Efficacy of Local Treatment in Prostate Cancer Patients with Clinically Pelvic Lymph Node-positive Disease at Initial Diagnosis

Thomas Seisen; Malte W Vetterlein; Patrick Karabon; Tarun Jindal; Akshay Sood; Luigi Nocera; Paul L Nguyen; Toni K Choueiri; Quoc-Dien Trinh; Mani Menon; Firas Abdollah

doi:10.1016/j.eururo.2017.08.011

Efficacy of Local Treatment in Prostate Cancer Patients with Clinically Pelvic Lymph Node-positive Disease at Initial Diagnosis

Eur Urol. 2018 Mar;73(3):452-461. doi: 10.1016/j.eururo.2017.08.011. Epub 2017 Sep 8.

Authors

Affiliations

¹ Center for Outcomes Research, Analytics and Evaluation, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA; Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
² Center for Outcomes Research, Analytics and Evaluation, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA.
³ Department of Radiation Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
⁵ Division of Urological Surgery and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁶ Center for Outcomes Research, Analytics and Evaluation, Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, USA. Electronic address: firas.abdollah@gmail.com.

PMID: 28890245
DOI: 10.1016/j.eururo.2017.08.011

Abstract

Background: There is limited evidence supporting the use of local treatment (LT) for prostate cancer (PCa) patients with clinically pelvic lymph node-positive (cN1) disease.

Objective: To examine the efficacy of any form of LT±androgen deprivation therapy (ADT) in treating these individuals.

Design, setting, and participants: Using the National Cancer Database (2003-2011), we retrospectively identified 2967 individuals who received LT±ADT versus ADT alone for cN1 PCa. Only radical prostatectomy (RP) and radiation therapy (RT) were considered as definitive LT.

Intervention: LT±ADT versus ADT alone.

Outcome measurements and statistical analysis: Instrumental variable analyses (IVA) were performed using a two-stage residual inclusion approach to compare overall mortality (OM)-free survival between patients who received LT±ADT versus ADT alone. The same methodology was used to further compare OM-free survival between patients who received RP±ADT versus RT±ADT.

Results and limitations: Overall, 1987 (67%) and 980 (33%) patients received LT±ADT and ADT alone, respectively. In the LT±ADT group, 751 (37.8%) and 1236 (62.2%) patients received RP±ADT and RT±ADT, respectively. In IVA, LT±ADT was associated with a significant OM-free survival benefit (hazard ratio=0.31, 95% confidence interval [CI]=0.13-0.74, p=0.007), when compared with ADT alone. At 5 yr, OM-free survival was 78.8% (95% CI: 74.1-83.9%) versus 49.2% (95% CI: 33.9-71.4%) in the LT±ADT versus ADT alone groups. When comparing RP±ADT versus RT±ADT, IVA showed no significant difference in OM-free survival between the two treatment modalities (hazard ratio=0.54, 95% CI=0.19-1.52, p=0.2). Despite the use of an IVA, our study may be limited by residual unmeasured confounding.

Conclusions: Our findings show that PCa patients with clinically pelvic lymph node-positive disease may benefit from any form of LT±ADT over ADT alone. While not necessarily curative by itself, the use of RP or RT could be the first step in a multi-modality approach aiming at providing the best cancer control outcomes for these individuals.

Patients summary: We examined the role of local treatment for clinically pelvic lymph node-positive prostate cancer. We found that the delivery of radical prostatectomy or radiation therapy may be associated with an overall mortality-free survival benefit compared with androgen deprivation therapy alone.

Keywords: Castration; Lymph nodes; Prostate neoplasms; Prostatectomy; Radiotherapy.