Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer

Rebecca G Philipson¹, Tahmineh Romero², Jessica K Wong³, Bradley J Stish⁴, Robert T Dess⁵, Daniel E Spratt⁵, Avinash Pilar⁶, Chandana Reddy⁷, Trude B Wedde⁸, Wolfgang A Lilleby⁸, Ryan Fiano⁹, Gregory S Merrick⁹, Richard G Stock¹⁰, D Jeffrey Demanes¹¹, Brian J Moran¹², Michelle Braccioforte¹², Phuoc T Tran¹³, Santiago Martin¹⁴, Rafael Martinez-Monge¹⁴, Daniel J Krauss¹⁵, Eyad I Abu-Isa⁵, Luca Valle¹, Natalie Chong¹, Thomas M Pisansky⁴, C Richard Choo⁴, Daniel Y Song¹³, Stephen Greco¹³, Curtiland Deville¹³, Todd McNutt¹³, Theodore L DeWeese¹³, Ashley E Ross¹⁶, Jay P Ciezki⁷, Derya Tilki¹⁷, R Jeffrey Karnes¹⁸, Eric A Klein¹⁹, Jeffrey J Tosoian²⁰, Paul C Boutros²¹, Nicholas G Nickols²², Prashant Bhat²³, David Shabsovich²³, Jesus E Juarez²³, Patrick A Kupelian¹, Matthew B Rettig²⁴, Alejandro Berlin²⁵, Jonathan D Tward²⁶, Brian J Davis⁴, Robert E Reiter²¹, Michael L Steinberg¹, David Elashoff², Eric M Horwitz³, Rahul D Tendulkar⁷, Amar U Kishan²⁷

Affiliations

¹ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
² UCLA Division of General Internal Medicine and Health Services Research, Los Angeles, CA, USA.
³ Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁴ Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
⁵ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁶ Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada.
⁷ Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁸ Oslo University Hospital, Oslo, Norway.
⁹ Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, WV, USA.
¹⁰ Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ California Endocurietherapy Cancer Center, Oakland, CA, USA.
¹² Chicago Prostate Cancer Center, Westmont, IL, USA.
¹³ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴ Department of Radiation Oncology, Clínica Universidad de Navarra and Program in Solid Tumors, CIMA- University of Navarra, Pamplona, Spain.
¹⁵ Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA.
¹⁶ Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ Department of Urology and Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ Department of Urology, Mayo Clinic, Rochester, MN, USA.
¹⁹ Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
²⁰ Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²¹ Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.
²² Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, West Los Angeles Veterans Health Administration, Los Angeles, CA, USA.
²³ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
²⁴ Department of Medical Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Medical Oncology, West Los Angeles Veterans Health Administration, Los Angeles, CA, USA.
²⁵ Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
²⁶ Department of Radiotherapy Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA.
²⁷ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.

PMID: 33985797
PMCID: PMC10262978
DOI: 10.1016/j.eururo.2021.04.035

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer

Rebecca G Philipson et al. Eur Urol. 2021 Aug.

. 2021 Aug;80(2):142-146.

doi: 10.1016/j.eururo.2021.04.035. Epub 2021 May 10.

Authors

Affiliations

¹ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
² UCLA Division of General Internal Medicine and Health Services Research, Los Angeles, CA, USA.
³ Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.
⁴ Department of Radiation Oncology, Mayo Clinic, Rochester, MN, USA.
⁵ Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, USA.
⁶ Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada.
⁷ Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA.
⁸ Oslo University Hospital, Oslo, Norway.
⁹ Schiffler Cancer Center, Wheeling Hospital, Wheeling Jesuit University, Wheeling, WV, USA.
¹⁰ Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹¹ California Endocurietherapy Cancer Center, Oakland, CA, USA.
¹² Chicago Prostate Cancer Center, Westmont, IL, USA.
¹³ Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
¹⁴ Department of Radiation Oncology, Clínica Universidad de Navarra and Program in Solid Tumors, CIMA- University of Navarra, Pamplona, Spain.
¹⁵ Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA.
¹⁶ Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
¹⁷ Department of Urology and Martini-Klinik Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
¹⁸ Department of Urology, Mayo Clinic, Rochester, MN, USA.
¹⁹ Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA.
²⁰ Department of Urology, The James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
²¹ Department of Urology, University of California Los Angeles, Los Angeles, CA, USA.
²² Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Radiation Oncology, West Los Angeles Veterans Health Administration, Los Angeles, CA, USA.
²³ David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
²⁴ Department of Medical Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Medical Oncology, West Los Angeles Veterans Health Administration, Los Angeles, CA, USA.
²⁵ Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada.
²⁶ Department of Radiotherapy Oncology, Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT, USA.
²⁷ Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA; Department of Urology, University of California Los Angeles, Los Angeles, CA, USA. Electronic address: aukishan@mednet.ucla.edu.

