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Gleason score associated with time to development of neuroendocrine prostate cancer
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Gleason scores among patients with conventional prostatic adenocarcinoma was significantly associated with time to development of treatment-related neuroendocrine prostate cancer, according to study results.
Survival after diagnosis of neuroendocrine prostate cancer was associated with treatment type and the number of organs with metastatic disease, results also showed.
Hai Tao Wang, MD, PhD, of the Tianjin Cancer Hospital and Institute in Tianjin, China, and colleagues conducted a literature review of 54 studies to identify risk factors associated with treatment-related neuroendocrine prostate cancer. The analysis included 123 patients who had a prior history of prostate adenocarcinoma and who had confirmed neuroendocrine prostate cancer (median age at initial diagnosis, 67 years).
The median time to development of neuroendocrine prostate cancer after initial prostate cancer diagnosis was 20 months (range, 1-144). Results of a multivariate analysis indicated a Gleason score ≥8 was the only factor significantly associated with a shorter time to neuroendocrine prostate cancer development (HR=1.66 vs. Gleason score <8; 95% CI, 1.04-2.64).
Median survival after neuroendocrine prostate cancer diagnosis was 7 months (range, 0.5-63).
Multivariate analyses indicated patients who had three or more organs with metastatic disease experienced shorter survival compared with patients who had fewer than three involved organs (HR=3.31; 95% CI, 1.62-6.76).
Survival improved among patients who underwent radiation therapy (HR=0.66; 95% CI, 0.45-0.96), chemotherapy (HR=0.38; 95% CI, 0.17-0.85), or chemotherapy and radiation therapy (HR=0.29; 95% CI, 0.11-0.76) compared with patients who only received palliative therapy.
“Treatment-related neuroendocrine prostate cancer is an often under-recognized late manifestation of prostate adenocarcinoma with poor prognosis,” Wang and colleagues concluded. “Our study found that Gleason score was the only independent factor contributing to time to neuroendocrine prostate cancer. Once neuroendocrine prostate cancer is diagnosed, type of treatment and number of metastatic organs were the most important factors related to survival. Additional studies are necessary to identify specific molecular features of the disease or treatment that may be associated with treatment-associated neuroendocrine prostate cancer.”
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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Neeraj Agarwal, MD
The article by Wang and colleagues is timely given the increasing recognition that treatment-associated neuroendocrine prostate cancer may progress from conventional prostatic adenocarcinoma following treatment with novel androgen pathway-targeting agents. The authors describe risk factors related to survival after neuroendocrine prostate cancer diagnosis, as well as time from initial diagnosis of prostate cancer to development of neuroendocrine prostate cancer. The median time to development of neuroendocrine prostate cancer was 20 months, and the median survival after neuroendocrine prostate cancer diagnosis was 7 months. Gleason score was the only independent factor contributing to time to development of neuroendocrine prostate cancer. Once neuroendocrine prostate cancer is diagnosed, the number of organs with metastatic disease and the type of treatment were the most important factors related to survival.
The development of treatment-associated neuroendocrine prostate cancer is associated with rapidly progressive castration-resistant prostate cancer with disproportionately low PSA values, visceral metastases, paraneoplastic syndrome and/or high levels of serum neuroendocrine markers. The current mainstay of treatment is platinum-based chemotherapy and the prognosis remains poor, as reported by Wang and colleagues.
The transformation of prostatic adenocarcinoma to neuroendocrine prostate cancer has been proposed to occur as a mechanism of treatment resistance, driven by the selection pressure of androgen deprivation therapy and the novel drugs targeting androgen synthesis and androgen receptor. This is supported by the observations that neuroendocrine prostate cancer and adenocarcinoma components often occur simultaneously, and in the majority of these cases, a concordance for ERG rearrangements was present in both components. However, further investigation is needed to determine whether these two components emerge from a common stem cell, or whether neuroendocrine prostate cancer evolves from the conventional adenocarcinoma.
Recent reports that suggest aurora kinase A and N-Myc are frequently amplified in treatment-associated neuroendocrine prostate cancer and are involved in neuroendocrine differentiation of prostate cancer provide the rationale for development of molecularly targeted therapies for these pathways. Given the high degree of tumor heterogeneity in treatment-associated neuroendocrine prostate cancer, it is likely that additional molecular pathways will be identified in the near future, and that the combinatorial regimens that target these specific pathways in a given neuroendocrine prostate cancer tumor will have the most potential to provide long-term responses and a meaningful improvement in survival.
For more information:
- Beltran H. J Clin Oncol. 2012;30:e386-e389.
- Lotan TL. Mod Pathol. 2011;24:820-828.
- Beltran H. Cancer Discov. 2011;1:487-495.
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