Assessment of a prognostic model, PSA metrics and toxicities in metastatic castrate resistant prostate cancer using data from Project Data Sphere (PDS).
BACKGROUND
Prognostic models in metastatic castrate resistant prostate cancer (mCRPC) may have clinical utility. Using data from PDS, we aimed to 1) validate a contemporary prognostic model (Templeton et al., 2014) 2) evaluate prognostic impact of concomitant medications and PSA decrease 3) evaluate factors associated with docetaxel toxicity.


METHODS
We accessed data on 2,449 mCRPC patients in PDS. The existing model was validated with a continuous risk score, time-dependent receiver operating characteristic (ROC) curves, and corresponding time-dependent Area under the Curve (tAUC). The prognostic effects of concomitant medications and PSA response were assessed by Cox proportional hazards models. One year tAUC was calculated for multivariable prognostic model optimized to our data. Conditional logistic regression models were used to assess associations with grade 3/4 adverse events (G3/4 AE) at baseline and after cycle 1 of treatment.


RESULTS
Despite limitations of the PDS data set, the existing model was validated; one year AUC, was 0.68 (95% CI 95% CI, .66 to .71) to 0.78 (95%CI, .74 to .81) depending on the subset of datasets used. A new model was constructed with an AUC of .74 (.72 to .77). Concomitant medications low molecular weight heparin and warfarin were associated with poorer survival, Metformin and Cox2 inhibitors were associated with better outcome. PSA response was associated with survival, the effect of which was greatest early in follow-up. Age was associated with baseline risk of G3/4 AE. The odds of experiencing G3/4 AE later on in treatment were significantly greater for subjects who experienced a G3/4 AE in their first cycle (OR 3.53, 95% CI 2.53-4.91, p < .0001).


CONCLUSIONS
Despite heterogeneous data collection protocols, PDS provides access to large datasets for novel outcomes analysis. In this paper, we demonstrate its utility for validating existing models and novel model generation including the utility of concomitant medications in outcome analyses, as well as the effect of PSA response on survival and toxicity prediction.
Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Bethany
B
Pitcher
Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Leila
L
Khoja
Department of Urologic Oncology, University Health Network, Toronto, Ontario, Canada.
Robert J
RJ
Hamilton
Project Data Sphere LLC, Cary, North Carolina, United States of America.
Kald
K
Abdallah
Department of Biostatistics, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Melania
M
Pintilie
Department of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.|Department of Medical Oncology, Kinghorn Cancer Centre, St Vincent's Hospital, Sydney, New South Wales, Australia.
Anthony M
AM
Joshua
D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D019540:Area Under Curve; D052246:Cyclooxygenase 2 Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D018450:Disease Progression; D000077143:Docetaxel; D006495:Heparin, Low-Molecular-Weight / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008687:Metformin / Q000009:adverse effects / Q000627:therapeutic use; D008962:Models, Theoretical; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy / Q000401:mortality; D012372:ROC Curve; D043823:Taxoids / Q000009:adverse effects* / Q000627:therapeutic use*; D016896:Treatment Outcome; D014859:Warfarin / Q000009:adverse effects / Q000627:therapeutic use
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D006495:Heparin, Low-Molecular-Weight; D043823:Taxoids; D000077143:Docetaxel; D014859:Warfarin; D008687:Metformin; D017430:Prostate-Specific Antigen