The document discusses treatment strategies for hormone naive prostate cancer, including metastatic and non-metastatic disease. It summarizes several key trials comparing androgen deprivation therapy alone versus combinations with docetaxel or abiraterone/prednisone. For metastatic disease, combination therapy provided a survival benefit, especially for patients with high volume/high risk disease, but minimal benefit was seen for low volume/low risk disease. For non-metastatic PSA recurrence, early androgen deprivation provided no benefit over delayed treatment initiation.

1. Hormone Naive Prostate cancer

2. INTRODUCTION
Hormone naïve advanced prostate cancer is subdivided into two disease states:
biochemical recurrence and traditional M1 (metastatic) prostate cancer and
characterized by no prior hormonal therapy or androgen deprivation therapy
(ADT)
Moul JW et al Asian Journal of Andrology (2015) 17, 929–935

3. Hormone Naive metastatic
Prostate Cancer

4. Androgen-Deprivation Therapy + Docetaxel -CHAARTED
Sweeney CJ, et al. N Engl J Med. 2015;373(8):737-746

5. Androgen-Deprivation Therapy + Docetaxel CHAARTED
Sweeney CJ, et al. N Engl J Med. 2015;373(8):737-746

6. Androgen-Deprivation Therapy + Docetaxel CHAARTED
Patients with High Volume Disease Patients with low Volume Disease
Sweeney CJ, et al. N Engl J Med. 2015;373(8):737-746

7. STAMPEDE: Results
James ND, et al. Lancet. 2016;387(10024):1163-1177
Androgen-Deprivation Therapy + Docetaxel

8. Androgen-Deprivation Therapy + Docetaxel
STAMPEDE: Results
James ND, et al. Lancet. 2016;387(10024):1163-1177

9. ADT + Docetaxel in Castration-Naïve mPCA
• ADT + DOC superior in terms of OS and rPFS
 CHAARTED: high-volume disease with 17 months OS benefit low-volume
disease without benefit
 STAMPEDE no stratification low/high risk OS benefit only in M1, not in M0

10. Androgen-Deprivation Therapy + Abiraterone/Prednisone:
LATITUDE
Fizazi K, et al. N Engl J Med. 2017;377(4):352-360

11. Androgen-Deprivation Therapy + Abiraterone/Prednisone:
LATITUDE
Fizazi K, et al. N Engl J Med. 2017;377(4):352-360

12. Androgen-Deprivation Therapy + Abiraterone/Prednisone:
LATITUDE
Fizazi K, et al. N Engl J Med. 2017;377(4):352-360

13. Androgen-Deprivation Therapy + Abiraterone/Prednisone:
STAMPEDE
James ND, et al. N Engl J Med. 2017;377(4):338-351.

14. Androgen-Deprivation Therapy + Abiraterone/Prednisone:
STAMPEDE
James ND, et al. N Engl J Med. 2017;377(4):338-351.

15. ADT + Abiraterone/P in Hormone-Naïve mPCA
• ADT + A/PP superior in terms of OS and rPFS
 LATITUDE: 3-year OS 66% vs 49% 3-year rPFS 33 months vs
14.8 months
 STAMPEDE 3-year OS 83 vs 76% 3-year FFS 75 vs 45%

16. ADT + Abiraterone/P
Versus
ADT + Docetaxel in Hormone-
Naïve mPCA

17. Metastatic Burden in Newly Diagnosed Hormone-Naïve
Metastatic Prostate Cancer: Comparing Definitions of
CHAARTED and LATITUDE Trials CRPC-FS
BuelensS, et al. Urol Oncol. 2018 January 11. [Epub ahead of print]
LVD, low-volume disease; HVD, high-volume disease; LRD, low-risk disease; HRD,
high-risk disease
40 vs11
months
40 vs11
months

18. Metastatic Burden in Newly Diagnosed Hormone-Naïve
Metastatic Prostate Cancer: Comparing Definitions of
CHAARTED and LATITUDE Trials -overall survival
LVD, low-volume disease; HVD, high-volume disease; LRD, low-risk disease; HRD,
high-risk disease NR, not reached
BuelensS, et al. Urol Oncol. 2018 January 11. [Epub ahead of print]
NR vs 51 months
NR vs 51 months

19. Metastatic Burden in Newly Diagnosed Hormone-Naïve
Metastatic Prostate Cancer: Comparing CHAARTED and
LATITUDE Trials
BuelensS, et al. Urol Oncol. 2018 January 11. [Epub ahead of print]

20. ADT + Abiraterone/P vs ADT + Docetaxel in Hormone-
Naïve mPCA
• Equal oncologic efficacy in terms of OS and rPFS
• Equal oncologic efficacy in high-volume/high-risk disease as compared to ADT
• Minimal oncologic benefit in low-volume/low-risk disease as compared to ADT
BuelensS, et al. Urol Oncol. 2018 January 11. [Epub ahead of print]

21. Annals of Oncology 29: 1249–1257, 2018

22. Network meta-analysis
Annals of Oncology 29: 1249–1257, 2018

23. Overall survival. Forest plot of network and pairwise
estimates of treatment effects [all treatments compared with
androgen-deprivation therapy (ADT) alone
Annals of Oncology 29: 1249–1257, 2018

24. Failure Free survival. Forest plot of network and pairwise
estimates of treatment effects [all treatments compared with
androgen-deprivation therapy (ADT) alone
Annals of Oncology 29: 1249–1257, 2018

25. Indirect comparison of Overall Survival and Failure Free
Survival of the two most effective treatment combination
Annals of Oncology 29: 1249–1257, 2018
A,Overall Survival; B,Failure Free Survival.

26. • AAP appears to be the most effective treatment,but it is not clear to what
extent and whether this is due to a true increased benefit with AAP or to the
variable features of the individual trials.
• To fully account for patient variability across trials, changes in prognosis or
treatment effects over time, and the potential impact of treatment on
progression, a network meta-analysis based on individual participant data is
currently in development
Annals of Oncology 29: 1249–1257, 2018

27. Ongoing Trial

28. PEACE I European phase III trial of Abiraterone in patients
with newly diagnosed metastatic Prostate cancer

29. NON METATSTATIC PROSTATE
CANCER
PSA ONLY RECURRENCE

30. Moul JW, et al. J Urol. 2004;171(3):1141-

31. Early vs Delayed Hormonal Therapy PSA-Only Recurrence
of Prostate Cancer After Radical Prostatectomy
Pathologic Gleason >7
or PSADT ≤ 12 months
Pathologic Gleason >7
or PSADT ≤ 12 months
Moul JW, et al. J Urol. 2004;171(3):1141-

32. Moul JW, et al. J Urol. 2004;171(3):1141-
Early vs Delayed Hormonal Therapy PSA-Only Recurrence
of Prostate Cancer After Radical Prostatectomy
EarlyADT (PSA ≤5 ng/mL) without
impact on metastases-free survival

33. Androgen Deprivation Therapy + Abiraterone/Prednisone
STAMPEDE
James ND, et al. N Engl J Med. 2017;377(4):338-351

34. Conclusion
• ADT + docetaxel or ADT+AA/P are regimes with proven survival benefit
• Survival benefit is most apparent in high-volume/high-risk disease
• No significant survival benefit in low-risk/low-volume disease
• Consider comorbidities & treatment-associated AEs to select the most
appropriate strategy