Clinical Predictors and Risk Factors of Gleason Score Upgrade: A Retrospective Cohort Analysis
Abstract
:1. Introduction
2. Patients and Methods
2.1. Overall Study Design
2.2. Statistical Analysis
3. Results
3.1. Study Population
3.2. Univariable Predictors of Gleason Upgrade
3.3. Multivariable Analysis
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Mirone, V.; Imbimbo, C.; Arcaniolo, D.; Franco, M.; La Rocca, R.; Venturino, L.; Spirito, L.; Creta, M.; Verze, P. Knowledge, attitudes, and practices towards prostate cancer screening amongst men living in the southern Italian peninsula: The Prevention and Research in Oncology (PRO) non-profit Foundation experience. World J. Urol. 2017, 35, 1857–1862. [Google Scholar] [CrossRef] [PubMed]
- Crocetto, F.; Barone, B.; Caputo, V.F.; Fontana, M.; de Cobelli, O.; Ferro, M. BRCA Germline Mutations in Prostate Cancer: The Future Is Tailored. Diagnostics 2021, 11, 908. [Google Scholar] [CrossRef] [PubMed]
- Catalona, W.J.; Bigg, S.W. Nerve-sparing radical prostatectomy: Evaluation of results after 250 patients. J. Urol. 1990, 143, 538–543; discussion 544. [Google Scholar] [CrossRef]
- Anguas-Gracia, A.; Antón-Solanas, I.; Echániz-Serrano, E.; Subirón-Valera, A.B.; Rodríguez-Roca, B.; Juárez-Vela, R.; Satustegui-Dordá, P.J.; Fernández-Rodríguez, M.T.; Gea-Caballero, V.; Tejada-Garrido, C.I.; et al. Quality of Life after Radical Prostatectomy: A Longitudinal Study. Nurs. Rep. 2023, 13, 1051–1063. [Google Scholar] [CrossRef] [PubMed]
- Klein, E.A.; Bianco, F.J.; Serio, A.M.; Eastham, J.A.; Kattan, M.W.; Pontes, J.E.; Vickers, A.J.; Scardino, P.T. Surgeon Experience is Strongly Associated with Biochemical Recurrence after Radical Prostatectomy for all Preoperative Risk Categories. J. Urol. 2008, 179, 2212–2217. [Google Scholar] [CrossRef]
- Epstein, J.I.; Egevad, L.; Amin, M.B.; Delahunt, B.; Srigley, J.R.; Humphrey, P.A. Grading Committee the 2014 International Society of Urological Pathology (ISUP) Consensus Conference on Gleason Grading of Prostatic Carcinoma: Definition of Grading Patterns and Proposal for a New Grading System. Am. J. Surg. Pathol. 2016, 40, 244–252. [Google Scholar] [CrossRef]
- Loeb, S.; Folkvaljon, Y.; Robinson, D.; Lissbrant, I.F.; Egevad, L.; Stattin, P. Evaluation of the 2015 Gleason Grade Groups in a Nationwide Population-based Cohort. Eur. Urol. 2016, 69, 1135–1141. [Google Scholar] [CrossRef]
- Gentile, F.; La Civita, E.; Ventura, B.D.; Ferro, M.; Bruzzese, D.; Crocetto, F.; Tennstedt, P.; Steuber, T.; Velotta, R.; Terracciano, D. A Neural Network Model Combining [-2]proPSA, freePSA, Total PSA, Cathepsin D, and Thrombospondin-1 Showed Increased Accuracy in the Identification of Clinically Significant Prostate Cancer. Cancers 2023, 15, 1355. [Google Scholar] [CrossRef]
- Hao, S.; Wang, H.; Lin, S.; Chen, H.; Xie, L.; Zheng, X. Analysis of risk factors for persistent PSA after radical prostatectomy: Results from a high-volume center in Southeast China. BMC Urol. 2024, 24, 185. [Google Scholar] [CrossRef]
- Komori, T.; Matsumoto, K.; Kosaka, T.; Takeda, T.; Kamitani, R.; Yasumizu, Y.; Tanaka, N.; Morita, S.; Mizuno, R.; Asanuma, H.; et al. Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy. Ann. Surg. Oncol. 2023, 30, 6936–6942. [Google Scholar] [CrossRef]
