Luteinizing hormone-releasing hormone antagonists in prostate cancer.

Luteinizing hormone-releasing hormone (LHRH) antagonists work by directly inhibiting LHRH without any initial stimulation of the LHRH receptor. The physiologic response is a direct and rapid decrease in luteinizing hormone, follicle-stimulating hormone, and testosterone without any flare. Although there has been extensive basic-science work on these medications, practical shortcomings have limited clinical studies in prostate cancer. Many of these compounds induce significant histamine-mediated side effects, and until recently, no depot form existed. In 2 recent phase-3 studies comparing abarelix depot with leuprolide and with leuprolide plus bicalutamide, abarelix lowered serum testosterone more quickly. None of the 89 patients on leuprolide alone were castrate on day 8 as opposed to 72% of the 180 patients randomized to abarelix (P <0.001). Similarly, none of the combination group were castrate by day 8, whereas 68% of the abarelix patients were castrate (P <0.001). In addition, 82% of the patients treated with leuprolide and 86% of those given leuprolide/bicalutamide had testosterone surge, whereas none of the abarelix patients did (P <0.001 for both studies). Both phase 2 and phase 3 data show abarelix to be well tolerated. In conclusion, LHRH antagonists offer the physiologic response of orchiectomy without surgery. These medications are well tolerated and a depot form now exists. The expansion of indications for androgen deprivation, such as downsizing or intermittent therapy, could provide many opportunities for their use. Despite these encouraging advances, however, their routine use for advanced prostate cancer may depend on demonstration of a survival advantage in avoiding flare.

The clinical utility of serologic markers in the evaluation of the acute scrotum.

OBJECTIVE: To examine the presence of interleukin-1 (IL-1), interleukin-6 (IL-6), and creatine phosphokinase-MM (CPK-MM) in patients with acute scrotal pain and assess their clinical utility in the diagnosis of testicular torsion (TT) and epididymitis. METHODS: Twenty-five patients with acute scrotal pain were prospectively enrolled over a two-year period. History, physical examination, complete blood count, urinalysis, and scrotal ultrasound were performed. Testicular torsion was confirmed by surgical exploration. Epididymitis was diagnosed using physical examination, scrotal ultrasound, and positive urinalysis. Venous blood was assayed for IL-1, IL-6, and CPK-MM in triplicate during the routine drawing of blood in the emergency department. The data are reported as medians +/- interquartile ranges (IQRs). RESULTS: Twenty-five patients with acute scrotal pain were evaluated; 11 with TT, three with torsion of the appendix testis (TAT), ten with epididymitis, and one with varicocele. One patient had both TT and epididymitis. Interleukin-1 was not detectable in either group. The CPK-MM values between TT and epididymitis were virtually identical at 99.8 and 100 IU/L, respectively. The median value for IL-6 was 1. 03 (IQR = 0.19 to 2.86) vs 20.86 (IQR = 2.14 to 65.50) pg/mL in the torsion and epididymitis groups, respectively. The 97.5% CI for the difference of medians of 19.9 was 0.4 to 65.1, p = 0.02. Using receiver operating characteristic (ROC) curve analysis for IL-6, the area under the curve was 0.82 for torsion and 0.67 for epididymitis. Using a cutoff value of IL-6 >/= 1.41 pg/mL, the positive predictive value of IL-6 in diagnosing epididymitis was 78.6%, with a negative predictive value of 100% for TT. There were no cases of missed TT on follow-up. CONCLUSIONS: This preliminary investigation of serologic markers demonstrates that IL-6 is significantly elevated in epididymitis as compared with TT. Creatine phosphokinase-MM and IL-1 were not found to be of diagnostic utility. The small sample size of this study precludes a definitive conclusion as to the utility of these markers in the emergency department. However, IL-6 may be clinically useful as an additional element in differentiating the causes of acute scrotal pain, and further study is warranted.

Prognostic significance of the 1997 TNM classification of renal cell carcinoma.

PURPOSE: The TNM classification of renal cell carcinoma was recently revised in 1997. The most significant change from the previous edition (1987) is an increase in the size cutoff between T1 and T2 tumors from 2.5 to 7.0 cm. We compared the 1997 and 1987 TNM staging classifications in predicting patient outcome. MATERIALS AND METHODS: A total of 381 patients who underwent nephrectomy for renal cell carcinoma at our hospital between 1968 and 1994 were identified. Mean patient age was 61 years (range 15 to 89) and mean followup was 64.5 months. All pathological slides were re-reviewed in uniform manner and staged using the 1987 and 1997 TNM classifications. The impact of numerous pathological factors and each staging classification on disease specific survival and freedom from progression were statistically analyzed, and Kaplan-Meier survival curves were generated and compared. RESULTS: The 1997 TNM classification resulted in a redistribution of 170 cases previously classified as stage II (T2N0M0) to stage I (T1N0M0) under the new system. Both classifications were strong predictors of survival on univariate and multivariate analyses, and essentially equivalent in the ability to predict patient outcome. However, comparison of survival curves on Kaplan-Meier life tables revealed better separation of survival for stage I (T1N0M0) and stage II (T2N0M0) cases under the 1997 TNM classification, with survival for TNM stage I essentially remaining unchanged. CONCLUSIONS: The 1997 TNM classification of renal cell carcinoma appears to be equivalent to the previous classification in predicting outcome but permits better stratification of cases according to survival and, therefore, may have improved clinical usefulness.

