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PURPOSE: Current androgen deprivation therapies for men with prostate cancer cause accelerated osteoporosis and a significant risk of osteoporotic fracture. We have recently shown that transdermal estradiol is an effective alternative for such patients. Here we report the impact of transdermal estradiol therapy on the bone mineral density of men with prostate cancer. MATERIALS AND METHODS: A total of 20 patients with newly diagnosed locally advanced or metastatic prostate cancer were treated with transdermal estradiol patches. Bone mineral density of the lumbar spine and the proximal femur was measured with dual-energy x-ray absorptiometry, and correlated with computerized tomography and isotope bone scan findings at 6-month intervals. RESULTS: In all measured regions bone mineral density increased with time. By 1 year mean bone mineral density +/- SEM had increased by 3.60% +/- 1.6% in the lumbar spine (p = 0.055), 2.19% +/- 1.03% in the femoral neck (p = 0.055), 3.76% +/- 1.35% in the Ward's region (p = 0.008) and 1.90% +/- 0.85% in the total hip (p = 0.031), respectively. Of 12 osteoporotic sites 4 had improvement based on World Health Organization grading. All other sites improved toward a better classification. CONCLUSIONS: Transdermal estradiol protects against bone loss in men with prostate cancer and may improve bone density in those at risk for osteoporotic fracture.

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OBJECTIVE: To evaluate whether serum squamous cell carcinoma antigen (SCCAg) measurements may be of use in identifying nodal metastases in patients with SCC of the penis after treating the primary tumour. PATIENTS AND METHODS: The levels of SCCAg were analysed in 11 men with penile SCC between 1994 and 2001. RESULTS: An elevated SCCAg level had a sensitivity of 57% (95% confidence interval, CI, 18-90%) and a specificity of 100% (CI 40-100%) for nodal metastases. Levels of SCCAg increased exponentially in patients who developed nodal metastases after treatment of the primary tumour, and were elevated before clinical or radiological evidence of nodal disease. CONCLUSION: Either the absolute level or the rate of rise of SCCAg may be a useful tool with which to follow patients after excision of the primary tumour. It may be more sensitive than computed tomography and magnetic resonance imaging in detecting recurrence, but further evaluation is needed.

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PURPOSE: Current hormonal therapies for prostate cancer are associated with significant morbidities, including symptoms of andropause and osteoporosis. Oral estrogens prevented many of these problems but were abandoned due to cardiovascular toxicity attributed to hepatic effect. In contrast, parenteral estrogens prevent first pass hepatic metabolism and substantially reduce cardiovascular risk, and long-term transdermal estradiol therapy is believed to be cardioprotective. We report preliminary results of a pilot study using transdermal estradiol therapy to treat men with advanced prostate cancer. MATERIALS AND METHODS: A total of 20 patients with advanced prostate cancer were enrolled in a before and after study that examined the impact of estradiol patches on hormones, disease, thrombophilia, vascular flow, osteoporosis and quality of life. RESULTS: Median followup is 15 months. Estradiol levels greater than 1,000 pmol./l. were achieved using 2 patches and higher levels were obtained by increasing the number of patches. All patients achieved castrate levels of testosterone within 3 weeks and had biochemical evidence of disease regression. One patient died of disease at 14 months and 1 cardiovascular complication occurred. Thrombophilic activation was avoided and vascular flow improved. Bone mineral density was significantly increased. Mild or moderate gynecomastia occurred in 80% of patients but no patient had hot flushes. All other functional and symptomatic quality of life domains improved. CONCLUSIONS: Transdermal estradiol therapy produced an effective tumor response. Cardiovascular toxicity was substantially reduced compared with that expected of oral estrogen, and other morbidity (gynecomastia) was negligible. Transdermal estradiol therapy prevented andropause symptoms, improved quality of life scores and increased bone density. Transdermal estradiol costs a tenth of current therapy cost, with the potential for considerable economic savings over conventional hormone therapies.

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The collection of prostate biopsies into individual or site-specific specimen containers has not been performed routinely because of concerns of time, cost and lack of additional clinical value. This report evaluates the first ever use of a multicompartment microcassette for the collection and processing of site-specific prostate biopsies.Site-specific prostate biopsies were taken in sequential men suspected to have prostate cancer and collected in a multicompartment microcassette, which holds six biopsies and fits within a standard specimen container. Estimates were made of the cost and time savings compared with biopsies collected in individual specimen containers. In 88 men evaluated, use of the multicompartment microcassette saved time (72% reduction) and cost (83% reduction) with the added ability of easy identification of the site of each prostate biopsy. The multicompartment microcassette is a convenient, time- and cost-effective container for the collection of site-specific prostate biopsies.

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PURPOSE: We explored the relationships of office assessment of lower urinary tract symptoms, transrectal ultrasound measurement and the bladder outlet obstruction index, as derived from pressure flow studies. We also developed and validated a multivariate analysis for predicting the bladder outlet obstruction index. MATERIALS AND METHODS: We evaluated 384 men with lower urinary tract symptoms using the International Prostate Symptom Score, maximum urine flow, post-void residual urine, transrectal ultrasound and urodynamic studies. Data were analyzed by multiple linear regression with continuous variables. A simple algorithm, that is the predicted bladder outlet obstruction index, was created using the best fit variables identified from a derivation set and assessed in a separate validation set. The predicted index was applied to predict the probability of actual obstruction according to office parameters. RESULTS: Maximum urine flow and total prostate volume predicted the bladder outlet obstruction index most completely (adjusted R2 = 0.50, F 75.9, p <0.0001), while other variables were not helpful. These variables were used to create the predicted bladder outlet obstruction index algorithm, antilog10 (2.21 - 0.50 log maximum urine flow + 0.18 log total prostate volume) - 50. In the 42% of patients with a predicted index of greater than 40 there was a 92% risk or positive predictive value of equivocal or worse obstruction, whereas a predicted index of less than 20 in 23% indicated a 4% risk of significant obstruction. CONCLUSIONS: The bladder outlet obstruction index can be predicted from maximum urine flow and prostate volume. Development of the predicted bladder outlet obstruction index algorithm enables the mathematical prediction of obstruction from these simple measures. Using the predicted bladder outlet obstruction index clinicians can determine the risk of obstruction in individuals. In 65% of patients we predicted equivocal or worse obstruction with greater than 90% confidence.

