Editing Management of Localized Prostate Cancer (section)

== Management of High-Risk Localized Prostate Cancer ==

* 15% of patients with localized disease have high-risk prostate cancer[https://pubmed.ncbi.nlm.nih.gov/20124165/]
* '''Management'''
** Historically, treated with ADT alone, radiation, or radiation + ADT
** '''Options:'''
**#'''Clinical trial'''
**#'''Radical prostatectomy'''
**#'''Radiation + ADT'''
**Radical prostatectomy
*** Potential advantages
**** Local control and debulking may improve the efficacy of sequential therapy (radiation therapy or ADT)
**** Local control and debulking may prevent clinical complications, such as hematuria and obstruction
*** Potential disadvantages
**** Overtreatment and increased morbidity, in patient that will ultimately get radiation + ADT, or already has micrometastatic disease
*** Outcomes
****Limited data
*****Retrospective cohort studies
****** Population: 176 patients who underwent radical prostatectomy for clinical stage T3 prostate cancer, 36% of which received neoadjuvant hormonal therapy
****** Results
******* Median follow-up: 6.4 years
******* Biochemical recurrence
******** 5-year biochemical recurrence-free survival: 48%
******** 10-year biochemical recurrence-free survival: 44%
******** 17% of patients with BCR treated with salvage radiation
******** 77% of patients with BCR treated with hormonal therapy
******* Cancer-specific survival
******** 5-year cancer-specific survival 94%
******** 10-year cancer-specific survival 85%
****** [https://pubmed.ncbi.nlm.nih.gov/16813890 Carver, Brett S., et al.] "Long-term outcome following radical prostatectomy in men with clinical stage T3 prostate cancer." ''The Journal of urology'' 176.2 (2006): 564-568.
******Population: 24,407 high-risk patients from SEER. Using propensity score-matching, 7,363 RP patients compared to 7,363 EBRT patients
******Results
*******5-year cancer-specific survival improved in RP compared to EBRT (97.7% RP vs. 95.9% EBRT)
******[https://pubmed.ncbi.nlm.nih.gov/34555930/ Chierigo, Francesco, et al.] "Survival after radical prostatectomy versus radiation therapy in high-risk and very high-risk prostate cancer." ''The Journal of Urology'' 207.2 (2022): 375-384.
****Combination therapy
*****Neoadjuvant ADT may improve outcomes
******Phase II trials demonstrate that pathologic complete response achieved in 4-10% of patients, and minimal residual disease in 17-30% of patients.
******Phase III trial ([https://clinicaltrials.gov/ct2/show/NCT03767244 PROTEUS]) underway
*****Neoadjuvant chemotherapy 
******PUNCH trial evaluated neoadjuvant docetaxel + ADT and found no significant difference in the primary outcome of 3-year biochemical progression-free survival
*****Adjuvant ADT
******Controversial
******[https://clinicaltrials.gov/ct2/show/NCT01442246 AFU-GETUG-20] trial evaluating adjuvant leuprolide for 2 years after radical prostatectomy
******ERADICATE trial will evaluate adjuvant darolutamide after radical prostatectomy
**Radiation
***Combination radiation + ADT is a standard of care option for high-risk prostate cancer, with several trials demonstrating improved outcomes with combination therapy compared to monotherapy
***Optimal duration of therapy not established
****2017 AUA Guidelines on Localized Prostate Cancer recommend 24-36 months
***Combination radiation + second-generation anti-androgen trials underway (ATLAS apalutamide and ENZARAD enzalutamide)
***