc; 2017.
  • Shiao SL, Chu GCY, Chung LWK. Regulation of prostate cancer progression by the tumor microenvironment. Cancer Lett. 2016;380(1):340-348. doi:10.1016/j.canlet.2015.12.022
  • Appleman LJ, Kolinsky MP, Berry WR, et al. KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New data after an additional 1 year of follow-up. J Clin Oncol. 2021;39(6_suppl):10-10. doi:10.1200/JCO.2021.39.6_suppl.10
  • Fizazi K, González Mella P, Castellano D, et al. CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer. J Clin Oncol. 2021;39(6_suppl):12-12. doi:10.1200/JCO.2021.39.6_suppl.12
  • Agarwal N, Loriot Y, McGregor BA, et al. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study. J Clin Oncol. 2020;38(15_suppl):5564-5564. doi:10.1200/JCO.2020.38.15_suppl.5564
  • Gevensleben H, Dietrich D, Golletz C, et al. The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer. Clin Cancer Res. 2016;22(8):1969-1977. doi:10.1158/1078-0432.CCR-15-2042
  • Mercader M, Bodner BK, Moser MT, et al. T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci. 2001;98(25):14565-14570. doi:10.1073/pnas.251140998
  • Hsu J, Hodgins JJ, Marathe M, et al. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J Clin Invest. 2018;128(10):4654-4668. doi:10.1172/JCI99317
  • Barry KC, Hsu J, Broz ML, et al. A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments. Nat Med. 2018;24(8):1178-1191. doi:10.1038/s41591-018-0085-8
  • Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5(12):1365-1369. doi:10.1038/70932
  • Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation. J Exp Med. 2000;192(7):1027-1034. doi:10.1084/jem.192.7.1027
  • Montironi R, Pomante R, Diamanti L, Magi-Galluzzi C. Apoptosis in Prostatic Adenocarcinoma following Complete Androgen Ablation. Urol Int. 1998;60(Suppl. 1):25-30. doi:10.1159/000056542
  • Rovere P, Vallinoto C, Bondanza A, et al. Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol Baltim Md 1950. 1998;161(9):4467-4471.
  • Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392(6671):86-89. doi:10.1038/32183
  • Albert ML, Pearce SF, Francisco LM, et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998;188(7):1359-1368. doi:10.1084/jem.188.7.1359
  • Jain RK, Safabakhsh N, Sckell A, et al. Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor. Proc Natl Acad Sci. 1998;95(18):10820-10825. doi:10.1073/pnas.95.18.10820
  • Armas OA, Aprikian AG, Melamed J, et al. Clinical and Pathobiological Effects of Neoadjuvant Total Androgen Ablation Therapy on Clinically Localized Prostatic Adenocarcinoma: Am J Surg Pathol. 1994;18(10):979-991. doi:10.1097/00000478-199410000-00002
  • Montironi R, Schulman CC. Pathological changes in prostate lesions after androgen manipulation. J Clin Pathol. 1998;51(1):5-12. doi:10.1136/jcp.51.1.5
  • Harris MT, Feldberg RS, Lau KM, Lazarus NH, Cochrane DE. Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate. The Prostate. 2000;44(1):19-25. doi:10.1002/1097-0045(20000615)44:1<19::AID-PROS3>3.0.CO;2-S
  • Grossman CJ. Interactions Between the Gonadal Steroids and the Immune System. Science. 1985;227(4684):257-261. doi:10.1126/science.3871252
  • Ellis TM, Moser MT, Le PT, Flanigan RC, Kwon ED. Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. Int Immunol. 2001;13(4):553-558. doi:10.1093/intimm/13.4.553
  • Singh J, Sohal SS, Ahuja K, et al. Levels of plasma cytokine in patients undergoing neoadjuvant androgen deprivation therapy and external beam radiation therapy for adenocarcinoma of the prostate. Ann Transl Med. 2020;8(10):636-636. doi:10.21037/atm-19-1913
  • Wang C, Zhang Y, Gao WQ. The evolving role of immune cells in prostate cancer. Cancer Lett. 2022;525:9-21. doi:10.1016/j.canlet.2021.10.027
Year 2024, Volume: 41 Issue: 3, 474 - 478, 30.09.2024

