{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T20:09:31Z","timestamp":1779134971521,"version":"3.51.4"},"reference-count":37,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T00:00:00Z","timestamp":1748995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Introduction: Prostate cancer with spinal metastases (PCSM) is associated with high morbidity and mortality. The impact of biomarkers on the prognosis of spinal metastases, however, remains unclear. Objective: This study explored associations between potential biomarkers, treatment modalities, survival, and neurological outcomes in PCSM patients. Methods: We conducted a retrospective analysis of 68 patients as part of a neurosurgical cohort with PCSM at a comprehensive cancer center from 2013 to 2023, examining the influence of potential biomarkers, treatment modalities, and demographics on prognosis. The primary outcomes were the identification of biomarkers, overall survival (OS) in years, survival after spinal metastasis in years, spinal metastasis recurrence, and postoperative neurological outcomes via Frankel scores. Results: All the patients (n = 68) had adenocarcinoma, and the median age was 69 years. The mortality rate was 66% with a median OS of 6 years. Seventy-two biomarkers were identified. An accelerated failure time model (AFT) showed that radiotherapy to the prostate increased the OS (TR = 1.805, p = 0.001), while smoking status (TR = 0.625, p &lt; 0.001) and PTEN gene mutations (TR = 0.504, p = 0.006) were associated with decreased OS. Kaplan\u2013Meier analysis associated PTEN mutations with reduced median OS using the Gehan\u2013Breslow\u2013Wilcoxon test (3.50 vs. 9.49 years; p = 0.001). PTEN mutations were trending towards but were not significant for decreased survival following spinal metastases (2.04 vs. 3.15 years; p = 0.08). Both PTEN (p = 0.02) and Tumor Protein 53 (TP53, p = 0.01) mutations were associated with increased spinal metastasis recurrence when analyzed using Fisher\u2019s exact test. No differences were observed in the median OS or survival after spinal metastases among patients with or without androgen receptor splice variant-7 (AR-V7), prostate-specific membrane antigen (PSMA), TP53, or other analyzed biomarkers. Similarly, neither age, receipt of chemotherapy, nor radiotherapy to the spine correlated with OS. Only chemotherapy was associated with a decreased postoperative Frankel Score (p = 0.002). Conclusions: PTEN mutations and smoking status were associated with decreased OS in patients with PCSM. Both PTEN and TP53 mutations were associated with increased spinal metastasis recurrence. Receipt of radiotherapy to the prostate was correlated with prolonged survival, whereas receipt of radiotherapy to the spine was not. Chemotherapy was associated with decreased postoperative neurological outcomes.<\/jats:p>","DOI":"10.3390\/curroncol32060331","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T03:57:34Z","timestamp":1749009454000},"page":"331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PTEN Mutations Associated with Increased Recurrence and Decreased Survival in Patients with Prostate Cancer Spinal Metastasis"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3169-8873","authenticated-orcid":false,"given":"Albert","family":"Antar","sequence":"first","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6152-8392","authenticated-orcid":false,"given":"Yuanxuan","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4713-8536","authenticated-orcid":false,"given":"Abdel-Hameed","family":"Al-Mistarehi","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pritika","family":"Papali","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie","family":"Alfonzo Horowitz","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreya","family":"Sriram","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shahab Aldin","family":"Sattari","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2057-8419","authenticated-orcid":false,"given":"Carly","family":"Weber-Levine","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9561-8688","authenticated-orcid":false,"given":"Sushanth","family":"Neerumalla","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4971-295X","authenticated-orcid":false,"given":"Benjamin Z.","family":"Mendelson","sequence":"additional","affiliation":[{"name":"School of Medicine, West Virginia University, Morgantown, WV 26506, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5942-8309","authenticated-orcid":false,"given":"Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin J.","family":"Redmond","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Bydon","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy F.","family":"Witham","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5355-2683","authenticated-orcid":false,"given":"Nicholas","family":"Theodore","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9403-9509","authenticated-orcid":false,"given":"Daniel","family":"Lubelski","sequence":"additional","affiliation":[{"name":"School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"ref_1","unstructured":"Leslie, S.W., Soon-Sutton, T.L., Sajjad, H., and Skelton, W.P. (2024). Prostate Cancer. StatPearls, StatPearls Publishing. Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK470550\/."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Kadeerhan, G., Xue, B., Wu, X.-L., Chen, W.-N., and Wang, D.-W. (2023). Incidence trends and survival of metastatic prostate cancer with bone and visceral involvement: 2010-2019 surveillance, epidemiology, and end results. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1201753"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2791","DOI":"10.1007\/s00586-020-06647-6","article-title":"Surgical complications and re-operation rates in spinal metastases surgery: A systematic review","volume":"30","author":"Tarawneh","year":"2020","journal-title":"Eur. Spine J."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/s00586-012-2534-2","article-title":"Surgery and survival outcomes of 22 patients with epidural spinal cord compression caused by thyroid tumor spinal metastases","volume":"22","author":"Zhang","year":"2012","journal-title":"Eur. Spine J."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Alvarez-Cubero, M.J., Arance, E., de Santiago, E., Sanchez, P., Sep\u00falveda, M.R., Marrero, R., Lorente, J.A., Gonzalez-Cabezuelo, J.M., Cuenca-Lopez, S., and Cozar, J.M. (2022). Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010547"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-020-00243-0","article-title":"Prostate cancer","volume":"7","author":"Rebello","year":"2021","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"312","DOI":"10.3892\/ol.2022.13432","article-title":"KIF11: A potential prognostic biomarker for predicting bone metastasis-free survival of prostate cancer","volume":"24","author":"Wang","year":"2022","journal-title":"Oncol. Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.eururo.2016.07.033","article-title":"Subgroups of Castration-resistant Prostate Cancer Bone Metastases Defined Through an Inverse Relationship Between Androgen Receptor Activity and Immune Response","volume":"71","author":"Ylitalo","year":"2017","journal-title":"Eur. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/sc.1969.30","article-title":"The value of postural reduction in the initial management of closed injuries of the spine with paraplegia and tetraplegia","volume":"7","author":"Frankel","year":"1969","journal-title":"Spinal Cord."},{"key":"ref_10","first-page":"a033688","article-title":"Metastases in Prostate Cancer. Cold Spring Harb","volume":"9","author":"Karkampouna","year":"2018","journal-title":"Perspect. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/sj.bjc.6603924","article-title":"FISH analysis of 107 prostate cancers shows that PTEN genomic deletion is associated with poor clinical outcome","volume":"97","author":"Yoshimoto","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/j.eururo.2014.10.027","article-title":"PTEN Protein Loss and Clinical Outcome from Castration-resistant Prostate Cancer Treated with Abiraterone Acetate","volume":"67","author":"Ferraldeschi","year":"2015","journal-title":"Eur. Urol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"50","DOI":"10.4103\/aja.aja_39_21","article-title":"Prognostic value of PTEN in de novo diagnosed metastatic prostate cancer","volume":"24","author":"Zhang","year":"2022","journal-title":"Asian J. Androl."},{"key":"ref_14","first-page":"265","article-title":"Androgen Receptor Splice Variants in the Era of Enzalutamide and Abiraterone","volume":"5","author":"Nakazawa","year":"2014","journal-title":"Discov. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1056\/NEJMoa1315815","article-title":"AR-V7 and Resistance to Enzalutamide and Abiraterone in Prostate Cancer","volume":"371","author":"Antonarakis","year":"2014","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/S0090-4295(98)00278-7","article-title":"Prostate-specific membrane antigen expression is greatest in prostate adenocarcinoma and lymph node metastases","volume":"52","author":"Sweat","year":"1998","journal-title":"Urology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.humpath.2006.11.012","article-title":"Prostate-specific membrane antigen expression as a predictor of prostate cancer progression","volume":"38","author":"Perner","year":"2007","journal-title":"Hum. Pathol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"405","DOI":"10.2967\/jnumed.119.230318","article-title":"Total-Body 68Ga-PSMA-11 PET\/CT for Bone Metastasis Detection in Prostate Cancer Patients: Potential Impact on Bone Scan Guidelines","volume":"61","author":"Pomykala","year":"2020","journal-title":"J. Nucl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Zhou, J., Lai, Y., Peng, S., Tang, C., Chen, Y., Li, L., Huang, H., and Guo, Z. (2022). Comprehensive analysis of TP53 and SPOP mutations and their impact on survival in metastatic prostate cancer. