Decreased prostate cancer-specific survival of men with BRCA2 mutations from multiple breast cancer families.

The role of a germ-line BRCA2 mutation in the development of prostate cancer is established, but the clinical presentation linked to outcome for this group of men has not been well described. A total of 148 men from 1,423 families were ascertained from the kConFab consortium. Each participant met the following criteria: (i) a verified case of prostate cancer; (ii) confirmed as either a carrier or noncarrier of a family-specific BRCA pathogenic mutation; (iii) comprehensive clinical and treatment data were available. Clinical data were linked to treatment received and overall survival was analyzed by Kaplan-Meier. Prostate cancer in men from breast cancer-prone families has a high risk of disease progression, irrespective of mutation status. BRCA2 mutation carriers have an increased risk of death and prostate cancer-related death [HR (95% CI) 4.5 (2.12-9.52), P = 8.9 × 10(-5)] by comparison with noncarriers. Serum PSA readings taken prior to diagnosis in 90% of all men, age adjusted, were above clinical significance. Following D'Amico risk stratification, 77.5% of BRCA2 mutation carriers and 58.7% of noncarriers had high-risk disease. BRCA2 mutation status was also an independent prognostic indicator of overall survival. Furthermore, there was a poor overall survival outcome for both the BRCA2 mutation carriers and noncarriers given curative-intent treatment. All men in breast cancer-prone families are at risk of developing aggressive prostate cancer. This information is significant and should be included in discussions with genetic counselors and medical professionals when discussing prostate cancer treatment options for men in these families, irrespective of mutation status.

Stabilization of renal deterioration caused by bladder volume dependent obstruction.

PURPOSE: Previously published data from our unit show the detrimental effect of excessive bladder filling at normal pressure on renal function in chronically dilated renal units. Synchronous cystometry and dynamic renography identified a critical volume of filling that prevents upper tract drainage. In this followup study we determined whether maintaining bladder volume below this critical level would halt renal deterioration. MATERIALS AND METHODS: Followup data were collected on 20 patients in the original study. All had progressive renal function deterioration for which no other cause was identified. Creatinine measured nearest to the time of the study renogram served as a baseline and subsequent values were used to monitor renal function. Data were analyzed by the paired Student t test. RESULTS: Complete data were obtained on 14 patients with a mean age of 34.4 years (range 22 to 70). The mean glomerular filtration rate at entry to this part of the study was 42 ml per minute per 1.73 m(2) (range 18 to 69). Four patients had a neuropathic bladder, 4 had posterior urethral valves, 4 had bladder exstrophy, 1 had radiation cystitis, 1 had a solitary pelvic kidney and detrusor failure, 5 had a native bladder and 9 underwent cystoplasty. Drainage was via the native urethra and a Mitrofanoff channel in 7 cases each. Mean followup was 27 months (range 3 to 39). There was no significant difference in mean +/- SD creatinine at baseline vs latest followup (168 +/- 72 vs 185 +/- 90 micromol/l, p >0.05). CONCLUSIONS: In patients with bladder volume dependent renal obstruction function can be stabilized by consistently maintaining bladder volume below the critical level.

Effect of the abnormal bladder when full on upper tract drainage using a combined cystometrogram-(99m)Tc-mercapto-acetyltriglycine renogram: a prospective study.

OBJECTIVE: To examine the relevance of bladder volume in patients with chronic hydronephrosis and abnormal bladder function who lose renal function even though the bladder or reservoir pressure is normal (<40 cmH(2)0). PATIENTS AND METHODS: In all, 20 patients (16 male; age range 17-67 years) were studied prospectively; 12 had a reconstructed bladder. All had progressive loss of renal function with a glomerular filtration rate (GFR) of >15 mL/min. The study was in three parts: a baseline (99m)Tc-mercapto-acetyltriglycine (MAG3) scan was performed with an empty bladder, then a combined full bladder cystometrogram (CMG) with (99m)Tc-MAG3 study was done supine, and finally repeated in the sitting position. The pressure and volume changes together with the (99m)Tc-MAG3 scintigraphic variables with and without a full bladder were compared. RESULTS: Of the 17 patients with normotensive bladders, 13 (77%) had functional obstruction of the kidneys with a full bladder. In seven this was threshold dependent and occurred at a total mean (range) bladder volume of 348 (135-720) mL for both positions. In the other six patients there was minimal drainage of isotope from the kidneys even with the bladder empty. When the sitting position was compared with supine, gravity was more important for upper tract drainage in the reconstructed bladders. In five patients the detrusor pressure at which drainage began was close to zero. CONCLUSIONS: In 13 of 17 patients (77%) the kidneys failed to drain with a full bladder despite 'normal' detrusor pressures. It remains to be seen whether bladder emptying designed to keep the urine volume below the obstructing threshold volume will prevent further loss of renal function.