- Barone, B.; Amicuzi, U.; Massanova, M.; Napolitano, L.; Reccia, P.; Mirto, B.F.; Balsamo, R.; Giudice, F.D.; Ferro, M.; Busetto, G.M.; et al. The Correlation Between Body Mass Index and Prostate Volume: A Retrospective Analysis of Pre and Postoperative Measurements in Prostate Cancer Patients. Prostate 2024, 85, 433–442. [Google Scholar] [CrossRef] [PubMed]
- Dickerman, B.A.; Ahearn, T.U.; Giovannucci, E.; Stampfer, M.J.; Nguyen, P.L.; Mucci, L.A.; Wilson, K.M. Weight change, obesity, and risk of prostate cancer progression among men with clinically localized prostate cancer. Int. J. Cancer 2017, 141, 933–944. [Google Scholar] [CrossRef]
- Lucia, M.S.; Epstein, J.I.; Goodman, P.J.; Darke, A.K.; Reuter, V.E.; Civantos, F.; Tangen, C.M.; Parnes, H.L.; Lippman, S.M.; La Rosa, F.G.; et al. Finasteride and high-grade prostate cancer in the Prostate Cancer Prevention Trial. J. Natl. Cancer Inst. 2007, 99, 1375–1383. [Google Scholar] [CrossRef] [PubMed]
- Heidenreich, A.; Bellmunt, J.; Bolla, M.; Joniau, S.; Mason, M.; Matveev, V.; Mottet, N.; Schmid, H.-P.; van der Kwast, T.; Wiegel, T.; et al. EAU guidelines on prostate cancer. Part 1: Screening, diagnosis, and treatment of clinically localised disease. Eur. Urol. 2011, 59, 61–71. [Google Scholar] [CrossRef] [PubMed]
- Heidenreich, A.; Bastian, P.J.; Bellmunt, J.; Bolla, M.; Joniau, S.; van der Kwast, T.; Mason, M.; Matveev, V.; Wiegel, T.; Zattoni, F.; et al. EAU guidelines on prostate cancer. part 1: Screening, diagnosis, and local treatment with curative intent-update 2013. Eur. Urol. 2014, 65, 124–137. [Google Scholar] [CrossRef]
- Stabile, A.; Giganti, F.; Rosenkrantz, A.B.; Taneja, S.S.; Villeirs, G.; Gill, I.S.; Allen, C.; Emberton, M.; Moore, C.M.; Kasivisvanathan, V. Multiparametric MRI for prostate cancer diagnosis: Current status and future directions. Nat. Rev. Urol. 2020, 17, 41–61. [Google Scholar] [CrossRef]
- Rapisarda, S.; Bada, M.; Crocetto, F.; Barone, B.; Arcaniolo, D.; Polara, A.; Imbimbo, C.; Grosso, G. The role of multiparametric resonance and biopsy in prostate cancer detection: Comparison with definitive histological report after laparoscopic/robotic radical prostatectomy. Abdom. Radiol. 2020, 45, 4178–4184. [Google Scholar] [CrossRef]
- Houshmand, S.; Lawhn-Heath, C.; Behr, S. PSMA PET imaging in the diagnosis and management of prostate cancer. Abdom. Radiol. 2023, 48, 3610–3623. [Google Scholar] [CrossRef]
- Borchers, H.; Brehmer, B.; Kirschner-Hermanns, R.; Reineke, T.; Tietze, L.; Jakse, G. Erectile function after non-nerve-sparing radical prostatectomy: Fact or fiction? Urol. Int. 2006, 76, 213–216. [Google Scholar] [CrossRef]
- Krishnan, R.; Katz, D.; Nelson, C.J.; Mulhall, J.P. Erectile function recovery in patients after non-nerve sparing radical prostatectomy. Andrology 2014, 2, 951–954. [Google Scholar] [CrossRef]
- Kyriazis, I.; Spinos, T.; Tsaturyan, A.; Kallidonis, P.; Stolzenburg, J.U.; Liatsikos, E. Different Nerve-Sparing Techniques during Radical Prostatectomy and Their Impact on Functional Outcomes. Cancers 2022, 14, 1601. [Google Scholar] [CrossRef]