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.957404"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1038\/nrurol.2015.25","article-title":"Radiotherapy for high-risk prostate cancer","volume":"12","author":"Mohiuddin","year":"2015","journal-title":"Nat. Rev. Urol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1016\/j.ijrobp.2007.11.066","article-title":"Long-term results of conformal radiotherapy for prostate cancer: Impact of dose escala-tion on biochemical tumor control and distant metastases-free survival outcomes","volume":"71","author":"Zelefsky","year":"2008","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.1002\/cam4.1655","article-title":"Palliative radiation therapy (RT) for prostate cancer patients with bone metastases at diagnosis: A hospital-based analysis of patterns of care, RT fractionation scheme, and overall survival","volume":"7","author":"Baumann","year":"2018","journal-title":"Cancer Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1227\/neu.0000000000001909","article-title":"Spine Stereotactic Body Radiotherapy for Prostate Cancer Metastases and the Impact of Hormone Sensitivity Status on Local Control","volume":"90","author":"Abugharib","year":"2022","journal-title":"Neurosurgery"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5560","DOI":"10.3390\/curroncol30060420","article-title":"Factors Associated with Long-Term Prostate Cancer Survival after Palliative Radiother-apy to a Bone Metastasis and Contemporary Palliative Systemic Therapy: A Retrospective, Population-Based Study","volume":"30","author":"Venugopal","year":"2023","journal-title":"Curr Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"221","DOI":"10.4103\/aja.aja_40_17","article-title":"Role of chemotherapy in prostate cancer","volume":"20","author":"Nader","year":"2018","journal-title":"Asian J. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.eururo.2015.11.005","article-title":"Androgen Deprivation Therapy (ADT) Plus Docetaxel Versus ADT Alone in Metastatic Non castrate Prostate Cancer: Impact of Metastatic Burden and Long-term Survival Analysis of the Randomized Phase 3 GETUG-AFU15 Trial","volume":"70","author":"Gravis","year":"2016","journal-title":"Eur. Urol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1016\/S0140-6736(15)01037-5","article-title":"Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial","volume":"387","author":"James","year":"2016","journal-title":"Lancet"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1080\/14712598.2022.2027904","article-title":"Prostate cancer immunotherapy","volume":"22","author":"Mitsogiannis","year":"2022","journal-title":"Expert. Opin. Biol. Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1056\/NEJMoa1001294","article-title":"Sipuleucel-T Immunotherapy for Castration-Resistant Prostate Cancer","volume":"363","author":"Kantoff","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_31","unstructured":"(2021). Prostate Cancer. Version 2. **Important Practical Guidelines for PCa Treatment from the Oncologist Perspective. NCCN Clinical Practive Guidelines in Oncology (NCCN Guidelines), NCCN."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.1016\/j.ijrobp.2010.07.2004","article-title":"Older age predicts decreased metastasis and prostate cancer-specific death for men treated with radiation therapy: Meta-analysis of radiation therapy oncology group trials","volume":"81","author":"Hamstra","year":"2011","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_33","first-page":"3","article-title":"Research recommendations for radiation therapy in older cancer patients. Report from the National Institute on Aging, National Cancer Institute, and American College of Radiology Workshop: Radiation therapy and cancer in older persons","volume":"43","author":"Yancik","year":"1999","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1001\/jamaoncol.2018.1071","article-title":"Association of Smoking Status With Recurrence, Metastasis, and Mortality Among Pa-tients With Localized Prostate Cancer Undergoing Prostatectomy or Radiotherapy: A Systematic Review and Meta-analysis","volume":"4","author":"Foerster","year":"2018","journal-title":"JAMA Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2548","DOI":"10.1001\/jama.2011.879","article-title":"Smoking and prostate cancer survival and recurrence","volume":"305","author":"Kenfield","year":"2011","journal-title":"JAMA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.canep.2010.06.017","article-title":"Cancer screening behaviors among smokers and non-smokers","volume":"34","author":"Byrne","year":"2010","journal-title":"Cancer Epidemiol."},{"key":"ref_37","first-page":"604","article-title":"Cigarette smoking and risk of prostate cancer in middle-aged men","volume":"12","author":"Plaskon","year":"2003","journal-title":"Cancer Epidemiol. Biomarkers Prev."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/6\/331\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:46:17Z","timestamp":1760031977000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/32\/6\/331"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,4]]},"references-count":37,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["curroncol32060331"],"URL":"https:\/\/doi.org\/10.3390\/curroncol32060331","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,4]]}}}