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BACKGROUND: Although ion channels are known to contribute to a variety of basic cellular behaviors involved in the metastatic cascade, their role in metastasis per se has only recently been questioned. The hypothesis tested was whether K(+) channels were different between strongly metastatic PC-3 and weakly metastatic LNCaP human prostate cancer cell lines. METHODS: The whole-cell configuration of the patch clamp recording technique was used to record voltage-gated currents from LNCaP and PC-3 cell lines. The responses to different voltage-clamp protocols, sensitivity to external Ca(2+), and addition of drugs and toxins were explored. RESULTS: Voltage-gated K(+) current density was significantly larger in LNCaP than PC-3 cells. In addition, the K(+) currents in a sub-population of PC-3 cells were Ca(2+)-sensitive. These properties reflected the differential metastatic character of the cells, the PC-3 cells appearing potentially more "excitable". CONCLUSIONS: Prostate cancer cells of varying metastatic ability can be distinguished by their ion channel characteristics. The possible contribution(s) of K(+) channel activity to development of malignancy needs exploration.

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OBJECTIVES: To compare the accuracy achieved by a trained urology nurse practitioner (UNP) and consultant urologist in detecting bladder tumours during flexible cystoscopy. PATIENTS AND METHODS: Eighty-three patients underwent flexible cystoscopy by both the UNP and consultant urologist, each unaware of the other's findings. Before comparing the findings, each declared whether there was tumour or any suspicious lesion requiring biopsy. RESULTS: Of 83 patients examined by flexible cystoscopy, 26 were found to have a tumour or a suspicious lesion. One tumour was missed by the UNP and one by the urologist; each tumour was minute. Analysis using the chance-corrected proportional agreement (Kappa) was 0.94, indicating very close agreement. CONCLUSION: A UNP can be trained to perform cystoscopy and detect suspicious lesions as accurately as can a consultant urologist. Legal and training issues in implementation are important.

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Prostate cancer is an enigmatic disease. Although prostatic-intraepithelial neoplasia appears as early as the third decade and as many as 80% of 80 year old men have epithelial cells in their prostate that fit the morphological criteria for cancer, only about 10% of men will ever have the clinical disease and less than 3% will die from it. There have been no significant proven interventions which have altered the natural history of the disease since hormone down regulation was introduced in the 1940s and new research has been poorly supported. There is however an urgent need to develop new criteria to distinguish those patients with localised disease who will benefit from intervention from those that do not require it or who will have occult extra prostatic metastases. Similarly, there is an urgent need to develop new treatments for those in whom the disease is extra-prostatic and therefore incurable by conventional treatments. This review covers the latest developments in epidemiology, cellular and molecular biology including new areas such as ion channels in the field of prostate cancer.

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Ion channels are important for many cellular functions and disease states including cystic fibrosis and multidrug resistance. Previous work in the Dunning rat model of prostate cancer has suggested a relationship between voltage-activated Na+ channels (VASCs) and the invasive phenotype in vitro. The objectives of this study were to 1) evaluate the expression of VASCs in the LNCaP and PC-3 human prostate cancer cell lines by Western blotting, flow cytometry, and whole-cell patch clamping, 2) determine their role in invasion in vitro using modified Boyden chambers with and without a specific blocker of VASCs (tetrodotoxin). A 260-kd protein representing VASCs was found only in the PC-3 cell line, and these were shown to be membrane expressed on flow cytometry. Patch clamping studies indicated that functional VASCs were present in 10% of PC-3 cells and blocking these by tetrodotoxin (600 nmol/L) reduced their invasiveness by 31% (P = 0.02) without affecting the invasiveness of the LNCaP cells. These results indicate that the reduction of invasion is a direct result of VASC blockade and not a nonspecific action of the drug. This is the first report of VASCs in a human prostatic cell line. VASCs are present in PC-3 but not LNCaP cells as determined by both protein and functional studies. Tetrodotoxin reduced the invasiveness of PC-3 but not LNCaP cells, and these data suggest that ion channels may play an important functional role in tumor invasion.

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The voltage-gated ionic currents of two rodent prostatic cancer cell lines were investigated using the whole-cell patch clamp technique. The highly metastatic Mat-Ly-Lu cells expressed a transient, inward Na+ current (blocked by 600 nM tetrodotoxin), which was not found in any of the weakly metastatic AT-2 cells. Although both cell lines expressed a sustained, outward K+ current, this occurred at a significantly higher density in the AT-2 than in the Mat-Ly-Lu cells. Incubation of the Mat-Ly-Lu cell line with 600 nM tetrodotoxin significantly reduced the invasive capacity of the cells in vitro. Under identical conditions, tetrodotoxin had no effect on the invasiveness of the AT-2 cells.

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