Case selection for radical prostatectomy in the UK

INTRODUCTION: Radical prostatectomy is an increasingly popular treatment option for clinically localised prostate cancer, yet PSA outcome figures are rare in the UK. This makes it difficult to establish appropriate criteria for case selection. We conducted an audit of PSA recurrence of 5 large centres in the south of England and investigated the use of pre-operative PSA to improve case selection and outcome. METHOD: 854 patients notes were audited for pre-operative staging parameters and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment as well as patients with incomplete data and follow-up were excluded. RESULT: Median follow-up was 52 months for the remaining 663 patients. Median PSA was 10 ng/ml. A large improvement of PSA recurrence free survival rates was observed from 1988 to 1998 as a result of change in case selection and stage migration. Overall Kaplan-Meier PSA recurrence free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. Five-year PSA recurrence free survival probability for PSA ranges <4 ng/ml, 4.1-10 ng/ml, 10.1-20 ng/ml and >20 ng/ml was 0.82, 0.73, 0.59 and 0.20, respectively (Wilcoxon, p < 0.0001). A simulation of biochemical recurrence free survival for patient cohorts with stepwise reduced inclusion PSAs suggests an improved outcome for patients with a pre-operative inclusion PSA of <12 ng/ml. Further reduction of the inclusion PSA does not improve outcome. CONCLUSION: Intermediate PSA recurrence free survival has improved over time in England. PSA recurrence free survival estimates are less optimistic compared to frequently quoted American figures. A reduced pre-operative PSA cut-off for case selection may be used to improve outcome.     

How long is urinary cytology abnormal after flexible cystoscopy?

OBJECTIVE: To examine the urinary cytological changes caused by flexible cystoscopy and provide clinical guidelines for a reliable time interval for urinary cytological examination after flexible cystoscopy. PATIENTS AND METHODS: Forty-eight patients attending for flexible cystoscopy were recruited into the study. Each patient was asked to provide eight urine samples before, immediately after and at 1, 2, 7, 14 and 28 days after cystoscopy. Cytospin preparations of the urine samples were made and slides stained using the Papanicolaou stain. Cytology was analysed while unaware of sample origin, by three different cytopathologists. RESULTS: The cytological changes were characterized by a striking increase in cellularity immediately after flexible cystoscopy, mostly accounted for by urothelial cells. Consistent morphological changes included the formation of 'columnar' cells, papillary clusters, increased nucleo-cytoplasmic ratio and nuclear atypia. These changes were transient, with most disappearing within a day of flexible cystoscopy. CONCLUSIONS: There are cytological changes, on voided urine cytology, after flexible cystoscopy but they were transient, and urine sent more than a day after flexible cystoscopy should be free from artefactual change caused by instrumentation. These results suggest that clinicians sending urine for cytological analysis should provide information about the nature and timing of any endoscopy so as to avoid false-positive interpretations of urine cytology by the cytopathologist.     

Time trends in case selection, stage and prostate-specific antigen recurrence after radical prostatectomy: a multicentre audit

OBJECTIVES: To report an audit of preoperative staging variables, case selection, stage migration and prostate-specific antigen (PSA) recurrence at five large centres in the south of England. To establish PSA outcome values after radical prostatectomy for clinically localized prostate cancer in the UK, and enable appropriate patient counselling. PATIENTS AND METHODS: The notes of 854 patients were audited for preoperative staging variables and follow-up data obtained. Patients with neoadjuvant and adjuvant treatment, and with incomplete data and follow-up, were excluded. RESULTS: The median follow-up was 52 months for the remaining 663 patients; the median PSA level was 10 ng/mL. There was a large migration towards lower PSA and stage; this translated into improved PSA survival rates. The overall Kaplan-Meier PSA recurrence-free survival probability at 1, 3, 5 and 8 years was 0.83, 0.69, 0.60 and 0.48, respectively. The 5-year PSA recurrence-free survival probabilities for PSA levels of < 4, 4.1-10, 10.1-20 and > 20 ng/mL were 0.82, 0.73, 0.59 and 0.20, respectively (Wilcoxon, P < 0.001). The PSA recurrence-free survival probabilities for biopsy Gleason grade 2-4, 5 and 6, 7 and 8-10 at 5 years were 0.70, 0.61, 0.55 and 0.21, respectively (Wilcoxon, P < 0.001). Similarly, the 5-year PSA recurrence-free survival probabilities for clinical stages T1a and 1b, T1c, T2a and T2b were 0.79, 0.62, 0.57 and 0.44, respectively (Wilcoxon, P = 0.0012). CONCLUSION: With better case selection the intermediate oncological outcome has improved over time in the UK. PSA recurrence-free survival estimates are less optimistic than the frequently quoted American values. The present values may be used to help in counselling British patients before radical prostatectomy.     