Cost comparison of orchiectomy and leuprolide in metastatic prostate cancer.

PURPOSE: We objectively compare the costs associated with the medical and surgical treatment of metastatic prostate cancer. MATERIALS AND METHODS: We analyzed and compared itemized billing statements for 28 men with metastatic adenocarcinoma of the prostate. Half of the men were treated medically with the luteinizing hormone-releasing hormone analogue leuprolide, while the other half underwent bilateral therapeutic orchiectomy. In addition, differences in hospital cost to treat these men were calculated. RESULTS: During a mean followup of 24 months leuprolide treated patients were charged $500.00 per month of treatment compared to average monthly expenditure of $226.00 for orchiectomy patients during a 23-month interval. By 9 months charges incurred by both groups were equal and by 20 months medically treated patients accumulated urological charges twice that of the surgically treated patients. The true hospital cost to treat these patients followed the same trend, that is the medically treated group cost twice as much to treat by 15 months. For the average stage D2 case leuprolide therapy charges were $9,420, or 63%, more than orchiectomy. Similarly, leuprolide cost the hospital $8,924 more than surgery. CONCLUSIONS: Medical management of metastatic prostate cancer is expensive. With broadening applications and androgen deprivation being initiated earlier in the course of disease, the amount spent on medical therapy will continue to escalate. For patients with a life expectancy of more than 9 months orchiectomy is the most cost-effective treatment option.

Determining prognosis of clinically localized prostate cancer by immunohistochemical detection of mutant p53.

OBJECTIVES: Mutations of the p53 tumor suppressor gene can result in unregulated cellular growth and have been implicated in numerous malignancies. The objective of this study was to determine whether the detection of mutant p53 by immunohistochemical staining is predictive of progression in clinically localized adenocarcinoma of the prostate. METHODS: Immunohistochemical staining for mutant p53 was performed on 40 formalin-fixed radical prostatectomy specimens. Benign glands in the sections served as controls. Immunoreactivity (IR) was categorized semi-quantitatively from 0 to 4+ (0 = no IR, 1+ = 1 % to 10%, 2+ = 11% to 40%, 3+ = 41 % to 70%, 4+ = 71 % to 100%). Results were then compared to Gleason score, Stage (T2 versus T3), surgical margins, lymph node and seminal vesicle involvement, age, race, preoperative prostate-specific antigen (PSA), and biochemical progression. Biochemical progression was defined as a persistently elevated postoperative PSA of 0.2 ng/mL or greater. RESULTS: Thirty-two of the 40 tumors (80%) stained for mutant p53. None of the tumors that did not stain progressed, whereas 20 of 32 (62.5%) of the tumors that did stain progressed, with an overall mean followup of 50.8 months. Immunoreactivity did not correlate with any of the known prognostic variables but did have statistically significant correlation with progression by all three statistical methods used (Fisher's exact test, logistic regression, and log-rank test). CONCLUSIONS: Strict quality control and newer antigen retrieval techniques reveal p53 abnormalities in many prostate cancers. Immunohistochemical detection of mutant p53 appears to be an independent predictor of progression. These data suggest potential utility of p53 as a preoperative prognostic indicator in localized prostate cancer.

Congenital prostatic cyst causing ejaculatory duct obstruction: management by transrectal cyst aspiration.

Congenital prostatic cysts are relatively uncommon and rarely symptomatic. We describe a 24-year-old man who presented with a 2-month history of anejaculation accompanied with bilateral epididymal pain. Transrectal ultrasonography of the prostate revealed a large midline prostatic cyst and bilateral dilatation of the seminal vesicles. Transrectal aspiration of the cyst resulted in return of antegrade ejaculation and resolution of epididymal pain.

Detection of non-palpable prostate cancer. A mathematical and laboratory model.

Prostate cancer is currently the most commonly diagnosed cancer among males in the United States. As technology improves and the search for this enigmatic condition intensifies, we are detecting greater numbers of non-palpable tumours. These tumours are generally treated aggressively, given the uncertainty of their behaviour, but this approach may be over-zealous for small volume disease. The likelihood of detecting any cancer volume can be derived from Bayes' theorem of conditional probability. A laboratory model using coloured clay was created to contrast tumour volumes of 2.5, 5 and 20% (n = 75). Six random systematic biopsies were taken from each model in a blind fashion; 36% of the 2.5%, 44% of the 5% and all of the 20% models had at least 1 positive biopsy. Twenty-two of the 25 models representing 20% tumour had 3 or more biopsy cores positive. These data suggest that low volume disease with low biological potential will be found by random biopsy as the mathematical probability predicts. The high incidence of occult prostate cancer in the older population makes this a worrying observation. Also, and perhaps more important, there is a direct correlation between the volume of disease and the number of positive biopsies. This correlation is easily seen in both models and may allow for an estimation of tumour volume. This ability to estimate tumour volume may be a useful clinical tool that helps to guide therapy and assess prognosis.