Castration-resistant prostate cancer: AUA Guideline.

PURPOSE: This Guideline is intended to provide a rational basis for the management of patients with castration-resistant prostate cancer based on currently available published data. MATERIALS AND METHODS: A systematic review and meta-analysis of the published literature was conducted using controlled vocabulary supplemented with keywords relating to the relevant concepts of prostate cancer and castration resistance. The search strategy was developed and executed by reference librarians and methodologists to create an evidence report limited to English-language, published peer-reviewed literature. This review yielded 303 articles published from 1996 through 2013 that were used to form a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. RESULTS: Guideline statements were created to inform clinicians on the appropriate use of observation, androgen-deprivation and antiandrogen therapy, androgen synthesis inhibitors, immunotherapy, radionuclide therapy, systemic chemotherapy, palliative care and bone health. These were based on six index patients developed to represent the most common scenarios encountered in clinical practice. CONCLUSIONS: As a direct result of the significant increase in FDA-approved therapeutic agents for use in patients with metastatic CRPC, clinicians are challenged with a multitude of treatment options and potential sequencing of these agents that, consequently, make clinical decision-making more complex. Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient's treatment goals. In all cases, patients' preferences and personal goals should be considered when choosing management strategies.

Long-term follow-up of a prospective trial of trimodality therapy of weekly paclitaxel, radiation, and androgen deprivation in high-risk prostate cancer with or without prior prostatectomy.

PURPOSE: Weekly paclitaxel, concurrent radiation, and androgen deprivation (ADT) were evaluated in patients with high-risk prostate cancer (PC) with or without prior prostatectomy (RP). METHODS AND MATERIALS: Eligible post-RP patients included: pathological T3 disease, or rising prostate-specific antigen (PSA) ≥ 0.5 ng/mL post-RP. Eligible locally advanced PC (LAPC) patients included: 1) cT2b-4N0N+, M0; 2) Gleason score (GS) 8-10; 3) GS 7 + PSA 10-20 ng/mL; or 4) PSA 20-150 ng/mL. Treatment included ADT (4 or 24 months), weekly paclitaxel (40, 50, or 60 mg/m(2)/wk), and pelvic radiation therapy (total dose: RP = 64.8 Gy; LAPC = 70.2 Gy). RESULTS: Fifty-nine patients were enrolled (LAPC, n = 29; RP, n = 30; ADT 4 months, n = 29; 24 months, n = 30; whites n = 29, African Americans [AA], n = 28). Baseline characteristics (median [range]) were: age 67 (45-86 years), PSA 5.9 (0.1-92.1 ng/mL), GS 8 (6-9). At escalating doses of paclitaxel, 99%, 98%, and 95% of doses were given with radiation and ADT, respectively, with dose modifications required primarily in RP patients. No acute Grade 4 toxicities occurred. Grade 3 toxicities were diarrhea 15%, urinary urgency/incontinence 10%, tenesmus 5%, and leukopenia 3%. Median follow-up was 75.3 months (95% CI: 66.8-82.3). Biochemical progression occurred in 24 (41%) patients and clinical progression in 11 (19%) patients. The 5- and 7-year OS rates were 83% and 67%. There were no differences in OS between RP and LAPC, 4- and 24-month ADT, white and AA patient categories. CONCLUSIONS: In addition to LAPC, to our knowledge, this is the first study to evaluate concurrent chemoradiation with ADT in high-risk RP patients. With a median follow-up of 75.3 months, this trial also represents the longest follow-up of patients treated with taxane-based chemotherapy with EBRT in high-risk prostate cancer. Concurrent ADT, radiation, and weekly paclitaxel at 40 mg/m(2)/week in RP patients and 60 mg/m(2)/week in LAPC patients is feasible and well-tolerated.

Hot flashes in prostate cancer: state of the science.

The lack of progress concerning the concept of the hot flash experience in men is an indication of the need for exploration of this phenomenon. The hot flash experience in men is a problem that can no longer be ignored. The results of this literature review will provide a foundation for additional development of the concept and facilitate further inquiry into the phenomenon. The purpose of the article is to provide the current state of the science of hot flashes related to androgen ablation treatment in prostate cancer patients; sleep, sweating, cognitive impairment, and the implications on health-related quality of life. Due to the sparse literature on this concept in men, information is extrapolated from the literature on female breast cancer patients treated with hormones and on menopausal women.

