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Natural history of untreated prostate cancer: a comprehensive review of long-term progression patterns and survival outcomes

Prostate Cancer and Prostatic Diseases (2026)Cite this article

Subjects

Abstract

Purpose

We systematically reviewed the long-term outcomes of untreated prostate cancer across different risk categories to inform treatment decisions and active surveillance protocols. This comprehensive analysis synthesizes long-term progression data across tumor staging and grading systems.

Materials and methods

We conducted a systematic literature search of PubMed, EMBASE, and Cochrane databases (1990–2025) for studies reporting ≥10-year outcomes in untreated or conservatively managed prostate cancer patients. Eligible studies included observational cohorts, population registries, and meta-analyses. Primary endpoints included prostate cancer-specific mortality, metastatic progression, and competing mortality.

Results

Fifteen major studies encompassing 43,127 patients (median follow-up 15–30 years) demonstrated heterogeneous progression patterns. Ten-year prostate cancer-specific survival ranged from >95% for Gleason 6 tumors to <60% for Gleason 8–10 disease. Grade Group 1 tumors showed <5% metastatic risk over 15–20 years, while Grade Groups 4–5 exhibited rapid progression with median disease-specific survival <5 years. Across all risk groups, disease progression accelerated markedly after 15 years. Men diagnosed after age 75 faced substantial competing mortality (~57–60% 10-year non-cancer mortality), regardless of tumor grade.

Conclusions

Tumor grade is the strongest prognostic factor in the natural history of untreated prostate cancer. Low-grade disease often remains indolent for 15–20 years, whereas high-grade tumors frequently progress to lethal disease within a few years, warranting early intervention. These findings support contemporary active surveillance protocols for low-risk patients and inform evidence-based treatment decisions for higher-risk disease.

Summary with methodological context:

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References

  1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48.

    PubMed  Google Scholar 

  2. Grossman DC, Curry SJ, Owens DK, Bibbins-Domingo K, Caughey AB, Davidson KW, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319:1901–1913.

    Article  PubMed  Google Scholar 

  3. Lu-Yao GL, Yao SL. Population-based study of long-term survival in patients with clinically localised prostate cancer. Lancet. 1997;349:906–910.

    Article  CAS  PubMed  Google Scholar 

  4. Klotz L. Active surveillance for prostate cancer: patient selection and management. Curr Oncol. 2010;17:S11–S17.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Dall’Era MA, Albertsen PC, Bangma C, Carroll PR, Carter HB, Cooperberg MR, et al. Active surveillance for prostate cancer: a systematic review of the literature. Eur Urol. 2012;62:976–983.

    Article  PubMed  Google Scholar 

  6. Bruinsma SM, Bangma CH, Carroll PR, Leapman ML, Rannikko A, Petrides V, et al. Active surveillance for prostate cancer: a narrative review of clinical guidelines. Nat Rev Urol. 2016;13:151–167.

    Article  CAS  PubMed  Google Scholar 

  7. Johansson JE, Holmberg L, Johansson S, Bergström R, Adami HO. Fifteen-year survival in prostate cancer: a prospective, population-based study in Sweden. JAMA. 1997;277:467–471.

    Article  CAS  PubMed  Google Scholar 

  8. Albertsen PC, Hanley JA, Fine J. 20-year outcomes following conservative management of clinically localized prostate cancer. JAMA. 2005;293:2095–2101.

    Article  CAS  PubMed  Google Scholar 

  9. Lu-Yao GL, Albertsen PC, Moore DF, Shih W, Lin Y, DiPaola RS, et al. Outcomes of localized prostate cancer following conservative management. JAMA. 2009;302:1202–1209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bill-Axelson A, Holmberg L, Garmo H, Rider JR, Taari K, Busch C, et al. Radical prostatectomy or watchful waiting in early prostate cancer. N Engl J Med. 2014;370:932–942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Holmberg L, Bill-Axelson A, Helgesen F, Salo JO, Folmerz P, Häggman M, et al. A randomized trial comparing radical prostatectomy with watchful waiting in early prostate cancer. N Engl J Med. 2002;347:781–789.

    Article  PubMed  Google Scholar 

  12. Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017;377:132–142.

    Article  PubMed  Google Scholar 

  13. Klotz L, Vesprini D, Sethukavalan P, Jethava V, Zhang L, Jain S, et al. Long-term follow-up of a large active surveillance cohort of patients with prostate cancer. J Clin Oncol. 2015;33:272–277.

