This document discusses several predictive models and nomograms for prostate cancer outcomes: - The CAPRA nomogram predicts outcomes after radical prostatectomy using clinical factors. - The J-CAPRA nomogram was designed for patients receiving primary androgen deprivation therapy and predicts cancer progression and mortality. - Nomograms have been developed to predict survival for patients with metastatic castration-resistant prostate cancer using PSA kinetics and other clinical variables. - Additional nomograms aim to predict outcomes after specific therapies like docetaxel or abiraterone. Prospective validation of these tools is still needed to help guide treatment decisions.

1. April 7-9, 2011 Memorial Sloan-Kettering Cancer Center New York, US

2. Nomograms currently represent one of the most accurate and discriminating tools for predicting outcomes in patients with Pca Despite limitations, predictive tools can provide individualized, evidence-based estimates for a number of PCa endpoints, thereby helping in the complex decision-making process. Predictive tools can facilitate medical decision-making by showing patients tailored predictions of their outcomes with various alternatives There are no prospective randomized studies that clearly demonstrate that the use of prediction tools improve patient care or reduce patient anxiety, decisional conflict, or regret PREDICTIVE TOOLS AND NOMOGRAMS

3. PREDICTING MODELS FOR ADVANCED HSPC

4. Three polymorphisms in separate genes ( CYP19A1, HSD3B1, and HSD17B4) were significantly ( P .01) associated with time to progression (TTP) during ADT,

7. CAPRA (Cancer of the Prostate Risk Assessment ) Predict pathological and biochemical outcomes after radical prostatectomy, predict metastases, predict prostate cancer–specific mortality, and all-cause mortality. CAPRA scores were calculated at diagnosis from the PSA level, Gleason score, percentage of biopsy cores that were positive for cancer, clinical tumor stage, and age at diagnosis. Each single-point increase in the CAPRA score was associated with increased bone metastases cancer-specific mortality and all-cause mortality. Patients with clinically localized prostate cancer who were managed with one of five primary modalities, the CAPRA score predicted clinical prostate cancer endpoints with good accuracy

8. The first instrument that uses information available at time of diagnosis to predict accurately the development of metastases, cancer-specific mortality, and all-cause mortality, irrespective of primary treatment

9. Comparison of risk features between large disease registries from the United States and Japan, aiming to build and validate a risk prediction model applicable to primar androgen deprivation therapy (PADT ) patients. Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments J-CAPRA—scored 0 to 12 based on Gleason score, PSA level, and clinical stage—predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84. Applicable to those with both localized and advanced disease, and performs well in diverse populations

10. A PSA of 4 ng/mL or less after 7 months of AD is a strong predictor of survival.

11. PSA-P, defined as an increase of 25% greater than the nadir and an absolute increase of at least 2 or 5 ng/mL, predicts OS in HSPC and CRPC and may be a suitable end point for phase II studies in these settings.

12. PREDICTING MODELING FOR ADVANCED CRPC

13. Expected survival models based on: performance status, presence of visceral metastases, baseline prostate-specific antigen (PSA), advanced primary Gleason sum, hemoglobin, LDH, albumin, and Alk P (Smaletz 2002, Halabi 2003) Prognostic analyses limited: inclusion of various types of noncytotoxic therapy and no patients with docetaxel-based therapy Can only be used for stratification of patients in phase III trials Predictive models as an aid to decision making -10/2007-

14. Halabi et al., JCO 21:1232-7, 2003 Useful to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials

16. Integrating PSA Kinetics

18. Something new after 2008 ?

19. Nomogram Development PSADT has emerged as an easily obtainable and clinically relevant prognostic marker in several stages of prostate cancer,including pre-prostatectomy, pre-radiation therapy, rising PSA after local therapy, nonmetastatic CRPC, and... --------  in metastatic CRPC

