Neuroendocrine prostate cancer (NEPC) encompasses various clinical contexts, ranging from the de novo presentation of small cell prostatic carcinoma to a treatment-emergent transformed phenotype that arises from typical adenocarcinoma of the prostate. The development of resistance to potent androgen receptor signaling inhibition may be associated with the emergence of aggressive phenotype, advanced castration-resistant NEPC. Clinically, small cell prostate cancer and NEPC are often manifested by the presence of visceral or large soft tissue metastatic disease, a disproportionately low serum prostate-specific antigen level relative to the overall burden of disease, and a limited response to targeting of the androgen signaling axis. These tumors are often characterized by loss of androgen receptor expression, loss of retinoblastoma tumor suppressor copy number or expression, amplification of Aurora kinase A and N-Myc, and activation of the PI3K pathway. However, a consensus phenotype-genotype definition of NEPC has yet to emerge, and molecularly based biomarkers are needed to expand on traditional morphologic and immunohistochemical markers of NEPC to fully define the spectrum of this aggressive, androgen receptor-independent disease. Emerging studies implicate a shared clonal origin with prostatic adenocarcinoma in many cases, with the adaptive emergence of unique cellular programming and gene expression profiles. Ongoing clinical studies are focused on developing novel targeted therapeutic approaches for this high-risk, lethal subset of disease, to improve on the limited durations of response often observed with traditional platinum-based chemotherapy.
Rahul Aggarwal, Tian Zhang, Eric J. Small, and Andrew J. Armstrong
Arif Kamal, Tian Zhang, Steve Power, and P. Kelly Marcom
Background: The American Board of Internal Medicine Foundation's Choosing Wisely initiative aims to reduce unnecessary advanced imaging for early-stage breast cancer (ESBC). Additionally, NCCN Clinical Practice Guidelines in Oncology for Breast Cancer permit such images when oncologists perceive clinical clues of advanced disease. The utility of advanced imaging in ESBC is not known. Patients and Methods: We analyzed all patients with ESBC from January 2010 to June 2012 at a large tertiary cancer center. Early-stage was defined as stage IIb or less. We included advanced imaging within 60 days after diagnosis. Three independent reviewers manually abstracted a sample of charts to determine reason for ordering. Results: A total of 1,143 ESBC cases were identified; 21.8% of which had at least one advanced imaging procedure performed. Imaging modalities varied widely (38% CT, 21% PET, 34% bone scans, and 6% MRI). Patients who underwent advanced imaging were more likely to have triple-negative disease, be younger (age <50 years), and have higher stage disease (stage IIb vs ≤ stage IIa; all P<.001). A total of 100 cases (40%) were abstracted; 5 were excluded due to bilateral disease. Of the 95 cases remaining, 62% of the imaging studies were performed for staging, 17% for significant concurrent disease, and 22% for findings atypical of ESBC. Of the studies performed for staging, 15% produced clinically meaningful findings. Overall, 45% of studies were ordered for suspicious findings, complex history, or produced a meaningful result. Conclusions: Of patients with ESBC, 21.8% had at least one advanced imaging procedure within 60 days of diagnosis; almost half were clinically useful. Chart abstraction helped clarify intent. Conversations between clinicians and patients are needed to balance patient preferences and clinician judgment.