- Michl, U.; Tennstedt, P.; Feldmeier, L.; Mandel, P.; Oh, S.J.; Ahyai, S.; Budäus, L.; Chun, F.K.H.; Haese, A.; Heinzer, H.; et al. Nerve-sparing Surgery Technique, Not the Preservation of the Neurovascular Bundles, Leads to Improved Long-term Continence Rates After Radical Prostatectomy. Eur. Urol. 2016, 69, 584–589. [Google Scholar] [CrossRef]
- Keller, E.X.; Bachofner, J.; Britschgi, A.J.; Saba, K.; Mortezavi, A.; Kaufmann, B.; Fankhauser, C.D.; Wild, P.; Sulser, T.; Hermanns, T.; et al. Prognostic value of unifocal and multifocal positive surgical margins in a large series of robot-assisted radical prostatectomy for prostate cancer. World J. Urol. 2019, 37, 1837–1844. [Google Scholar] [CrossRef] [PubMed]
- Sivathasan, S.; Patel, K.M.; Smart, S.; Nathan, A.; Warren, A.; Shah, N.; Lamb, B.W. Incremental modification of robotic prostatectomy technique can lead to aggregated marginal gains to significantly improve functional outcomes without compromising oncological control. J. Robot. Surg. 2022, 16, 665–675. [Google Scholar] [CrossRef] [PubMed]
- Soeterik, T.F.W.; van Melick, H.H.E.; Dijksman, L.M.; Stomps, S.; Witjes, J.A.; van Basten, J.P.A. Nerve Sparing during Robot-Assisted Radical Prostatectomy Increases the Risk of Ipsilateral Positive Surgical Margins. J. Urol. 2020, 204, 91–95. [Google Scholar] [CrossRef]
- Spirito, L.; Chessa, F.; Hagman, A.; Lantz, A.; Celentano, G.; Sanchez-Salas, R.; La Rocca, R.; Olsson, M.; Akre, O.; Mirone, V.; et al. Long-Term Oncological Outcomes after Nerve-Sparing Robot-Assisted Radical Prostatectomy for High-Risk Localized Prostate Cancer: A Single-Center, Two-Arm Prospective Study. Diagnostics 2024, 14, 803. [Google Scholar] [CrossRef] [PubMed]
- Grossi, F.S.; Utano, E.; Minafra, P.; Prontera, P.P.; Schiralli, F.; De Cillis, A.; Martinelli, E.; Lattarulo, M.; Luka, M.; Carrieri, A.; et al. Oncological and functional outcomes of extraperitoneal laparoscopic radical prostatectomy: An 18-years, single-center experience. Arch. Ital. Urol. Androl. 2021, 93, 268–273. [Google Scholar] [CrossRef]
- Carver, B.S.; Kattan, M.W.; Scardino, P.T.; Eastham, J.A. Gleason grade remains an important prognostic predictor in men diagnosed with prostate cancer while on finasteride therapy. BJU Int. 2005, 95, 509–512. [Google Scholar] [CrossRef]
- Godtman, R.A.; Kollberg, K.S.; Pihl, C.-G.; Månsson, M.; Hugosson, J. The Association Between Age, Prostate Cancer Risk, and Higher Gleason Score in a Long-term Screening Program: Results from the Göteborg-1 Prostate Cancer Screening Trial. Eur. Urol. 2022, 82, 311–317. [Google Scholar] [CrossRef]
- Gravina, M.; Spirito, L.; Celentano, G.; Capece, M.; Creta, M.; Califano, G.; Collà Ruvolo, C.; Morra, S.; Imbriaco, M.; Di Bello, F.; et al. Machine Learning and Clinical-Radiological Characteristics for the Classification of Prostate Cancer in PI-RADS 3 Lesions. Diagnostics 2022, 12, 1565. [Google Scholar] [CrossRef]
- Pinsky, P.; Parnes, H.; Ford, L. Estimating rates of true high-grade disease in the prostate cancer prevention trial. Cancer Prev. Res. (Phila) 2008, 1, 182–186. [Google Scholar] [CrossRef] [PubMed]
