BACKGROUND: Patients with nonmetastatic prostate cancer (nmPCa) and high prostate-specific antigen (PSA) levels due to the high likelihood of metastasis pose a clinical dilemma regarding their optimal treatment and long-term outcomes after initial local therapy. We aimed to evaluate the oncologic outcomes of patients treated with radical prostatectomy (RP) or radiotherapy (RT) for nmPCa with high PSA levels. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER) database to identify patients diagnosed with nmPCa who received RP or RT from 2004 through 2015. We included nmPCa patients with high PSA levels categorized as ≥50 and ≥98 ng/mL, the highest level recorded in SEER. We used the Kaplan-Meier method and Cox proportional hazards to analyze cancer-specific (CSS) and overall survival (OS). RESULTS: We included 6177 patients with nmPCa and PSA ≥ 50 ng/mL at diagnosis; 1698 (27%) had PSA ≥ 98 ng/mL. Of these, 1658 (26.8%) underwent RP and 4519 (73.16%) patients received primary RT. Within a median of 113 months (interquartile range 74-150 months), the 5- and 10-year CSS estimates were 92.3% and 81.5% respectively; 10-year OS was 61%. In the PSA ≥ 98 ng/mL subgroup 5- and 10-year CSS estimates were 89.2% and 76%, respectively. In multivariable analyses for CSS, ISUP grade group (p < 0.001), N stage (p < 0.001), treatment with RP (hazard ratio [HR] = 0.60, 95% confidence interval [CI] 0.43-0.83, p < 0.001), and patient's age (p < 0.05) were associated with improved CSS. In the whole cohort of patients with PSA ≥ 50 ng/mL and RP subgroup, PSA failed to retain its independent prognostic value for CSS. CONCLUSIONS: Patients treated with local therapy for nmPCa with very high PSA at diagnosis have relatively good long-term oncological outcomes. Therefore, among well-selected patients with nmPCa, high PSA levels alone should not preclude the use of radical local therapy. Potential selection bias limits inferences about the relative effectiveness of specific local therapies in this setting.

3rd Radiotherapy and Chemotherapy Department Maria Skłodowska Curie National Research Institute of Oncology Warszawa Poland

Cancer Prognostics and Health Outcomes Unit University of Montreal Health Centre Montreal Canada

Department of General Oncological and Functional Urology Medical University of Warsaw Warsaw Poland

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology APHM North Academic Hospital Marseille France

Department of Urology Clinico San Carlos Hospital Madrid Spain

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology Hourani Center for Applied Scientific Research Al Ahliyya Amman University Amman Jordan

Department of Urology Jagiellonian University in Cracow Kraków Poland

Department of Urology La Croix du Sud Hospital Quint Fonsegrives France

Department of Urology Medical University of Silesia Zabrze Poland

Department of Urology The Jikei University School of Medicine Tokyo Japan

Department of Urology University of Texas Southwestern Dallas Texas USA

Department of Urology Yale School of Medicine New Haven Connecticut USA

Division of Experimental Oncology Unit of Urology Urological Research Institute IRCCS Ospedale San Raffaele Milan Italy

Institute for Urology and Reproductive Health Sechenov University Moscow Russia

Karl Landsteiner Institute of Urology and Andrology Vienna Austria

Weill Cornell Medical College New York New York USA

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Schröder FH, Hugosson J, Roobol MJ, et al. Screening and prostate-cancer mortality in a randomized European study. N Engl J Med. 2009;360(13):1320-1328. doi:10.1056/NEJMoa0810084

Cooperberg MR, Broering JM, Carroll PR. Risk assessment for prostate cancer metastasis and mortality at the time of diagnosis. J Natl Cancer Inst. 2009;101(12):878-887. doi:10.1093/jnci/djp122

D'Amico AV. Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer. JAMA. 1998;280(11):969-974. doi:10.1001/jama.280.11.969

Radziszewski P, Ślusarczyk A. Re: 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;82(2):240-241. doi:10.1016/j.eururo.2022.03.019

Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022;72(1):7-33. doi:10.3322/caac.21708

Stattin K, Sandin F, Bratt O, Lambe M. The risk of distant metastases and cancer specific survival in men with serum prostate specific antigen values above 100 ng/ml. J Urol. 2015;194(6):1594-1600. doi:10.1016/j.juro.2015.07.082

