Clinical prostate cancer最新文献

Purpose

First-line chemotherapy with docetaxel in patients with progressive castrate metastatic prostate cancer has been shown to improve overall survival compared with mitoxantrone-based therapies. The use and outcomes of chemotherapy after first-line antimicrotubule-based therapy have not been well described.

Patients and Methods

Patients with progressive castrate metastatic prostate cancer enrolled on an antimicrotubule-based protocol for treatment were followed to determine their baseline characteristics and outcomes with second- or third-line systemic therapy.

Results

Of 108 patients treated with antimicrotubulebased therapy, 81% received second-line therapy, and 40% received third-line therapies. Corresponding prostate-specific antigen (PSA) decreases ≥ 50% were observed in 72%, 15%, and 22% of patients. Median survival times from the start of first-, second-, and third-line therapy were 21 months (95% confidence interval [CI], 18-25 months), 13 months (95% CI, 10-15 months) and 12 months (95% CI, 9-19 months). Significant prognostic indicators for survival in the second-line setting include pretreatment PSA level, alkaline phosphatase level, and performance status. Patients not fit to receive second-line therapy were more symptomatic with first-line therapy, as illustrated by a greater need for narcotic therapy (67% vs. 15%) and palliative radiation therapy after first-line therapy (57% vs. 10%) in lieu of second-line systemic therapy.

Conclusion

Eighty percent of patients received second-line chemotherapy, with a median survival of 12 months from the start of second-line treatment. Although only 40% received third-line chemotherapy, median survival was similar to that of patients in the second-line setting. Our data show that patients who initiate chemotherapy with symptoms are more likely to require palliative radiation therapy rather than chemotherapy as second-line therapy. A sequential or continuous administration of therapy may optimize the care of this subset of symptomatic patients.

Prostate-specific membrane antigen (PSMA) is a relatively omnipresent molecule with a multiplicity of functions and has been shown to be a reasonable target for immunologic approaches such as vaccines or more directed therapy with radioactively labeled monoclonal antibodies against PSMA. Given the abundance of various glycoprotein and carbohydrate antigens expressed on the surface of prostate cancer cells and cell lines, PSMA stands out as another self-antigen that is not only expressed on cancer cells but also on neovasculature. Although vaccines are varied in their design and target goal, recent technology has afforded researchers the opportunity to induce recruitment of multiple effector cell populations, cytokines, and factors that can elicit cellular and humoral responses. This review serves to present unique approaches in vaccine development that can induce immunologic responsiveness to PSMA with potential impact on disease progression.

We report a case of orbital metastasis from a neuroendocrine dedifferentiated prostate cancer during progression from hormone-sensitive to hormone refractory stage. A patient receiving androgen deprivation for hormone-sensitive prostate cancer presented with sudden-onset rightsided ptosis and an increasing serum prostate-specific antigen level. Imaging studies revealed a mixed blastic and lytic lesion involving the right orbital wall and the right cavernous sinus. Comparison of the metastatic histology with the original pathology confirmed a histologic change to poorly differentiated prostate adenocarcinoma with neuroendocrine features. Local radiation of the lesion and palliative systemic chemotherapy resulted in marked short-term improvement of all presenting symptoms. Because prostate cancer metastasis involves hematogenous and lymphatic routes, we also evaluated expression of the vascular endothelial growth factor (VEGF) and receptors (VEGFR-1, VEGFR-2, and VEGFR-3) in the metastatic deposit by immunohistochemistry. Strong expression of VEGFR-2 and VEGFR-3 restricted to the malignant epithelium was noted. We recommend a second biopsy of atypical prostate metastasis associated with sudden change to aggressive clinical behavior in order to evaluate for dedifferentiation features before planning appropriate treatment interventions especially in patients who are candidates for systemic chemotherapy.

Purpose

Microvessel density within the prostate is associated with presence of cancer, disease stage, and disease-specific survival. We evaluated multidetector computed tomography (CT) to estimate prostate perfusion and localize prostate cancer.

Patients and Methods

Ten subjects were evaluated with contrast enhanced CT before radical prostatectomy with the Mx8000IDT 16-slice scanner. Following baseline pelvic scan, 100 cc of Optiray® 300 was administered intravenously (4 cc per second). Repeated dynamic scans through the prostate were obtained at 20, 30, 40, 50, and 60 seconds following initiation of contrast injection. Computed tomography perfusion was compared with pathologic findings of Gleason score and tumor volume on whole-mount prostatectomy specimens.

Results

Conventional adenocarcinoma (Gleason score, 6-10) was present in all subjects, including one who also demonstrated a mucinous variant of prostate cancer. Visible focal CT enhancement was noted in 1 patient with a high-volume tumor and a Gleason score of 10. A positive correlation between local estimates of CT perfusion and percent of prostate volume occupied by tumor in each sextant was found for half of the subjects (Pearson correlation coefficient, 0.3-0.95; mean, 0.48) but statistically significant correlation (P < 0.05; Pearson coefficient, 0.9- 0.95) was present in only the 2 subjects with the highest Gleason scores (8 and 10) and the highest tumor volume (≥ 50% in ≥ 1 sextant region).

Conclusion

Visible enhancement of prostate cancer during dynamic CT is present in a minority of subjects. Correlation between quantitative CT perfusion and tumor location is statistically significant only in subjects with localized high-volume, poorly differentiated prostate cancer.

Background

Hormone-refractory prostate cancer (HRPC) has modest response rates to second-line estrogenic agents such as diethylstilbestrol and the herbal product PC SPES. Estramustine phosphate (EMP) is a microtubule inhibitory agent with estrogenic properties commonly used in patients with metastatic HRPC. To determine whether previous response to second-line estrogen therapy would predict subsequent response to EMP-based chemotherapy, a retrospective study was conducted.

Patients and Methods

Patients with HRPC previously treated with second-line estrogenic therapy who subsequently received EMPbased chemotherapy were enrolled in a retrospective analysis. The progression of disease or response to treatment was determined with use of standard prostate-specific antigen (PSA) criteria and Response Evaluation Criteria in Solid Tumors.

Results

Seventy-eight patients were included in the analysis. Twenty-five patients with disease progression after receiving estrogen therapy received subsequent EMP-based chemotherapy. Overall, initial PSA response to any estrogen therapy was 54%. The overall PSA response to EMP-based chemotherapy was 60%, and the objective response was 36%. The PSA response to subsequent EMP-based chemotherapy was independent of patients having a previous response to estrogen therapy (70% vs. 53%; P = 0.68). The median overall survival for patients receiving estrogenic therapy and subsequent EMPbased chemotherapy was 12.7 months.

Conclusion

Previous response to second-line hormonal maneuvers with estrogen therapy does not predict subsequent response to EMP-based chemotherapy.