br These previous two points suggest that
These previous two points suggest that the observed AHR for OS associated with ADT use underestimates the true survival benefit of ADT for both Gleason 8 and 9–10 patients. However, our findings of significant interactions between ADT and Gleason score, which indicate that any survival advantage from the use of ADT is significantly weaker for Gleason 9–10 disease than Gleason 8 disease, should still stand. Lastly, our study is retrospective. The use of ADT was not randomized and may have been influenced by factors related to PCa (as discussed above), medical comorbidities not captured in the NCDB, and patient and provider preferences, which may have influenced survival outcomes. Specifically, patients with comorbidities may have been less likely to receive ADT given concerns about the lack of benefit from ADT in patients with comorbidities , while patients or providers who prefer using ADT may be more likely to pursue close post-treatment surveillance and aggressive therapies for recurrent disease. Since these covariates are not captured in the NCDB, they could not be adjusted for in multivariable models.
It is important to note that the AHR obtained from our analyses of the association between use of ADT and OS probably underestimates the true survival benefit from ADT for reasons described above. It may be that ADT still improves OS for certain Gleason 9–10 patients. However, we currently lack the tools necessary to predict which Gleason 9–10 patients have disease that would benefit from ADT and which patients harbor castration-resistant disease that requires novel anti-androgens or docetaxel. Genomics-based tools have[9T$DIF] shown[10T$DIF] [1T$DIF] promise in being able to predict response to ADT ; however, further development and validations of such tools are necessary before they can be incorporated into clinical practice.
In summary, in Amiloride HCL to the significant survival advan-tage of ADT for Gleason 8 PCa, our results suggest that Gleason 9–10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to intensification of therapy for Gleason 9–10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or doc-etaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings.
Author contributions: Paul Linh Nguyen had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Study concept and design: Yang, Nguyen.
Acquisition of data: Mahal, Muralidhar, Orio, Nguyen.
Analysis and interpretation of data: All authors.
Drafting of the manuscript: Yang, Nguyen.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Yang.
Obtaining funding: Nguyen.
Administrative, technical, or material support: Yang, Mahal, Muralidhar.
Financial disclosures: Paul Linh Nguyen 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, consultan-cies, honoraria, stock ownership or options, expert testimony, royalties, or patents filed, received, or pending), are the following:
Paul L. Nguyen reports personal fees from Ferring, Astellas, GenomeDx Inc, Dendreon, Nanobiotix, Augmenix, Bayer, and Blue Earth, as well as research support for clinical trials from Astellas and Janssen, which goes towards his affiliated institution. These financial relationships are all outside this submitted work. Felix Y. Feng reports personal fees from Medivation/Astellas, Ferring, GenomeDx Inc, Sanofi, Dendreon, Janssen, and EMD Serono and is a founder of PFS Genomics; these financial relationships are outside this submitted work. Neil E. Martin has received financial compensation for being a committee chair of Via Oncology, outside this submitted work. Quoc-Dien Trinh has received personal fees from Bayer and Astellas, outside this submitted work. Peter F. Orio has consulted for Augmenix, outside this submitted work. All other authors have no relevant conflicts of interest to disclose.
Funding/Support and role of the sponsor: This work was supported by the Prostate Cancer Foundation, Wood Family Foundation, the Baker Family, the Freeman Family, Fitz’s Cancer Warriors, David and Cynthia Chapin, the Frashure Family, Hugh Simons in honor of Frank and Anne Simons, the Campbell Family in honor of Joan Campbell, the Scott Forbes and Gina Ventre Fund, and a grant from an anonymous family foundation. The funders of this study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.