Abstract

References

  • Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
  • Division of Urology, Dr. Sardjito General Hospital, Public Health and Nursing UGM Faculty of Medicine, Yogyakarta, Indonesia, Soerohardjo I, Zulfiqqar A, et al. The Combined Effect of Downregulated RB1 and Overexpressed lncRNA SSTRS-AS1 on Prediction Time to Castration-Resistant Prostate Cancer: Indonesian Cohort Studies. Türk Ürol DergisiTurkish J Urol. 2022;48(2):112-117. doi:10.5152/tud.2022.21282
  • Rush HL, Murphy L, Morgans AK, et al. Quality of Life in Men With Prostate Cancer Randomly Allocated to Receive Docetaxel or Abiraterone in the STAMPEDE Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2022;40(8):825-836. doi:10.1200/JCO.21.00728
  • Naqvi SAA, Riaz ZB, Riaz A, et al. Indirect comparisons of triplet therapy as compared to novel hormonal therapy doublets in patients with metastatic castration sensitive prostate cancer. J Clin Oncol. 2022;40(16_suppl):5083-5083. doi:10.1200/JCO.2022.40.16_suppl.5083
  • Chen K, McVey A, Kasivisvanathan V, Jenjitranant P, Azad A, Murphy DG. Re: Darolutamide and Survival in Metastatic, Hormone-sensitive Prostate Cancer. Eur Urol. 2022;82(1):146-147. doi:10.1016/j.eururo.2022.03.018
  • Yuri P, Shigemura K, Kitagawa K, et al. Increased tumor-associated macrophages in the prostate cancer microenvironment predicted patients’ survival and responses to androgen deprivation therapies in Indonesian patients cohort. Prostate Int. 2020;8(2):62-69. doi:10.1016/j.prnil.2019.12.001.
  • Modena A, Ciccarese C, Iacovelli R, et al. Immune checkpoint inhibitors and prostate cancer: a new frontier? Oncol Rev. Published online April 15, 2016. doi:10.4081/oncol.2016.293
  • Brunello L. AR in immunotherapy. Nat Rev Cancer. 2022;22(6):319-319. doi:10.1038/s41568-022-00476-z
  • Agha R, Abdall-Razak A, Crossley E, et al. STROCSS 2019 Guideline: Strengthening the reporting of cohort studies in surgery. Int J Surg. 2019;72:156-165. doi:10.1016/j.ijsu.2019.11.002
  • Brierley J, Gospodarowicz MK, Wittekind C, eds. TNM Classification of Malignant Tumours. Eighth edition. John Wiley & Sons, Inc; 2017.
  • Shiao SL, Chu GCY, Chung LWK. Regulation of prostate cancer progression by the tumor microenvironment. Cancer Lett. 2016;380(1):340-348. doi:10.1016/j.canlet.2015.12.022
  • Appleman LJ, Kolinsky MP, Berry WR, et al. KEYNOTE-365 cohort B: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)–pretreated patients with metastatic castration-resistant prostate cancer (mCRPC)—New data after an additional 1 year of follow-up. J Clin Oncol. 2021;39(6_suppl):10-10. doi:10.1200/JCO.2021.39.6_suppl.10
  • Fizazi K, González Mella P, Castellano D, et al. CheckMate 9KD Arm B final analysis: Efficacy and safety of nivolumab plus docetaxel for chemotherapy-naïve metastatic castration-resistant prostate cancer. J Clin Oncol. 2021;39(6_suppl):12-12. doi:10.1200/JCO.2021.39.6_suppl.12
  • Agarwal N, Loriot Y, McGregor BA, et al. Cabozantinib in combination with atezolizumab in patients with metastatic castration-resistant prostate cancer: Results of cohort 6 of the COSMIC-021 study. J Clin Oncol. 2020;38(15_suppl):5564-5564. doi:10.1200/JCO.2020.38.15_suppl.5564
  • Gevensleben H, Dietrich D, Golletz C, et al. The Immune Checkpoint Regulator PD-L1 Is Highly Expressed in Aggressive Primary Prostate Cancer. Clin Cancer Res. 2016;22(8):1969-1977. doi:10.1158/1078-0432.CCR-15-2042
  • Mercader M, Bodner BK, Moser MT, et al. T cell infiltration of the prostate induced by androgen withdrawal in patients with prostate cancer. Proc Natl Acad Sci. 2001;98(25):14565-14570. doi:10.1073/pnas.251140998
  • Hsu J, Hodgins JJ, Marathe M, et al. Contribution of NK cells to immunotherapy mediated by PD-1/PD-L1 blockade. J Clin Invest. 2018;128(10):4654-4668. doi:10.1172/JCI99317
  • Barry KC, Hsu J, Broz ML, et al. A natural killer–dendritic cell axis defines checkpoint therapy–responsive tumor microenvironments. Nat Med. 2018;24(8):1178-1191. doi:10.1038/s41591-018-0085-8
  • Dong H, Zhu G, Tamada K, Chen L. B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion. Nat Med. 1999;5(12):1365-1369. doi:10.1038/70932
  • Freeman GJ, Long AJ, Iwai Y, et al. Engagement of the Pd-1 Immunoinhibitory Receptor by a Novel B7 Family Member Leads to Negative Regulation of Lymphocyte Activation. J Exp Med. 2000;192(7):1027-1034. doi:10.1084/jem.192.7.1027
  • Montironi R, Pomante R, Diamanti L, Magi-Galluzzi C. Apoptosis in Prostatic Adenocarcinoma following Complete Androgen Ablation. Urol Int. 1998;60(Suppl. 1):25-30. doi:10.1159/000056542
  • Rovere P, Vallinoto C, Bondanza A, et al. Bystander apoptosis triggers dendritic cell maturation and antigen-presenting function. J Immunol Baltim Md 1950. 1998;161(9):4467-4471.
  • Albert ML, Sauter B, Bhardwaj N. Dendritic cells acquire antigen from apoptotic cells and induce class I-restricted CTLs. Nature. 1998;392(6671):86-89. doi:10.1038/32183
  • Albert ML, Pearce SF, Francisco LM, et al. Immature dendritic cells phagocytose apoptotic cells via alphavbeta5 and CD36, and cross-present antigens to cytotoxic T lymphocytes. J Exp Med. 1998;188(7):1359-1368. doi:10.1084/jem.188.7.1359
  • Jain RK, Safabakhsh N, Sckell A, et al. Endothelial cell death, angiogenesis, and microvascular function after castration in an androgen-dependent tumor: Role of vascular endothelial growth factor. Proc Natl Acad Sci. 1998;95(18):10820-10825. doi:10.1073/pnas.95.18.10820
  • Armas OA, Aprikian AG, Melamed J, et al. Clinical and Pathobiological Effects of Neoadjuvant Total Androgen Ablation Therapy on Clinically Localized Prostatic Adenocarcinoma: Am J Surg Pathol. 1994;18(10):979-991. doi:10.1097/00000478-199410000-00002
  • Montironi R, Schulman CC. Pathological changes in prostate lesions after androgen manipulation. J Clin Pathol. 1998;51(1):5-12. doi:10.1136/jcp.51.1.5
  • Harris MT, Feldberg RS, Lau KM, Lazarus NH, Cochrane DE. Expression of proinflammatory genes during estrogen-induced inflammation of the rat prostate. The Prostate. 2000;44(1):19-25. doi:10.1002/1097-0045(20000615)44:1<19::AID-PROS3>3.0.CO;2-S
  • Grossman CJ. Interactions Between the Gonadal Steroids and the Immune System. Science. 1985;227(4684):257-261. doi:10.1126/science.3871252
  • Ellis TM, Moser MT, Le PT, Flanigan RC, Kwon ED. Alterations in peripheral B cells and B cell progenitors following androgen ablation in mice. Int Immunol. 2001;13(4):553-558. doi:10.1093/intimm/13.4.553
  • Singh J, Sohal SS, Ahuja K, et al. Levels of plasma cytokine in patients undergoing neoadjuvant androgen deprivation therapy and external beam radiation therapy for adenocarcinoma of the prostate. Ann Transl Med. 2020;8(10):636-636. doi:10.21037/atm-19-1913
  • Wang C, Zhang Y, Gao WQ. The evolving role of immune cells in prostate cancer. Cancer Lett. 2022;525:9-21. doi:10.1016/j.canlet.2021.10.027
There are 32 citations in total.