    Article  PubMed  Google Scholar 

  14. Cooperberg MR, Carroll PR, Klotz L. Active surveillance for prostate cancer: progress and promise. J Clin Oncol. 2011;29:3669–3676.

    Article  PubMed  Google Scholar 

  15. Adolfsson J, Steineck G, Whitmore WF Jr. Recent results of management of palpable clinically localized prostate cancer. Cancer. 1993;72:310–322.

    Article  CAS  PubMed  Google Scholar 

  16. Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score ≤6 have the potential to metastasize to lymph nodes? Am J Surg Pathol. 2012;36:1346–1352.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sakr WA, Tefilli MV, Grignon DJ, Banerjee M, Dey J, Gheiler EL, et al. Gleason score 7 prostate cancer: a heterogeneous entity? Correlation with pathologic parameters and disease-free survival. Urology. 2000;56:730–734.

    Article  CAS  PubMed  Google Scholar 

  18. D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med. 2004;351:125–135.

    Article  PubMed  Google Scholar 

  19. Draisma G, Etzioni R, Tsodikov A, Mariotto A, Wever E, Gulati R, et al. Lead time and overdiagnosis in prostate-specific antigen screening: importance of methods and context. J Natl Cancer Inst. 2009;101:374–383.

    Article  PubMed  PubMed Central  Google Scholar 

  20. D’Amico AV, Whittington R, Malkowicz SB, Schultz D, Blank K, Broderick GA, et al. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280:969–974.

    Article  PubMed  Google Scholar 

  21. Carter HB, Ferrucci L, Kettermann A, Landis P, Wright CH, Epstein JI, et al. Detection of life-threatening prostate cancer with prostate-specific antigen velocity during a window of curability. J Natl Cancer Inst. 2006;98:1521–1527.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Popiolek M, Rider JR, Andrén O, Andersson SO, Holmberg L, Adami HO, et al. Natural history of early, localized prostate cancer: a final report from three decades of follow-up. Eur Urol. 2013;63:428–435.

    Article  PubMed  Google Scholar 

  23. Daskivich TJ, Chamie K, Kwan L, Labo J, Dash A, Greenfield S, et al. Comorbidity and competing risks for mortality in men with prostate cancer. Cancer. 2011;117:4642–4650.

    Article  PubMed  Google Scholar 

  24. Chodak GW, Thisted RA, Gerber GS, Johansson JE, Adolfsson J, Jones GW, et al. Results of conservative management of clinically localized prostate cancer. N Engl J Med. 1994;330:242–248.

    Article  CAS  PubMed  Google Scholar 

  25. Hamdy FC, Donovan JL, Lane JA, Mason M, Metcalfe C, Holding P, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375:1415–1424.

    Article  PubMed  Google Scholar 

  26. Schröder FH, Hugosson J, Roobol MJ, Tammela TL, Ciatto S, Nelen V, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360:1320–1328.

    Article  PubMed  Google Scholar 

  27. Rosato R, De Luca S, Zitella A, Munoz F, Baima CG, Barale M, et al. Quality of life in low-risk prostate cancer under active surveillance or following radical treatments: the START cohort study. Prostate Cancer Prostatic Dis. 2025. https://doi.org/10.1038/s41391-025-01032-0.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Desmond C, Kaul S, Fleishman A, Korets R, Chang P, Wagner A, et al. The association of patient and disease characteristics with the overtreatment of low-risk prostate cancer from 2010 to 2016. Prostate Cancer Prostatic Dis. 2025;28:385–393.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Icahn School of Medicine At Mount Sinai, New York, NY, USA

    Ashutosh. K. Tewari, Reza Mehrazin, Peter Wiklund, Micheal DeMeo, Steven A. Kaplan & Alexis E. Te

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  1. Ashutosh. K. Tewari
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  2. Reza Mehrazin
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  3. Peter Wiklund
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  4. Micheal DeMeo
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  6. Alexis E. Te
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Contributions

AET – Concept Development, drafting and revising the manuscript, and communication as the corresponding author. AKT - Concept Development, supervising the project, and critically reviewing the manuscript. MD – Assist in drafting, reviewing and editing the manuscript. RM - Critically reviewing and editing the manuscript. SAK - Critically reviewing and editing the manuscript. PW - Critically reviewing and editing the manuscript.

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Correspondence to Alexis E. Te.

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Tewari, A.K., Mehrazin, R., Wiklund, P. et al. Natural history of untreated prostate cancer: a comprehensive review of long-term progression patterns and survival outcomes. Prostate Cancer Prostatic Dis (2026). https://doi.org/10.1038/s41391-026-01095-7

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