Thomsen FB, Westerberg M, Garmo H, et al. Prediction of metastatic prostate cancer by prostate-specific antigen in combination with T stage and gleason grade: nationwide, population-based register study. PLoS One. 2020;15(1):e0228447. doi:10.1371/journal.pone.0228447

Hamdy FC, Donovan JL, Lane JA, et al. 10-year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. N Engl J Med. 2016;375(15):1415-1424. doi:10.1056/NEJMoa1606220

Bruwer G, Heyns CF, Allen FJ. Influence of local tumour stage and grade on reliability of serum prostate-specific antigen in predicting skeletal metastases in patients with adenocarcinoma of the prostate. Eur Urol. 1999;35(3):223-227. doi:10.1159/000019850

Wilt TJ, Jones KM, Barry MJ, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017;377(2):132-142. doi:10.1056/NEJMoa1615869

Parker CC, James ND, Brawley CD, et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet. 2018;392(10162):2353-2366. doi:10.1016/S0140-6736(18)32486-3

Yanagisawa T, Rajwa P, Thibault C, et al. Androgen receptor signaling inhibitors in addition to docetaxel with androgen deprivation therapy for metastatic hormone-sensitive prostate cancer: a systematic review and meta-analysis. Eur Urol. 2022;82(6):584-598. doi:10.1016/j.eururo.2022.08.002

Ang M, Rajcic B, Foreman D, Moretti K, O'Callaghan ME. Men presenting with prostate-specific antigen (PSA) values of over 100 ng/mL. BJU Int. 2016;117(S4):68-75. doi:10.1111/bju.13411

Rana A, Karamanis K, Lucas MG, Chisholm GD. Identification of metastatic disease by T category, gleason score and serum PSA level in patients with carcinoma of the prostate. Br J Urol. 1992;69(3):277-281. doi:10.1111/j.1464-410X.1992.tb15528.x

Hofman MS, Lawrentschuk N, Francis RJ, et al. Prostate-specific membrane antigen PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA): a prospective, randomised, multicentre study. Lancet. 2020;395(10231):1208-1216. doi:10.1016/S0140-6736(20)30314-7

Erdem S, Simsek DH, Degirmenci E, et al. How accurate is 68Gallium-prostate specific membrane antigen positron emission tomography/computed tomography (68Ga-PSMA PET/CT) on primary lymph node staging before radical prostatectomy in intermediate and high risk prostate cancer? A study of patient- and lymph node- based analyses. Urol Oncol Semin Orig Invest. 2022;40(1):6.e1-6.e9. doi:10.1016/j.urolonc.2021.07.006

Freedland SJ, Hotaling JM, Fitzsimons NJ, et al. PSA in the new millennium: a powerful predictor of prostate cancer prognosis and radical prostatectomy outcomes-results from the SEARCH database. Eur Urol. 2008;53(4):758-766. doi:10.1016/j.eururo.2007.08.047

Inman BA, Davies JD, Rangel LJ, et al. Long-term outcomes of radical prostatectomy with multimodal adjuvant therapy in men with a preoperative serum prostate-specific antigen level ≥50 ng/ml. Cancer. 2008;113(7):1544-1551. doi:10.1002/cncr.23767

Gontero P, Spahn M, Tombal B, et al. Is there a prostate-specific antigen upper limit for radical prostatectomy? BJU Int. 2011;108(7):1093-1100. doi:10.1111/j.1464-410X.2011.10076.x

Tilki D, Mandel P, Karakiewicz PI, et al. The impact of very high initial PSA on oncological outcomes after radical prostatectomy for clinically localized prostate cancer. Urol Oncol Semin Original Invest. 2020;38(5):379-385. doi:10.1016/j.urolonc.2019.12.027

Izumi K, Lin WJ, Miyamoto H, et al. Outcomes and predictive factors of prostate cancer patients with extremely high prostate-specific antigen level. J Cancer Res Clin Oncol. 2014;140(8):1413-1419. doi:10.1007/s00432-014-1681-8

Hochreiter WW. The issue of prostate cancer evaluation in men with elevated prostate-specific antigen and chronic prostatitis. Andrologia. 2008;40(2):130-133. doi:10.1111/j.1439-0272.2007.00820.x