Leuprorelin acetate in prostate cancer: a European update

This review provides an update on leuprorelin acetate, the world's most widely prescribed depot luteinising hormone-releasing hormone analogue. Leuprorelin acetate has been in clinical use in the palliative treatment of prostate cancer for more than 20 years, but advances continue to be made in terms of convenience and flexibility of administration, and in the incorporation of leuprorelin acetate into novel treatment regimens. The drug is administered in the form of a depot injection containing leuprorelin acetate microspheres, and is at least as effective in suppressing testosterone secretion as orchiectomy. In patients with prostate cancer, serum testosterone levels are reduced to castrate levels (< or = 50 ng/dl) within 2-3 weeks of the first one-month depot injection of 3.75 mg or three-month depot injection of 11.25 mg. Both the one-month and three-month formulations are effective in delaying tumour progression and alleviating symptoms of locally advanced and metastatic prostate cancer. Tolerability is generally good, with side-effects reflecting effective testosterone suppression. Recent studies have investigated the place of leuprorelin acetate as part of continuous or intermittent maximal androgen blockade (MAB) and in neoadjuvant therapy (i.e. to reduce the size of the prostate and downsize the tumour before radiotherapy). Additional formulations and presentations are in development, including a six-month injection, with the aim of adding to the clinical flexibility and patient acceptability of this important palliative treatment for prostate cancer.     

Overexpression of vimentin: role in the invasive phenotype in an androgen-independent model of prostate cancer

The androgen-sensitive LNCaP prostate cancer cell line is less invasive than hormone-insensitive lines. CL1, an aggressive, hormone-insensitive LNCaP subline derived by continuous passaging in hormone-depleted medium, was compared with the parental cell line by cDNA microarray analysis. The gene coding for the intermediate filament protein vimentin was found to be highly up-regulated in the CL1 subline. This difference was confirmed by Northern and Western blots and visualized by immunofluorescence microscopy. To assess the contribution of vimentin to the invasive phenotype, LNCaP cells were stably transfected to overexpress vimentin, and the CL1 cells were transfected with vimentin antisense construct. The invasiveness of the transfected cells was tested using an in vitro invasion assay. We were able to demonstrate that decreasing vimentin expression in the constitutively vimentin-expressing CL1 cells led to a significant decrease in their invasiveness but that forcing expression of vimentin in the LNCaP cells did not augment their invasiveness. These findings imply that vimentin expression contributes to the invasive phenotype but cannot confer it alone.     

A comparison of the phototoxicity of protoporphyrin, coproporphyrin and uroporphyrin using a cellular system in vitro

The photobiological effects of protoporphyrin (PP), coproporphyrin (CP) and uroporphyrin (UP) were investigated using an in vitro model. Suspensions of Ehrlich ascites carcinoma cells were labelled with 51Cr and irradiated in the presence of a wide range of concentrations of PP, CP and UP. It was found that PP was the most potent photosensitizer in this system; CP was less effective than PP and UP was the least potent. The cell lysis by CP was enhanced by superoxide dismutase (SOD) and inhibited by catalase; the lysis by UP was also inhibited by catalase; on the other hand, the lysis by PP was not affected by SOD or catalase. These indicate that the cell lysis by CP and UP was largely due to hydrogen peroxide produced from superoxide formed during the irradiation. The lysis produced by PP was not mediated by hydrogen peroxide. These differences in the mechanisms of the phototoxicity of the various porphyrins may have relevance in the etiology and treatment of the porphyrias.