Physiology and endocrinology of hot flashes in prostate cancer.

The purpose of this article is to integrate the physiology of the male reproductive system and the role of hormones in the pathophysiology and treatment of prostate cancer. The primary focus is to review hormonal changes associated with androgen ablation treatment and to integrate the available hormonal data into a hypothesis. This review used a systematic search of Medline references from 1990 to 2006. All sources were critically evaluated to arrive at an understanding of androgen deprivation symptoms, such as hot flushes/flashes, and to identify research needed in this area. Research is needed to explore the physiological mechanisms of hot flashes to develop better therapeutic treatment options to ameliorate side effects of hormonal treatment. Studies are needed to investigate all aspects of hot flashes in populations other than those with breast cancer, such as men with prostate cancer, carcinoid tumors, medullary thyroid tumors, pancreatic islet-cell tumors, renal cell carcinoma, and phenochromocytoma.

Hot flashes.

CASE STUDY: Mr. J is a 68-year-old African American man with a history of advanced prostate cancer. He was diagnosed nine months prior with adenocarcinoma of the prostate, with a Gleason score of 9 and tumor, node, metastasis staging of T3 NO M1. His prostate-specific antigen (PSA) was 483 ng/ml at the time of diagnosis. He immediately began treatment with total androgen blockade after the staging workup was completed.

Hot flash experience in men with prostate cancer: a concept analysis.

PURPOSE/OBJECTIVES: To provide a clear definition of the hot flash experience in men with prostate cancer receiving hormonal treatment. DATA SOURCES: Articles, book chapters, and electronic sources. DATA SYNTHESIS: The hot flash experience has not been explored previously in men with prostate cancer. The physiologic and psychological scopes of the phenomenon are described as a multidimensional experience. CONCLUSIONS: The essential attributes of hot flashes in men consist of physiologic (e.g., warmth, sweating, chills) and psychological (e.g., anxiety, impaired memory, agitation) factors. Antecedents to the experience include demographics, disease, and treatment modality. Consequences include effects on sleep, cognition, and health-related quality of life. IMPLICATIONS FOR NURSING: Evaluation of the hot flash experience in men receiving hormonal ablation should include assessment of the symptoms associated with the treatment modality and nursing interventions to help ameliorate symptoms. Future research is needed to focus on providing symptom management to decrease the severity or prevent the occurrence of multiple symptoms related to androgen ablation therapy.

Docetaxel followed by hormone therapy in men experiencing increasing prostate-specific antigen after primary local treatments for prostate cancer.

PURPOSE: Prostatectomy or radiation for localized prostate cancer (PC) can fail in up to 15% to 30% of patients. The purpose of this study was to determine feasibility, tolerability, and outcome of docetaxel followed by hormone therapy in men experiencing an increasing prostate-specific antigen (PSA) after their primary local treatments for PC. PATIENTS AND METHODS: Men with increasing serum PSA after prostatectomy or/and radiation were eligible. Serum PSA had to be > or = 4 ng/mL and serum testosterone had to be in the noncastrate range. Treatment included docetaxel 70 mg/m2 every 3 weeks for up to six cycles, followed by total androgen suppression (luteinizing hormone-releasing hormone agonist plus bicalutamide) and peripheral androgen blockade (finasteride plus bicalutamide) for 12 to 20 months. RESULTS: Thirty-nine men were enrolled; 32 had PSA-only failure, seven also had clinical metastasis. Baseline median PSA was 13.7 ng/mL. Serum PSA decreased > or = 50% in 17 of 35 patients (48.5%) and > or = 75% in seven of 35 patients (20%) with docetaxel. The PSA decreased to a median of 0.1 ng/mL with subsequent hormone therapy. In 28 of 33 patients the PSA increased (median, 0.41 ng/mL) at a median follow-up of 2.3 months after treatment. In contrast, in five of 33 men the PSA remains at 0.1 ng/mL at a median of 18.9 months after therapy; three of these five men had soft tissue metastasis at entry but remain in complete remission. The most common grade 3 to 4 toxicity was neutropenia (61.5%). CONCLUSION: Docetaxel followed by hormone therapy of limited duration may provide disease control in subgroups of men experiencing failure after local treatments for PC.