20. Survival by PSADT 0.25 0.50 0.75 1.00 Survival (%) 0 5 10 15 20 25 30 35 40 45 50 Survival (months) PSADT <1 month PSADT 1–2 months Log-rank p<0.001 0 Eisenberger M, et al. J Clin Oncol 2007; 25: abstract # 5058 & PSADT is an Independent Risk Factor for Death in HRPC PSADT 4–6 months PSADT >6 months PSADT 2–3 months

21. Purpose: To develop a prognostic model and nomogram using baseline clinical variables to predict death among men with metastatic hormone-refractory prostate cancer (HRPC)

22. Nomogram for predicting 1-, 2-, and 5-year survival (HRPC) incorporating PSA kinetics

23. Nomograms provide the clinician with an overall assessment of a patient’s prognosis, but do not directly impact on decisions for the ideal starting point for docetaxel-based therapy, given that all patients in these nomograms had received therapy Additional factors are also likely to contribute to OS (covered in other nomograms,) - LDH and albumin, serum biomarkers for vascular endothelial growth factor and other cytokines, CTCs, and other unmeasured prognostic factors.

24. SQUEEZING TAX 327 DATA BASE

25. Simple ways to predict survival

26. They analyzed predictors of postprogression survival according to both prechemotherapy and postchemotherapy variables with adjustment for potential confounders. The nomogram may also improve the information delivered to men with CRPC about prognosis. The prognostic factors identified in this study include both known prechemotherapy factors and type of progression and duration of chemotherapy. Predicting post chemo survival

28. They investigated pre-treatment factors that predicted a > 30% PSA decline (30% PSAD) within 3 months of starting chemotherapy, Assessed performance of a risk group classification in predicting PSA declines and overall survival (OS) in men with mCRPC. Four independent risk factors predicted 30% PSAD: pain, visceral metastases, anemia and bone scan progression. Risk groups (good: 0–1 factors, intermediate: 2 factors and poor: 3–4 factors) were developed  may facilitate evaluation of new systemic regimens warranting definitive testing in comparison with docetaxel and prednisone

29. Kaplan–Meier estimates of overall survival according to risk group classification. Median survival figures are represented in the legend

30. Normalization of ALP remained prognostic for OS after adjusting for PSA decline > 30% by day 90 (HR 0.79, 95% CI 0.65– 0.97, P 0.022).

31. In patients with CRPC, the association of measurable tumor responses with overall survival (OS) is unknown Four hundred twelve patients enrolled on the TAX327 trial had measurable tumors (CR/PR, 9.0%) PRs demonstrated longer median OS (29.0 months) than patients with SD (22.1 months) or those with PD (10.8 months) or those who were not assessed (12.7 months) Radiologic response remained a significant but modest post-treatment prognostic factor for OS after adjusting for treatment, pain response, and 30% PSA decline (P = .009)

32. The available PCa nomograms have been adapted for use on personal digital assistants and personal computers to facilitate their integration into daily clinical practice and research. Many of the nomograms can be found either : Memorial-Sloan-Kettering Cancer Center (www.nomograms.org) or the University of Montreal (www.nomogram.org) websites Fox Chase Industry Sponsored tools

42. Predictive models in CRPC as an aid to decision making -04/2011- Docetaxel era The choice between docetaxel and secondary hormonal therapy still relegated to clinical judgment . No prospective trial is under way or planned Predictive models to determine a patient’s pretherapy prognosis ( nomograms ) and posttherapy (Armstrong) Smaletz, Halabi, Svatek, Armstrong May prove useful in the decision point of chemotherapy versus non-chemotherapeutic approaches (require prospective validation)

43. Predictive models in CRPC as an aid to decision making -04/2011- Abiraterone and Cabazitaxel era The choice between docetaxel and new hormonal therapy will be relegated to clinical judgment No prospective trial is under way or planned (abiraterone, MDV vs docetaxel or cabazitaxel ) using nomograms Need to have predictive nomograms for decision making for pre/postdocetaxel , for abiraterone/MDV and for cabazitaxel