The day’s news update: Thursday, August 14

Today’s prostate cancer news update includes information related to the following areas:

  • Long-term survival of patients with PSA levels ≥ 50 ng/mL who have been treated with radical prostatectomy
  • The current role of bone imaging in the managment of prostate cancer
  • The potential of targeted therapy for androgen-independent prostate cancer, based on expression of specific molecular markers

Inman and colleagues at the Mayo Clinic have conducted a retrospective evaluation of the long-term outcomes of 236 men with prostate cancer and very high (≥50 ng/mL) preoperative serum PSA values who were treated with radical retropubic prostatectomy (RRP) between 1987 and 2004.  Such patients are increasingly rare in the US today, but are still relatively common in the developing world. The study cohort was divided into 2 groups: patients with PSA levels between 50 and 99 ng/mL (Group A) and patients with PSA levels ≥ 100 ng/mL (Group B). Biochemical recurrence was defined as a single postoperative serum PSA value ≥ 0.4 ng/mL. Systemic disease progression was defined as the development of a local recurrence or systemic metastases, and any death resulting from prostate cancer or its treatment was defined as a cancer-specific mortality. The authors report biochemical recurrence-free survival rates of 43 percent and 36 percent at 10 years for patients in Group A and B, respectively. Systemic progression-free survival rates in Groups A and B were 83 percent and 74 percent at 10 years, respectively. The estimated overall cancer-specific survival was 87 percent at 10 years. The authors conclude that patients with prostate cancer and a serum PSA level ≥ 50 ng/mL have prostate cancer with a very high likelihood of being pathologically advanced. Although the probability of realizing long-term survival in these high-risk patients is less than in patients with more favorable disease, 10-year survival outcomes are surprisingly high. (It should be noted that surgery was not the only therapy used in these patients over time. They may have received several other forms of adjuvant and follow-up treatment.)

Dotan has published a review of the current use of bone imaging technologies in the management of prostate cancer. He makes a number of key points in this review: Bone metastases can be suspected clinically and by laboratory tests, but a final diagnosis relies on radiographic evidence. Conventional bone scans are preferred to plain-film radiography for surveillance of the entire skeleton. Radiologic diagnosis of bone metastases, particularly in patients with low burden of disease, is difficult because non-cancerous bone lesions that mimic cancer are common. Conventional bone scans have low sensitivity and high false-negative rates (up to 40 percent) compared with advanced modalities such as PET, PET-CT and MRI, which can assist in diagnosis and may even replace conventional scanning methods in time. The correct diagnosis of bone involvement in prostate cancer is crucial to assessment of the effects of therapy on the primary tumor, the patient’s prognosis, and the efficacy of bone-specific treatments that can reduce future bone-associated morbidity. Dr Dotan also notes that predictive tools such as nomograms enable the identification of patients at risk of bone involvement during the course of their disease.

Ohlmann et al. have investigated the so-called “expression profile” of molecular markers that are candidates for targeted therapy in patients with progressive androgen-independent prostate cancer (AIPC). This was a two-part study. In the first part, they took tissues biopsied from patients’ prostates, lymph nodes, and soft tissue metastases. Each tumor tissue was analyzed for the expression of six signal transduction factors: epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor β (PDGFRβ), Her-2/neu, c-KIT, and vascular endothelial growth factor (VEGF). Knowing the expression profile, the authors were then able to assess the potential efficacy of combination therapy with an appropriate signal transduction inhibitor (STI) and docetaxel (Taxotere).  In the second part of the study, patients whose tissues tested positive for one or more markers were given the opportunity to be treated with the corresponding STI and docetaxel. Fifty-one patients were included in the protocol, of whom 43 (84.3 percent) presented with progressive AIPC after first-line chemotherapy. Forty-six of these 51 patients (90.2 percent) showed expression of one or more of the analyzed markers. Expression of EGFR was found in 61.2 percent, PDGFRβ in 57.1 percent, Her-2/neu in 16.3 percent, c-KIT in 25.0 percent, and VEGF in 74.5 percent. Because of cost-related issues, only 8/51 patients received the relevant combination therapy and were evaluated for response. Four of the eight patients (50 percent) showed a decline in PSA of ≥ 50 percent, and the median survival time was 13.5 months at a median follow-up of 23.6 (11-35) months. Expression of molecular targets was evident in about 90 percent of patients with AIPC. Based on the expression profile, an individual treatment strategy can theoretically be applied to each patient. This is a fascinating step towards personalized care for patients with late stage prostate cancer that clearly demonstrated the impact of cost on the ability of patinets to actually receive treatment. It would be interesting to see a larger study of this type carried out in which patients could be guaranteed relevant drugs through the provision of products by the appropriate drug manufacturers. [Note: The abstract of this article is available in English, but the actual article is published in German.]

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