Refining the definition of biochemical failure in the era of stereotactic body radiation therapy for prostate cancer: The Phoenix definition and beyond.

Biochemical failure PSA PSA bounce Phoenix definition Prostate cancer Stereotactic body radiation therapy (SBRT)

Journal

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ISSN: 1879-0887
Titre abrégé: Radiother Oncol
Pays: Ireland
ID NLM: 8407192

Informations de publication

Date de publication:
01 2022
Historique:
received: 20 09 2021
revised: 01 11 2021
accepted: 02 11 2021
pubmed: 15 11 2021
medline: 20 4 2022
entrez: 14 11 2021
Statut: ppublish

Résumé

The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs. PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA Median follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%. The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

Sections du résumé

BACKGROUND AND PURPOSE
The Phoenix definition for biochemical failure (BCF) after radiotherapy uses nadir PSA (nPSA) + 2 ng/mL to classify a BCF and was derived from conventionally fractionated radiotherapy, which produces significantly higher nPSAs than stereotactic body radiotherapy (SBRT). We investigated whether an alternative nPSA-based threshold could be used to define post-SBRT BCFs.
MATERIALS AND METHODS
PSA kinetics data on 2038 patients from 9 institutions were retrospectively analyzed for low- and intermediate-risk PCa patients treated with SBRT without ADT. We evaluated the performance of various nPSA-based definitions. We also investigated the relationship of relative PSA decline (rPSA, PSA
RESULTS
Median follow-up was 71.9 months. BCF occurred in 6.9% of patients. Median nPSA was 0.16 ng/mL. False positivity of nPSA + 2 was 30.2%, compared to 40.9%, 57.8%, and 71.0% for nPSA + 1.5, nPSA + 1.0, and nPSA + 0.5, respectively. Among patients with BCF, the median lead time gained from an earlier nPSA + threshold definition over the Phoenix definition was minimal. Patients with BCF had significantly lower rates of early PSA decline (mean rPSA 1.19 vs. 0.39, p < 0.0001) and were significantly more likely to reach nPSA + 2 ≥ 18 months (83.3% vs. 21.1%, p < 0.0001). The proposed criterion (rPSA ≥ 2.6 or nPSA + 2 ≥ 18 months) had a sensitivity and specificity of 92.4% and 81.5%, respectively, for predicting BCF in patients meeting the Phoenix definition and decreased its false positivity to 6.4%.
CONCLUSION
The Phoenix definition remains an excellent definition for BCF post-SBRT. Its high false positivity can be mitigated by applying additional criteria (rPSA ≥ 2.6 or time to nPSA + 2 ≥ 18 months).

Identifiants

pubmed: 34774650
pii: S0167-8140(21)08797-1
doi: 10.1016/j.radonc.2021.11.005
pii:
doi:

Substances chimiques

Prostate-Specific Antigen EC 3.4.21.77

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1-7

Subventions

Organisme : NCI NIH HHS
ID : P50 CA092131
Pays : United States

Informations de copyright

Copyright © 2021 Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest A.U.K. reports funding support from grant P50CA09213 from the Prostate Cancer National Institutes of Health Specialized Programs of Research Excellence, as well as grant RSD1836 from the Radiological Society of North America, the STOP Cancer organization, the Jonsson Comprehensive Cancer Center, and the Prostate Cancer Foundation. N.N. reports research support from Janssen and Lantheus, and consulting for Oncolinea. All other authors have no conflict of interest to declare.

Auteurs

Ting Martin Ma (TM)

Department of Radiation Oncology, University of California Los Angeles, USA.

Soumyajit Roy (S)

Department of Radiation Oncology, Rush University Medical Center, Chicago, USA.

Xue Wu (X)

Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, USA.

Constantine Mantz (C)

21st Century Oncology, Fort Myers, USA.

Donald Fuller (D)

Division of Genesis Healthcare Partners Inc, CyberKnife Centers of San Diego Inc, USA.

Leszek Miszczyk (L)

Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.

Alexandra Napieralska (A)

Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.

Agnieska Namysł-Kaletka (A)

Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.

Hilary P Bagshaw (HP)

Department of Radiation Oncology, Stanford University School of Medicine, USA.

Mark K Buyyounouski (MK)

Department of Radiation Oncology, Stanford University School of Medicine, USA.

Rachel Glicksman (R)

Department of Radiation Oncology, University of Toronto, Canada.

D Andrew Loblaw (DA)

Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada.

Alan Katz (A)

St. Francis Hospital, Roslyn, USA.

Shrinivasa K Upadhyaya (SK)

Department of Biological and Agricultural Engineering, University of California, Davis, USA.

Nicholas Nickols (N)

Department of Radiation Oncology, University of California Los Angeles, USA.

Michael L Steinberg (ML)

Department of Radiation Oncology, University of California Los Angeles, USA.

Rebecca Philipson (R)

Department of Radiation Oncology, Torrance Memorial Hospital, USA.

Nima Aghdam (N)

Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, USA.

Simeng Suy (S)

Department of Radiation Medicine, Georgetown University Hospital, Washington D.C., USA.

Abigail Pepin (A)

University of Pennsylvania Health System, Philadelphia, USA.

Sean P Collins (SP)

Department of Radiation Medicine, Georgetown University Hospital, Washington D.C., USA.

Paul Boutros (P)

University of Pennsylvania Health System, Philadelphia, USA.

Matthew B Rettig (MB)

Department Urology, University of California Los Angeles, USA.

Jeremie Calais (J)

Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, USA.

Ming Wang (M)

Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, USA.

Nicholas Zaorsky (N)

Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, USA.

Amar U Kishan (AU)

Department of Radiation Oncology, University of California Los Angeles, USA. Electronic address: Aukishan@mednet.ucla.edu.

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