PMID: 33985797
PMCID: PMC10262978
DOI: 10.1016/j.eururo.2021.04.035

Abstract

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p < 0.001) and PCSM (p < 0.001). These data suggest that radiorecurrent HRPCa has an aggressive natural history and that DM is clinically evident early after BCR. These findings underscore the importance of further investigations into upfront risk assessment and prompt systemic evaluation upon recurrence in HRPCa. PATIENT SUMMARY: High-risk prostate cancer that recurs after radiation therapy is an aggressive disease entity and spreads to other parts of the body (metastases). Some 60% of metastases occur within 1 yr. Approximately 30% of these patients die from their prostate cancer.

Keywords: Biochemical recurrence; Brachytherapy boost; EBRT; External beam radiation therapy; High-risk prostate cancer; Prostate cancer; Radiorecurrence; Recurrent prostate cancer.

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Conflict of interest statement

Financial disclosures: Amar U. Kishan certifies that all conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript (eg, employment/affiliation, grants or funding, consultancies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following: Nicholas G. Nickols has received grants from Veterans Affairs, Prostate Cancer Foundation, STOP Cancer Foundation, Janssen, Bayer, Progenics, and Varian; and personal fees from Gene Sciences, Inc. Matthew B. Rettig has received research grants from Novartis, Johnson & Johnson, Merck, Astellas, and Medivation; is a member of speaker bureaus for Johnson & Johnson and Bayer; and is a consultant for Constellation, Ambrx, and Amgen. Daniel E. Spratt is an advisory board member for Blue Earth Diagnostics, Janssen, and AstraZeneca. Jonathan D. Tward has received research funding from Bayer and Myriad; acts in a consulting role for Bayer, Blue Earth, Merck, and Astellas; and participates in a speaker bureau for Blue Earth. Jeffrey J. Tosoian holds a leadership role with equity interest in LynxDx, Inc. Paul C. Boutros is a member of the scientific advisory boards of BioSymetrics Inc. and of Intersect Diagnostics Inc. Amar U. Kishan has acted in an advisory role for Janssen and a consulting role for mPROS; has received grants from the Prostate Cancer Foundation; and has received honoraria from Varian and ViewRay. The remaining authors have nothing to disclose.

Figures

**Fig. 1 –**
Kaplan-Meier curves for (A,B) distant metastasis–free survival and (C,D) prostate cancer–specific survival following biochemical recurrence (BCR) in men with high-risk prostate cancer treated initially with external beam radiotherapy (EBRT) or external beam radiotherapy plus brachytherapy boost (EBRT + BT). (A) Distant metastasis–free survival following BCR after EBRT. (B) Distant metastasis–free survival following BCR after EBRT + BT. (C) Prostate cancer–specific survival following BCR after EBRT. (D) Prostate cancer–specific survival following BCR after EBRT + BT.

See this image and copyright information in PMC

Comment in

High-risk Prostate Cancer Treated with Radiation Therapy: Opportunities to Reduce Cancer Mortality after Biochemical Failure.
Liauw SL. Liauw SL. Eur Urol. 2021 Aug;80(2):147-148. doi: 10.1016/j.eururo.2021.05.023. Epub 2021 May 28. Eur Urol. 2021. PMID: 34053781 No abstract available.

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Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer

Affiliations

Patterns of Clinical Progression in Radiorecurrent High-risk Prostate Cancer

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical