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. 2023 Sep 5;6(9):e2332900.
doi: 10.1001/jamanetworkopen.2023.32900.

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Ugo Giovanni Falagario  1   2 , Ahmad Abbadi  3 , Sebastiaan Remmers  4 , Lars Björnebo  3 , Darko Bogdanovic  3 , Alberto Martini  5 , Alexander Valdman  6 , Giuseppe Carrieri  2 , Mani Menon  7 , Olof Akre  1 , Martin Eklund  3 , Tobias Nordström  3   8 , Henrik Grönberg  3 , Anna Lantz  1   3 , Peter Wiklund  1   7
Affiliations

Biochemical Recurrence and Risk of Mortality Following Radiotherapy or Radical Prostatectomy

Ugo Giovanni Falagario et al. JAMA Netw Open. .

Abstract

Importance: Stratifying patients with biochemical recurrence (BCR) after primary treatment for prostate cancer based on the risk of prostate cancer-specific mortality (PCSM) is essential for determining the need for further testing and treatments.

Objective: To evaluate the association of BCR after radical prostatectomy or radiotherapy and its current risk stratification with PCSM.

Design, setting, and participants: This population-based cohort study included a total of 16 311 male patients with 10 364 (64%) undergoing radical prostatectomy and 5947 (36%) undergoing radiotherapy with curative intent (cT1-3, cM0) and PSA follow-up in Stockholm, Sweden, between 2003 and 2019. Follow-up for all patients was until death, emigration, or end of the study (ie, December 31, 2018). Data were analyzed between September 2022 and March 2023.

Main outcomes and measures: Primary outcomes of the study were the cumulative incidence of BCR and PCSM. Patients with BCR were stratified in low- and high-risk according to European Association of Urology (EAU) criteria.

Exposures: Radical prostatectomy or radiotherapy.

Results: A total of 16 311 patients were included. Median (IQR) age was 64 (59-68) years in the radical prostatectomy cohort (10 364 patients) and 69 (64-73) years in the radiotherapy cohort (5947 patients). Median (IQR) follow-up for survivors was 88 (55-138) months and 89 (53-134) months, respectively. Following radical prostatectomy, the 15-year cumulative incidences of BCR were 16% (95% CI, 15%-18%) for the 4024 patients in the low D'Amico risk group, 30% (95% CI, 27%-32%) for the 5239 patients in the intermediate D'Amico risk group, and 46% (95% CI, 42%-51%) for 1101 patients in the high D'Amico risk group. Following radiotherapy, the 15-year cumulative incidences of BCR were 18% (95% CI, 15%-21%) for the 1230 patients in the low-risk group, 24% (95% CI, 21%-26%) for the 2355 patients in the intermediate-risk group, and 36% (95% CI, 33%-39%) for the 2362 patients in the high-risk group. The 10-year cumulative incidences of PCSM after radical prostatectomy were 4% (95% CI, 2%-6%) for the 1101 patients who developed low-risk EAU-BCR and 9% (95% CI, 5%-13%) for 649 patients who developed high-risk EAU-BCR. After radiotherapy, the 10-year PCSM cumulative incidences were 24% (95% CI, 19%-29%) for the 591 patients in the low-risk EAU-BCR category and 46% (95% CI, 40%-51%) for the 600 patients in the high-risk EAU-BCR category.

Conclusions and relevance: These findings suggest the validity of EAU-BCR stratification system. However, while the risk of dying from prostate cancer in low-risk EAU-BCR after radical prostatectomy was very low, patients who developed low-risk EAU-BCR after radiotherapy had a nonnegligible risk of prostate cancer mortality. Improving risk stratification of patients with BCR is pivotal to guide salvage treatment decisions, reduce overtreatment, and limit the number of staging tests in the event of PSA elevations after primary treatment.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Martini reported having ownership of equities of Oltre Medical Consulting. Dr Eklund reported receiving grants from the Swedish Research Council, Swedish Cancer Society, and the Swedish Prostate Cancer Society during the conduct of the study; being a stockholder of A3P Biomedical AB and Clinsight AB outside the submitted work; having patents pending for refined prostate cancer risk assessment for low-risk cases, for indicating a presence of aggressive prostate cancer, and for estimating the need for prostate cancer therapy. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Cumulative Incidence Function Curves for Biochemical Recurrence (BCR) According to D’Amico Risk Groups at Diagnosis
Figure 2.
Figure 2.. Cumulative Incidence Function Curves Demonstrating Prostate Cancer–Specific Mortality (PCSM) After Biochemical Recurrence (BCR) According to EAU BCR Risk Classification
Adjusted for salvage treatment. Harrell C was 0.66 (95% CI, 0.57-0.75) in the radical prostatectomy group and 0.69 (95% CI, 0.66-0.72) in the radiotherapy groups.
See this image and copyright information in PMC

References

    1. Stamey TA, Yang N, Hay AR, McNeal JE, Freiha FS, Redwine E. Prostate-specific antigen as a serum marker for adenocarcinoma of the prostate. N Engl J Med. 1987;317(15):909-916. doi:10.1056/NEJM198710083171501 - DOI - PubMed
    1. Mottet N, van den Bergh RCN, Briers E, et al. . EAU - ESTRO - ESUR - SIOG Guidelines on Prostate Cancer 2022. European Association of Urology Guidelines. 2022 Edition. European Association of Urology Guidelines Office; 2022.
    1. Van den Broeck T, van den Bergh RCN, Arfi N, et al. . Prognostic value of biochemical recurrence following treatment with curative intent for prostate cancer: a systematic review. Eur Urol. 2019;75(6):967-987. doi:10.1016/j.eururo.2018.10.011 - DOI - PubMed
    1. Tilki D, Preisser F, Graefen M, Huland H, Pompe RS. External validation of the european association of urology biochemical recurrence risk groups to predict metastasis and mortality after radical prostatectomy in a European cohort. Eur Urol. 2019;75(6):896-900. doi:10.1016/j.eururo.2019.03.016 - DOI - PubMed
    1. Pak S, Lee DE, You D, et al. . Validation of the European association of urology biochemical recurrence risk groups after radical prostatectomy in an Asian cohort and suggestions for refinement. Urol Oncol. 2021;39(5):298e1-298e6. doi:10.1016/j.urolonc.2020.12.023 - DOI - PubMed

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