The oncologic role of local treatment in primary metastatic prostate cancer.

PURPOSE: To determine the oncologic benefit or otherwise of local treatment of the prostate in patients with primary metastatic prostate cancer. METHODS: A review of the literature was performed in April 2014 using the Medline/PubMed database. Studies were identified using the search terms "prostate cancer," "metastatic," "metastasis," "high risk," "radiation therapy," "radiotherapy" and "prostatectomy" from 1990 until April, 2014. Articles were also identified through searches of references of these articles. RESULTS: Retrospective series and population-based data suggest that the use of local treatment of the prostate in patients with primary metastatic prostate cancer may improve cancer-specific survival and overall survival compared with treating these patients with androgen deprivation therapy alone. The clinical outcome in metastatic prostate cancer is largely determined by the extent of lymph node involvement and overall metastatic burden. Contemporary data are lacking to recommend one alternative of local therapy (radiotherapy or radical prostatectomy) over the other. The primary limitation of this literature review is the lack of published randomized trial assessing the role of local treatment in addition to systemic therapy. CONCLUSIONS: Local treatment appears to improve oncologic outcomes in metastatic prostate cancer patients. Nevertheless, due to the lack of high-quality evidence, its role needs to be confirmed in future prospective trials. The selection of ideal candidates and optimal treatment alternative (radiotherapy, radical prostatectomy or other) warrants further investigation.

Prognostic effect of neuroendocrine differentiation in prostate cancer: A critical review.

BACKGROUND: The multiple pathways that are involved in neuroendocrine differentiation (NED) in prostate cancer (PCa) are poorly elucidated. Evidence suggests that several environmental triggers induce NED leading to the adaptation of PCa to its close environment to maintain cell proliferation. Nevertheless, there is conflicting evidence regarding the prognostic role of NED in PCa. METHODS: In this review, we aimed to summarize all available data about NED and to assess the prognostic role of NED in disease progression and therapy resistance, and its role in routine clinical practice. This review was based on articles found through a PubMed literature search between 1993 and 2013. The study outcome measure was the effect of NED on oncologic outcomes at each PCa stage. RESULTS: In total, 59 articles reporting on the effect of NED on oncologic outcomes have been selected. In clinical practice, immunostaining for NED markers could have interesting predictive value for assessing the oncologic outcomes in patients receiving androgen-deprivation therapy. Thus, patients with high NED burden may be candidates for more aggressive treatment strategies targeting NED pathways. Conversely, strong evidence is lacking concerning its potential independent prognostic value in hormone-naïve PCa. CONCLUSIONS: Current published data are not sufficient to recommend the use of NE markers in routine practice, particularly at early PCa stage.

What is the optimal definition of misclassification in patients with very low-risk prostate cancer eligible for active surveillance? Results from a multi-institutional series.

BACKGROUND: The risk of unfavorable prostate cancer in active surveillance (AS) candidates is nonnegligible. However, what represents an adverse pathologic outcome in this setting is unknown. We aimed at assessing the optimal definition of misclassification and its effect on recurrence in AS candidates treated with radical prostatectomy (RP). MATERIALS AND METHODS: Overall, 1,710 patients eligible for AS according to Prostate Cancer Research International: Active Surveillance criteria treated with RP between 2000 and 2013 at 3 centers were evaluated. Patients were stratified according to pathology results at RP: organ-confined disease and pathologic Gleason score ≤ 6 (group 1); organ-confined disease and Gleason score 3+4 (group 2); and non-organ-confined disease, Gleason score ≥ 4+3, and nodal invasion (group 3). Biochemical recurrence (BCR) was defined as 2 consecutive prostate-specific antigen (PSA) ≥ 0.2 ng/ml. Kaplan-Meier curves assessed time to BCR. Multivariable Cox regression analyses tested the association between pathologic features and BCR. Multivariable logistic regression analyses identified the predictors of adverse pathologic characteristics. RESULTS: Overall, 926 (54.2%), 653 (33.0%), and 220 (12.9%) patients were categorized in groups 1, 2, and 3, respectively. Median follow-up was 32.2 months. The 5-year BCR-free survival rate was 94.2%. Patients in group 3 had lower BCR-free survival rates compared with those in group 1 (79.1% vs. 97.0%, P<0.001). No differences were observed between patients included in group 1 vs. group 2 (97.0% vs. 94.7%, P = 0.1). These results were confirmed at multivariable analyses and after stratification according to margin status. Older age and PSA density ≥ 10 ng/ml/ml were associated with higher risk of unfavorable pathologic characteristics (i.e., inclusion in group 3; all P<0.001). CONCLUSIONS: Among patients eligible for AS treated with RP, only men with Gleason score ≥ 4+3 or non-organ-confined disease at final pathology were at increased risk of BCR. These individuals represent the real misclassified AS patients, who can be predicted based on older age and higher PSA density.

Clinical Perspectives from Randomized Phase 3 Trials on Prostate Cancer: An Analysis of the ClinicalTrials.gov Database.

BACKGROUND: It is not easy to overview pending phase 3 trials on prostate cancer (PCa), and awareness of these trials would benefit clinicians. OBJECTIVE: To identify all phase 3 trials on PCa registered in the ClinicalTrials.gov database with pending results. DESIGN AND SETTING: On September 29, 2014, a database was established from the records for 175 538 clinical trials registered on ClinicalTrials.gov. A search of this database for the substring "prostat" identified 2951 prostate trials. Phase 3 trials accounted for 441 studies, of which 333 concerned only PCa. We selected only ongoing or completed trials with pending results, that is, for which the primary endpoint had not been published in a peer-reviewed medical journal. RESULTS AND LIMITATIONS: We identified 123 phase 3 trials with pending results. Trials were conducted predominantly in North America (n=63; 51%) and Europe (n=47; 38%). The majority were on nonmetastatic disease (n=82; 67%), with 37 (30%) on metastatic disease and four trials (3%) including both. In terms of intervention, systemic treatment was most commonly tested (n=71; 58%), followed by local treatment 34 (28%), and both systemic and local treatment (n=11; 9%), with seven (6%) trials not classifiable. The 71 trials on systemic treatment included androgen deprivation therapy (n=34; 48%), chemotherapy (n=15; 21%), immunotherapy (n=9; 13%), other systemic drugs (n=9; 13%), radiopharmaceuticals (n=2; 3%), and combinations (n=2; 3%). Local treatments tested included radiation therapy (n=27; 79%), surgery (n=5; 15%), and both (n=2; 2%). A limitation is that not every clinical trial is registered on ClinicalTrials.gov. CONCLUSION: There are many PCa phase 3 trials with pending results, most of which address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively. PATIENT SUMMARY: This report describes all phase 3 trials on prostate cancer registered in the ClinicalTrials.gov database with pending results. Most of these trials address questions regarding systemic treatments for both nonmetastatic and metastatic disease. Radiation therapy and androgen deprivation therapy are the interventions most commonly tested for local and systemic treatment, respectively.