A pilot study of a multimodal treatment paradigm to accelerate drug evaluations in early-stage metastatic prostate cancer Journal Article

Authors: O'Shaughnessy, M. J.; McBride, S. M.; Vargas, H. A.; Touijer, K. A.; Morris, M. J.; Danila, D. C.; Laudone, V. P.; Bochner, B. H.; Sheinfeld, J.; Dayan, E. S.; Bellomo, L. P.; Sjoberg, D. D.; Heller, G.; Zelefsky, M. J.; Eastham, J. A.; Scardino, P. T.; Scher, H. I.
Article Title: A pilot study of a multimodal treatment paradigm to accelerate drug evaluations in early-stage metastatic prostate cancer
Abstract: Objective To evaluate a multimodal strategy aimed at treating all sites of disease that provides a rapid readout of success or failure in men presenting with non-castrate metastatic prostate cancers that are incurable with single modality therapy. Materials and Methods Twenty selected men with oligometastatic M1a (extrapelvic nodal disease) or M1b (bone disease) at diagnosis were treated using a multimodal approach that included androgen deprivation, radical prostatectomy plus pelvic lymphadenectomy (retroperitoneal lymphadenectomy in the presence of clinically positive retroperitoneal nodes), and stereotactic body radiotherapy to osseous disease or the primary site. Outcomes of each treatment were assessed sequentially. Androgen deprivation was discontinued in responding patients. The primary end point was an undetectable prostate-specific antigen (PSA) after testosterone recovery. The goal was to eliminate all detectable disease. Results Each treatment modality contributed to the outcome: 95% of the cohort achieved an undetectable PSA with multimodal treatment, including 25% of patients after androgen deprivation alone and an additional 50% and 20% after surgery and radiotherapy, respectively. Overall, 20% of patients (95% confidence interval: 3%-38%) achieved the primary end point, which persisted for 5, 6, 27+, and 46+ months. All patients meeting the primary end point had been classified with M1b disease at presentation. Conclusion A sequentially applied multimodal treatment strategy can eliminate detectable disease in selected patients with metastatic spread at diagnosis. The end point of undetectable PSA after testosterone recovery should be considered when evaluating new approaches to rapidly set priorities for large-scale testing in early metastatic disease states and to shift the paradigm from palliation to cure. © 2016 Elsevier Inc.
Journal Title: Urology
Volume: 102
ISSN: 0090-4295
Publisher: Elsevier Science, Inc.  
Date Published: 2017-04-01
Start Page: 164
End Page: 171
Language: English
DOI: 10.1016/j.urology.2016.10.044
PROVIDER: scopus
PMCID: PMC5468169
PUBMED: 27888148
Notes: Article -- Export Date: 1 September 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Michael J Zelefsky
    670 Zelefsky
  2. Vincent Laudone
    69 Laudone
  3. Glenn Heller
    350 Heller
  4. Michael Morris
    341 Morris
  5. Peter T Scardino
    634 Scardino
  6. Abdelkrim Karim Touijer
    207 Touijer
  7. Joel Sheinfeld
    225 Sheinfeld
  8. Daniel D. Sjoberg
    156 Sjoberg
  9. Bernard Bochner
    359 Bochner
  10. James Eastham
    452 Eastham
  11. Howard Scher
    970 Scher
  12. Daniel C Danila
    101 Danila
  13. Sean Matthew McBride
    156 McBride
  14. Erica Simone Dayan
    4 Dayan