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

Ting Martin Ma; Soumyajit Roy; Xue Wu; Constantine Mantz; Donald Fuller; Leszek Miszczyk; Alexandra Napieralska; Agnieska Namysł-Kaletka; Hilary P Bagshaw; Mark K Buyyounouski; Rachel Glicksman; D Andrew Loblaw; Alan Katz; Shrinivasa K Upadhyaya; Nicholas Nickols; Michael L Steinberg; Rebecca Philipson; Nima Aghdam; Simeng Suy; Abigail Pepin; Sean P Collins; Paul Boutros; Matthew B Rettig; Jeremie Calais; Ming Wang; Nicholas Zaorsky; Amar U Kishan

doi:10.1016/j.radonc.2021.11.005

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

Radiother Oncol. 2022 Jan:166:1-7. doi: 10.1016/j.radonc.2021.11.005. Epub 2021 Nov 11.

Authors

Ting Martin Ma¹, Soumyajit Roy², Xue Wu³, Constantine Mantz⁴, Donald Fuller⁵, Leszek Miszczyk⁶, Alexandra Napieralska⁶, Agnieska Namysł-Kaletka⁶, Hilary P Bagshaw⁷, Mark K Buyyounouski⁷, Rachel Glicksman⁸, D Andrew Loblaw⁹, Alan Katz¹⁰, Shrinivasa K Upadhyaya¹¹, Nicholas Nickols¹, Michael L Steinberg¹, Rebecca Philipson¹², Nima Aghdam¹³, Simeng Suy¹⁴, Abigail Pepin¹⁵, Sean P Collins¹⁴, Paul Boutros¹⁵, Matthew B Rettig¹⁶, Jeremie Calais¹⁷, Ming Wang³, Nicholas Zaorsky¹⁸, Amar U Kishan¹⁹

Affiliations

¹ Department of Radiation Oncology, University of California Los Angeles, USA.
² Department of Radiation Oncology, Rush University Medical Center, Chicago, USA.
³ Division of Biostatistics and Bioinformatics, Department of Public Health Sciences, Penn State College of Medicine, Hershey, USA.
⁴ 21st Century Oncology, Fort Myers, USA.
⁵ Division of Genesis Healthcare Partners Inc, CyberKnife Centers of San Diego Inc, USA.
⁶ Department of Radiotherapy, Maria Sklodowska-Curie National Research Institute of Oncology Gliwice Branch, Poland.
⁷ Department of Radiation Oncology, Stanford University School of Medicine, USA.
⁸ Department of Radiation Oncology, University of Toronto, Canada.
⁹ Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Canada.
¹⁰ St. Francis Hospital, Roslyn, USA.
¹¹ Department of Biological and Agricultural Engineering, University of California, Davis, USA.
¹² Department of Radiation Oncology, Torrance Memorial Hospital, USA.
¹³ Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Boston, USA.
¹⁴ Department of Radiation Medicine, Georgetown University Hospital, Washington D.C., USA.
¹⁵ University of Pennsylvania Health System, Philadelphia, USA.
¹⁶ Department Urology, University of California Los Angeles, USA.
¹⁷ Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, University of California Los Angeles, USA.
¹⁸ Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, USA.
¹⁹ Department of Radiation Oncology, University of California Los Angeles, USA. Electronic address: Aukishan@mednet.ucla.edu.

PMID: 34774650
DOI: 10.1016/j.radonc.2021.11.005

Abstract

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_18month/PSA_6month) and timing of reaching nPSA + 2 with BCF.

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).

Keywords: Biochemical failure; PSA; PSA bounce; Phoenix definition; Prostate cancer; Stereotactic body radiation therapy (SBRT).

Publication types

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

MeSH terms

Brachytherapy*
Humans
Male
Prostate-Specific Antigen
Prostatic Neoplasms* / radiotherapy
Prostatic Neoplasms* / surgery
Radiosurgery*
Retrospective Studies

Substances

Prostate-Specific Antigen

Grants and funding

P50 CA092131/CA/NCI NIH HHS/United States