Editing Prostate Cancer: Management of Locally Advanced Prostate Cancer (section)

=== Management of pN1 after radical prostatectomy ===
*Heterogeneous natural history
**Up to 30% of patients may remain free of disease long-term following surgery without further therapy.
*'''Options (3)'''[https://www.nccn.org/guidelines §]
*# '''Observation'''
*#'''ADT'''
*# '''EBRT + ADT'''
** '''Observation'''
*** Retrospective cohort study of 369 patients with pN1 disease found that 28% of males remained free from biochemical recurrence at 10 years.[https://pubmed.ncbi.nlm.nih.gov/23619390/ §] 
**'''ADT'''
*** '''Eastern Cooperative Oncology Group (ECOG) 7887/3886 (Messing et al. 1999 NEJM)'''
**** '''Population: 98 men with pelvic lymph node metastases after RP (cT1-T2 disease) + LND'''
**** '''Randomized to immediate (adjuvant) or delayed (detection of distant metastases or symptomatic recurrences) ADT'''
**** '''Results:'''
***** '''Median follow-up 11.9 years'''
***** '''Immediate ADT significantly improved disease-free survival, cancer-specific survival, and OS'''
**** '''Interpretation: Adjuvant ADT in patients found to have nodal metastases after radical prostatectomy and pelvic lymph node dissection is associated with improved survival'''
**** Messing, Edward M., et al."Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy." ''The lancet oncology'' 7.6 (2006): 472-479. [Original publication 1999 NEJM]
***** Trial criticisms:
****** Underpowered: the study was designed to enroll 240 patients, yet only enrolled 100
****** Gleason grading was not centralized and the absence of a correlation between histologic grade and survival in the trial suggests an imbalance may exist.
****** Those on delayed ADT experienced disease progression and prostate cancer death that was much more rapid than would have been expected from contemporary N+ patients
**** The magnitude of the difference observed in the ECOG 3886 study has not been seen in larger similar—but not identical—patient populations.
***** EORTC trial (Schröder et al, 2004)
****** Population: 302 pN1-3M0 prostate cancer without local treatment of the primary tumor
****** Randomized to immediate vs. delayed ADT
****** Results:
******* Median follow-up 13 years
******* No significant difference in OS (7.6 vs. 6.1 years)
******* 10-year cumulative incidence of death from prostate cancer was 55.6% in the delayed ADT group versus 52.1% in the immediate ADT group (Schröder et al, 2009); 20.8 patients would need to be treated with immediate ADT to spare one life at 5 years and 28.6 to spare one life at 10 years.
** '''EBRT + ADT'''
*** Retrospective cohort studies from the National Cancer Database found that in patients with lymph node metastases after radical prostatectomy, EBRT + ADT improved biochemical recurrence-free, cancer-specific, and overall survival, compared to ADT alone.
*'''Patients should be risk-stratified based on pathologic variables (particularly the number of positive nodes identified) and postoperative PSA to guide use of secondary therapy.[https://pubmed.ncbi.nlm.nih.gov/35536144/]'''
**If undetectable post-operative PSA, consider surveillance with the option of early salvage should the patient experience biochemical recurrence. Adjuvant therapies (e.g. ADT or radiation) are alternatives.
**If detectable post-operative PSA, salvage therapy with ADT is recommended.
***The optimal timing (post-operative vs. at biochemical recurrence) of initiating ADT for patients with pN1 remains unknown.