- Tarle, M.; Spajic, B.; Kraljic, I.; Kusic, Z. Continuous finasteride therapy for benign prostate hypertrophy upgrades both neuroendorcine differentiation and aggressive prostate cancer. Anticancer Res. 2009, 29, 1797–1801. [Google Scholar] [PubMed]
- Barqawi, A.B.; O’Donnell, C.I.; Siomos, V.J.; Hou, A.H. The effect of short-term dutasteride intake in early-stage prostate cancer: Analysis of 148 patients who underwent three-dimensional prostate mapping biopsy. Urology 2010, 76, 1067–1071. [Google Scholar] [CrossRef] [PubMed]
- Dai, C.; Ganesan, V.; Zabell, J.; Nyame, Y.A.; Almassi, N.; Greene, D.J.; Hettel, D.; Reichard, C.; Haywood, S.C.; Arora, H.; et al. Impact of 5α-Reductase Inhibitors on Disease Reclassification among Men on Active Surveillance for Localized Prostate Cancer with Favorable Features. J. Urol. 2018, 199, 445–452. [Google Scholar] [CrossRef]
- Herden, J.; Heidenreich, A.; Wittekind, C.; Weissbach, L. Predictive value of the UICC and AJCC 8th edition tumor-nodes-metastasis (TNM) classification for patients treated with radical prostatectomy. Cancer Epidemiol. 2018, 56, 126–132. [Google Scholar] [CrossRef]
- Potter, S.R.; Epstein, J.I.; Partin, A.W. Seminal Vesicle Invasion by Prostate Cancer: Prognostic Significance and Therapeutic Implications. Rev. Urol. 2000, 2, 190–195. [Google Scholar]
- Massanova, M.; Barone, B.; Caputo, V.; Napolitano, L.; Ponsiglione, A.; Del Giudice, F.; Ferro, M.; Lucarelli, G.; Lasorsa, F.; Busetto, G.; et al. The detection rate for prostate cancer in systematic and targeted prostate biopsy in biopsy-naive patients, according to the localization of the lesion at the mpMRI: A single-center retrospective observational study. Prostate 2024, 84, 1234–1243. [Google Scholar] [CrossRef]
- Ponsiglione, A.; Stanzione, A.; Minieri, A.; Musella, R.; D’Elia, A.C.; Negroni, D.; Sacco, M.; Brancaccio, D.; Sicignano, E.; Muto, F.; et al. Impact of software-assisted structured reporting on radiology residents approaching prostate MRI. Eur. J. Radiol. 2024, 183, 111889. [Google Scholar] [CrossRef]
- Marks, L.; Young, S.; Natarajan, S. MRI–ultrasound fusion for guidance of targeted prostate biopsy. Curr. Opin. Urol. 2013, 23, 43–50. [Google Scholar] [CrossRef]
- Spirito, L.; Marra, A.; Mirone, V.; Manfredi, C.; Fusco, F.; Napolitano, L.; Servillo, G.; Logrieco, N.; Buonanno, P. Role of spinal anesthesia in robot-assisted radical prostatectomy: Gamble or opportunity? Arch. Ital. Urol. Androl. 2023, 95, 11311. [Google Scholar] [CrossRef]
- Mazzone, E.; Gandaglia, G.; Ploussard, G.; Marra, G.; Valerio, M.; Campi, R.; Mari, A.; Minervini, A.; Serni, S.; Moschini, M.; et al. Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups. Eur. Urol. 2022, 81, 193–203. [Google Scholar] [CrossRef] [PubMed]
- Romano, L.; Napolitano, L.; Crocetto, F.; Sciorio, C.; Sio, M.D.; Miranda, A.; Romano, M.; Priadko, K. Prostate and gut: Any relationship? A narrative review on the available evidence and putative mechanisms. Prostate 2024, 84, 513–524. [Google Scholar] [CrossRef] [PubMed]
