Prognostic impact of PSA nadir (n) ≥0.1 ng/mL within 6 months (m) after completion of radiotherapy (RT) for localized prostate cancer (PCa): An individual patient-data (IPD) analysis of randomized trials from the ICECAP collaborative.

Authors

Praful Ravi

Praful Ravi

Dana-Farber Cancer Institute, Boston, MA

Praful Ravi , Lucia Kwak , John Armstrong , Veronique Beckendorf , Joseph Chin , Anthony Victor D'Amico , David P. Dearnaley , James William Denham , Savino Mauro Di Stasi , Silke Gillessen , Himanshu Lukka , Nicolas Mottet Auselo , Pascal Pommier , Wendy Seiferheld , Matthew R. Sydes , Bertrand F. Tombal , Almudena Zapatero , Meredith M. Regan , Wanling Xie , Christopher Sweeney

Organizations

Dana-Farber Cancer Institute, Boston, MA, Cancer Trials Ireland, St. Luke’s Hospital, Radiation Oncology Department, Dublin, Ireland, Institut de cancérologie de Lorraine, Nancy, France, Division of Urology, London Health Sciences Centre, London, ON, Canada, Brigham and Women's Hospital, Boston, MA, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom, Calvary Mater Newcastle, Georgetown, NSW, Australia, Tor Vergata University of Rome, Rome, Italy, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland, McMaster University and Juravinski Cancer Centre, Hamilton, ON, Canada, MUTUALITE FRANCAISE LOIRE, ST Etienne, ICO, Angers, France, NRG Oncology, Philadelphia, PA, Medical Research Council at UCL, London, United Kingdom, Cliniques Universitaires Saint-Luc, Brussels, Belgium, Hospital Universitario de La Princesa, Madrid, Spain, Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, South Australian Immunogenomics Cancer Institute, University of Adelaide, Adelaide, Australia

Research Funding

No funding received
None.

Background: RT + androgen deprivation therapy (ADT) is a standard of care in treatment of intermediate- and high-risk localized PCa. Identification of early surrogate measures for long-term outcome measures such as PCa-specific survival (PCSS), metastasis-free survival (MFS) and overall survival (OS) could expedite development of new systemic therapies added to RT/ADT while potentially identifying patients (pts) for therapy (de)escalation. Methods: IPD from the RT+/-ADT trials in the ICECAP repository with evaluable PSA follow-up were eligible for inclusion. Pts were grouped based on their trial-allocated treatment: RT alone, RT+stADT (short-term ADT: 3-6m), RT+ltADT (long-term ADT: 18-36m). PSAn was defined as the lowest PSA recorded within 6m after RT completion. A 12m landmark analysis for PCSS, MFS and OS was performed to account for guarantee-time bias. Multivariable Cox proportional hazards regression was used to estimate associations of PSAn < or ≥0.1ng/mL with MFS and OS, and a multivariable Fine and Gray distribution used for PCSS to account for competing risk of non-PCa deaths. Models were adjusted for age, ECOG performance status, clinical T stage, Gleason score and PSA at randomization. Results: 10,415 pts from 16 RCTs were included: 2629 (25%) allocated to RT, 6033 (58%) to RT+stADT, and 1753 (17%) to RT+ltADT. Median follow-up was 10.1years (yrs). 2339 (98%), 4756 (84%) and 1258 (77%) of patients allocated to RT, RT+stADT and RT+ltADT respectively achieved a PSAn ≥0.1ng/mL within 6m after RT completion. After adjustment, PSAn ≥0.1ng/mL was associated with poorer PCSS, MFS and OS in pts allocated to RT+stADT (PCSS hazard ratio [HR] = 1.97 [95% CI 1.52-2.92], MFS HR = 1.27 [1.12-1.44], OS HR = 1.26 [1.11-1.44]) and RT+ltADT (PCSS HR = 1.97 [1.11-3.49], MFS HR = 1.58 [1.27-1.96], OS HR = 1.59 [1.27-1.99]). A weaker association was noted in pts allocated to RT (PCSS HR = 1.82 [0.51-6.49], MFS HR = 2.23 [1.20-4.14], OS HR = 1.72 [0.97-3.05]). Table shows 5-yr MFS, 10-yr PCSS and 10-yr OS based on PSAn within 6m after RT completion. Conclusions: PSAn ≥0.1ng/mL within 6 mths after RT completion was strongly prognostic for PCSS, MFS and OS in pts receiving RT+ADT for localized PCa in this IPD analysis of > 10,000 patients. This could be used as an early signal-seeking endpoint in trials evaluating novel systemic therapies with RT + ADT and to help identify pts for therapy (de)escalation trials.

RT only (n = 2376)RT + stADT (n = 5658)RT + ltADT (n = 1626)
5-year MFS, %
PSAn < 0.1ng/mL
PSAn ≥0.1ng/mL

91 (74-97)
79 (77-81)

83 (80-85)
76 (74-77)

87 (83-91)
74 (71-76)
10-year PCSS, %
PSAn < 0.1ng/mL
PSAn ≥0.1ng/mL

92 (72-98)
84 (81-86)

91 (86-94)
83 (82-85)

88 (79-94)
83 (80-86)
10-year OS, %
PSAn < 0.1ng/mL
PSAn ≥0.1ng/mL

52 (31-69)
58 (55-61)

62 (57-67)
56 (54-57)

63 (54-71)
50 (47-54)

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Abstract Details

Meeting

2023 ASCO Annual Meeting

Session Type

Oral Abstract Session

Session Title

Genitourinary Cancer—Prostate, Testicular, and Penile

Track

Genitourinary Cancer—Prostate, Testicular, and Penile

Sub Track

Prostate Cancer–Local-Regional Disease

Citation

J Clin Oncol 41, 2023 (suppl 16; abstr 5002)

DOI

10.1200/JCO.2023.41.16_suppl.5002

Abstract #

5002

Abstract Disclosures

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