Lymph node metastases after radical prostatectomy (RP) are associated with increased risk of recurrence and poor survival. Despite decades of experience, the optimal management (timing and choice of therapy) remains unclear since a number of management strategies are utilized, including observation with salvage treatment or lifelong adjuvant androgen deprivation therapy (ADT) alone or with external beam radiation therapy (EBRT).
According to Touijer et al, adjuvant ADT with whole pelvic EBRT is associated with better overall survival than observation or adjuvant ADT (European Urology Oct. 16, 2017 [Epub ahead of print]).
The authors performed a retrospective analysis comparing survival outcomes of LN+ patients after RP performed at three tertiary care centers between 1988 and 2010. The type and timing of treatment were driven by local practice patterns at each institution. They identified 1,338 patients who were LN+ after RP who were either observed or received salvage therapy (387, 28%), adjuvant lifelong ADT (676, 49%), or adjuvant EBRT with ADT (325, 23%). Median follow-up time was 69 months among survivors, with 368 men followed for more than 10 years.
The observation group consisted of no treatment until biochemical recurrence, which was defined variably by each institution as PSA level of >0.1, >0.2, or >0.4 ng/mL. After biochemical recurrence, the most commonly used treatments were ADT alone (72%), followed by salvage EBRT (13%) and ADT plus EBRT (8.9%).
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Adjuvant ADT consisted of either bilateral orchiectomy or luteinizing hormone-releasing hormone agonist used alone as lifelong therapy. When combined with EBRT, the median duration of ADT was 5.9 years, with 75% of men receiving >3 years. Median dose of EBRT (3-D conformal or IMRT) was 68 Gy.
ADT had better cancer-specific survival compared to observation (HR: 0.64, p=.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, p=.003) compared with observation, resulting in similar overall survival between ADT and observation (HR: 0.90, 95% CI: 0.65–1.25, p=.5). Lifelong adjuvant ADT was associated with an increased risk of death from other causes (cardiac, metabolic), thus wiping out any oncologic benefit from lifelong adjuvant ADT.
Radiation therapy with ADT was associated with better overall survival than ADT alone (HR: 0.46, p<.0001) or observation (HR: 0.41, p<.0001). Patients with higher risk features (T4, high grade, positive margins) derived the most benefit from combined adjuvant EBRT+ADT than lower risk patients. There was no significant difference in overall survival between men treated with adjuvant ADT and those on observation.
Recurrence patterns following prostatectomy are informative in that pN+ is not necessarily a systemic process, since 30%-40% of men will not experience recurrence for >5 years. This study points to the clinically heterogeneous nature of pN+ cohort and to the potential survival benefits derived from further loco-regional cancer control with whole pelvic EBRT after radical prostatectomy.