- Gelikman, D.G.; Azar, W.S.; Yilmaz, E.C.; Lin, Y.; Shumaker, L.A.; Fang, A.M.; Harmon, S.A.; Huang, E.P.; Parikh, S.H.; Hyman, J.A.; et al. A Prostate Imaging-Reporting and Data System version 2.1-based predictive model for clinically significant prostate cancer diagnosis. BJU Int. 2024, 135, 751–759. [Google Scholar] [CrossRef] [PubMed]
Variable | Available Data Count |
---|---|
Preoperative PSA | 779 |
Age | 779 |
Tumor length | 706 |
Prostate weight | 300 |
pT (pathological T stage) | 779 |
Alpha (5-alpha reductase inhibitor use or not) | 779 |
Lymph node positivity | 411 |
Gleason Upgrade Status | Count | Percentage (%) |
---|---|---|
No Upgrade | 533 | 68.42 |
Upgrade | 246 | 31.58 |
Variable | No Upgrade Median (n) | Upgrade Median (n) | p-Value |
---|---|---|---|
Preoperative PSA | 10.00 (533) | 9.35 (246) | 0.12279 |
Age | 64.00 (533) | 63.00 (246) | 0.00364 * |
Tumor length | 12.00 (500) | 7.00 (206) | 0.00002 * |
Prostate weight | 38.00 (246) | 33.50 (54) | 0.11716 |
Variable | Category | No Upgrade n (%) | Upgrade n (%) | p-Value |
---|---|---|---|---|
Pathological T stage (pT) | pT2 | 178 (77.0) | 53 (23.0) | 0.01114 * |
pT3a | 253 (64.4) | 140 (35.6) | ||
pT3b | 96 (64.9) | 52 (35.1) | ||
pT4 | 6 (85.7) | 1 (14.3) | ||
5-alpha reductase inhibitor use | No (0.0) | 488 (69.6) | 213 (30.4) | 0.03932 * |
Yes (1.0) | 45 (57.7) | 33 (42.3) | ||
Lymph node positivity | No | 289 (81.6) | 65 (18.4) | <0.01 * |
Yes | 244 (57.4) | 181 (42.6) |
Variable | Odds Ratio (OR) | 95% CI | p-Value |
---|---|---|---|
Intercept | 2.626 | — | 0.45248 |
(pT3/pT4 vs. pT2) | 2.807 | — | 0.00135 * |
Use of 5-alpha reductase inhibitors (Yes vs. No) | 3.809 | — | 0.00004 * |
Age | 0.951 | — | 0.01101 * |
Tumor length | 0.989 | — | 0.10731 |
Lymph node positivity | 0.950 | — | 0.52735 |
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Sciorio, C.; Giannella, R.; Romano, L.; Mirto, B.F.; Di Girolamo, A.; Ruffo, A.; Romeo, G.; Esposito, F.; Crocetto, F.; Napolitano, L.; et al. Clinical Predictors and Risk Factors of Gleason Score Upgrade: A Retrospective Cohort Analysis. Diagnostics 2025, 15, 1238. https://doi.org/10.3390/diagnostics15101238
Sciorio C, Giannella R, Romano L, Mirto BF, Di Girolamo A, Ruffo A, Romeo G, Esposito F, Crocetto F, Napolitano L, et al. Clinical Predictors and Risk Factors of Gleason Score Upgrade: A Retrospective Cohort Analysis. Diagnostics. 2025; 15(10):1238. https://doi.org/10.3390/diagnostics15101238
Chicago/Turabian StyleSciorio, Carmine, Riccardo Giannella, Lorenzo Romano, Benito Fabio Mirto, Antonio Di Girolamo, Antonio Ruffo, Giuseppe Romeo, Fabio Esposito, Felice Crocetto, Luigi Napolitano, and et al. 2025. "Clinical Predictors and Risk Factors of Gleason Score Upgrade: A Retrospective Cohort Analysis" Diagnostics 15, no. 10: 1238. https://doi.org/10.3390/diagnostics15101238
APA StyleSciorio, C., Giannella, R., Romano, L., Mirto, B. F., Di Girolamo, A., Ruffo, A., Romeo, G., Esposito, F., Crocetto, F., Napolitano, L., Balsamo, R., Trama, F., Bottone, F., Quattrone, C., Imperatore, V., & Spirito, L. (2025). Clinical Predictors and Risk Factors of Gleason Score Upgrade: A Retrospective Cohort Analysis. Diagnostics, 15(10), 1238. https://doi.org/10.3390/diagnostics15101238