Details

Primary Language English
Subjects Urology
Journal Section Research Article
Authors

Andy Zulfiqqar 0000-0001-5191-5428

Indrawarman Soerohardjo 0000-0002-1224-0568

Ahmad Zulfan Hendri 0000-0003-3759-8475

Didik Setyo Heriyanto 0000-0001-9728-5046

Publication Date September 30, 2024
Submission Date October 4, 2023
Acceptance Date April 2, 2024
Published in Issue Year 2024 Volume: 41 Issue: 3

Cite

APA Zulfiqqar, A., Soerohardjo, I., Zulfan Hendri, A., Setyo Heriyanto, D. (2024). Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?. Journal of Experimental and Clinical Medicine, 41(3), 474-478.
AMA Zulfiqqar A, Soerohardjo I, Zulfan Hendri A, Setyo Heriyanto D. Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?. J. Exp. Clin. Med. September 2024;41(3):474-478.
Chicago Zulfiqqar, Andy, Indrawarman Soerohardjo, Ahmad Zulfan Hendri, and Didik Setyo Heriyanto. “Can PD-1 Expression in Prostate Cancer Help to Predict Response to Single ADT in an Indonesian Population?”. Journal of Experimental and Clinical Medicine 41, no. 3 (September 2024): 474-78.
EndNote Zulfiqqar A, Soerohardjo I, Zulfan Hendri A, Setyo Heriyanto D (September 1, 2024) Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?. Journal of Experimental and Clinical Medicine 41 3 474–478.
IEEE A. Zulfiqqar, I. Soerohardjo, A. Zulfan Hendri, and D. Setyo Heriyanto, “Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?”, J. Exp. Clin. Med., vol. 41, no. 3, pp. 474–478, 2024.
ISNAD Zulfiqqar, Andy et al. “Can PD-1 Expression in Prostate Cancer Help to Predict Response to Single ADT in an Indonesian Population?”. Journal of Experimental and Clinical Medicine 41/3 (September 2024), 474-478.
JAMA Zulfiqqar A, Soerohardjo I, Zulfan Hendri A, Setyo Heriyanto D. Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?. J. Exp. Clin. Med. 2024;41:474–478.
MLA Zulfiqqar, Andy et al. “Can PD-1 Expression in Prostate Cancer Help to Predict Response to Single ADT in an Indonesian Population?”. Journal of Experimental and Clinical Medicine, vol. 41, no. 3, 2024, pp. 474-8.
Vancouver Zulfiqqar A, Soerohardjo I, Zulfan Hendri A, Setyo Heriyanto D. Can PD-1 expression in prostate cancer help to predict response to single ADT in an Indonesian population?. J. Exp. Clin. Med. 2024;41(3):474-8.