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Association of dynamic change in patient-reported pain with survival in metastatic castrate sensitive prostate cancer—exploratory analysis of LATITUDE study

Prostate Cancer and Prostatic Diseases volume 26, pages 96–104 (2023)Cite this article

Subjects

Abstract

Background

Pain is an important dimension of quality-of-life in patients with metastatic castrate-sensitive prostate cancer (mCSPC). However, it is unclear if dynamic change in pain over time can predict for overall survival (OS) or progression-free survival (PFS) in these patients.

Methods

This is an exploratory analysis of LATITUDE, a phase III randomized study, in which men with de novo mCSPC were randomized to receive either ADT plus abiraterone versus ADT alone. Information was collected on patient-reported worst pain score (WPS) and pain-interference score (PIS) from the Brief Pain Inventory-Short Form. A Bayesian joint modelling approach was used determine the association of dynamic change in WPS and PIS with OS and PFS.

Results

Overall, 1125 patients with at least 3 measurements on pain scores were eligible. On Cox multivariable regression, increase in baseline WPS was associated with inferior OS (hazard ratio [HR] 1.049 [95% confidence intervals [CI] 1.015–1.085]; time dependent area under curve [tAUC] 0.64) and PFS (HR 1.045 [1.011–1.080]; tAUC: 0.64). Increase in baseline PIS was associated with inferior OS (HR 1.062 [1.020–1.105]; tAUC: 0.63) but not with PFS (HR 1.038 [0.996–1.08]). On independent joint models, an increase in the current value of WPS by 1-unit was associated with inferior OS (HR 1.316 [1.258–1.376]; tAUC 0.74) and PFS (HR 1.319 [1.260–1.382]; tAUC 0.70). Similar association was seen for increase in the current value of PIS with OS (HR 1.319 [1.261–1.381]; tAUC 0.73) and PFS (HR 1.282 [1.224–1.344]; tAUC 0.73).

Conclusions

The above findings highlight the potential dynamic interplay between patient-reported pain with OS and PFS in mCSPC. Compared to baseline pain, such dynamic assessment of pain was found to have superior predictive ability and thus has the potential to tailor subsequent treatment based on response to initial therapy beyond its role as a very important dimension of quality-of-life.

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Fig. 1: Shows the progression-free survival (PFS) and overall survival (OS) by treatment regimen.

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Funding

None. The original LATITUDE study was funded by Janssen Oncology. However, the employees of the funder had no role in study design, data collection, data analysis, data interpretation, and writing of this report. The corresponding authors had full access to all data in the study and final responsibility for the decision to submit for publication.

Author information

Author notes

  1. These authors contributed equally: Scott C. Morgan, Christopher J. D. Wallis, Yilun Sun, Daniel E. Spratt, Fred Saad.

Authors and Affiliations

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

    Soumyajit Roy

  2. Radiation Medicine Program, The Ottawa Hospital Cancer Centre, University of Ottawa, Ottawa, ON, Canada

    Scott C. Morgan, Scott Grimes & Shawn Malone

  3. Division of Urology, University of Toronto; Mount Sinai Hospital, Toronto, ON, Canada

    Christopher J. D. Wallis

  4. Department of Population and Quantitative Health Sciences, School of Medicine, Case Western Reserve University, Cleveland, OH, USA

    Yilun Sun

  5. University Hospital Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA

    Daniel E. Spratt

  6. University of Ottawa, Ottawa, ON, Canada

    Julia Malone

  7. Institute of Computational Biology, Bengaluru, India

    Dibya Mukherjee

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

    Amar U. Kishan

  9. Department of surgery, Université de Montréal, Montreal, QC, Canada

    Fred Saad

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Contributions

Conception and design: SR and SM. Administrative support: SM, CW, SR DM, JM, DS. Provision of study material or patients: SM, SCM, SR, CW, FS, AUK. Collection and assembly of data: SM, SR, YS, SCM, FS, DM, and SG. Data analysis and interpretation: YS, SR. Manuscript writing: all authors. Final approval of manuscript: all authors. Accountable for all aspects of the work: all authors.

Corresponding authors

Correspondence to Soumyajit Roy or Shawn Malone.

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Data sharing and declaration

This study, carried out under YODA Project # 2021-4566, used data obtained from the Yale University Open Data Access Project, which has an agreement with JANSSEN RESEARCH & DEVELOPMENT, L.L.C. The interpretation and reporting of research using this data are solely the responsibility of the authors and does not necessarily represent the official views of the Yale University Open Data Access Project or JANSSEN RESEARCH & DEVELOPMENT, L.L.C.

Competing interests

Outside of this work, Dr. Malone has received honoraria from Astellas, Bayer, Janssen, and Sanofi; and travel and accommodations support from TerSera and Sanofi. Outside of this work, Dr. Morgan reports personal fees from Astellas, Bayer, Janssen, and TerSera. Dr. Roy reports research grant from Abbvie-Canadian Association of Radiation Oncology. Dr. Wallis has received honoraria from Knight Therapeutics AND Haymarket Media and reports other from Janssen Oncology, other from SESEN Bio, outside the submitted work. Honoraria. Dr. Saad reports grants, personal fees, and non-financial support from Janssen, during the conduct of the study; grants, personal fees, and non-financial support from Astellas, grants, personal fees, and non-financial support from Bayer, outside the submitted work. Dr. Spratt reports personal fees from Blue Earth, personal fees from Janssen, personal fees from AstraZeneca, Gammatile, Varian, and Boston Scientific, outside the submitted work. Dr, Kishan reports personal fees and research support from ViewRay, Inc., and personal fees from Varian Medical Systems, Inc., and Intelligent Automation, Inc., outside the submitted work. The other coauthors have no competing financial interests.

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Roy, S., Morgan, S.C., Wallis, C.J.D. et al. Association of dynamic change in patient-reported pain with survival in metastatic castrate sensitive prostate cancer—exploratory analysis of LATITUDE study. Prostate Cancer Prostatic Dis 26, 96–104 (2023). https://doi.org/10.1038/s41391-022-00529-2

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