including the need for numerous repeat surveillance biopsies. In this issue of the BJUI, Gallagher et al. [1] report the outcomes of an AS programme using selective repeat biopsy based on multiparametric MRI (mpMRI) and PSA dynamics. The authors address the important issue of whether mpMRI can be used to safely avoid repeat biopsies in AS protocols.The evidence for repeat biopsies in AS is based on studies from the pre-MRI era, where up to 30% of men were upgraded on repeat systematic TRUS biopsy [2]. It has been established that TRUS biopsy is a highly unreliable test and misses a substantial proportion of clinically significant disease. The current approach requiring the repeated application of an unreliable test will not improve the systematic error inherent to the test. It is clear that the pathway needs to be updated for the mpMRI era, and the cohort of men in Gallagher et al.[1] provides valuable reallife clinical data of an mpMRI-based AS programme with a unique 4-year follow-up period.The results are encouraging, with upgrading occurring in only 1.8% of men with a prior negative MRI. With follow-up, progression to radical treatment was 12.8%, which is consistent with the established diagnostic performance of mpMRI. The authors seek further improvements by investigating if PSA dynamics can identify men with a negative MRI at risk of progression. They find that PSA velocity is strongly associated with subsequent progression (AUC 0.95, P < 0.001) and conclude that men on AS with low-risk disease can safely avoid biopsy in favour of MRI, PSA monitoring and selective re-biopsy.This study [1] supports a growing body of evidence that mpMRI may be adopted as the primary surveillance tool for men on AS. The finding regarding PSA velocity should be interpreted carefully as it contrasts with previous studies, which found that PSA dynamics have a limited role as independent predictors of disease progressions in AS [3]. A non-invasive alternative to biopsy would be a valuable addition to AS and improve its acceptability as a management option. The burden of repeat surveillance biopsies for men on AS should not be underestimated. Indeed, in the present study~30% of men declined biopsy in favour of continued mpMRI surveillance.The question is can we adapt our current standard AS approach for the mpMRI era? There are still many challenges and many unanswered questions. The cost-effectiveness of mpMRI surveillance programmes needs to be established and the lack of MRI capacity remains a significant obstacle in introducing mpMRI pathways. The optimal imaging interval and the natural history of mpMRI lesions are just a few of the questions that need further research. These are exciting times to be a researcher in this field and there is much work to do as we start to build the new evidence-base covering all the questions required for the mpMRI era. References 1 Gallagher KM, Christopher E, Cameron AJ et al. Four-year outcomes from a multiparametric magnetic resonance imaging (MRI)-based active surveillance programme: PSA d...
Background
Human prostate cancer cells are routinely maintained in media supplemented with 10% Fetal Calf Serum (FCS) to provide androgen. In the present study, total and free testosterone levels in 10%FCS supplemented tissue culture media were determined and compared to levels in intact and castrated human males. Dextran-coated charcoal stripped FCS (i.e., DC-FCS) is often used instead of FCS to minimize the level of androgen provided in 10% serum supplemented media. Therefore, total and free testosterone levels in 10%DC-FCS containing media were likewise determined.
Methods
Total testosterone, free testosterone, and total dihydrotestosterone (DHT) were determined on RPMI-1640 media supplemented with either 10%FCS or 10%DC-FCS by ELISA assays before and after exposure to LNCaP human prostate cancer cells in culture. The growth and PSA secretion by these cells was also determined.
Results
10%FCS supplemented media contains a castrate level of testosterone. However, even with this castrate starting level of testosterone, LNCaP cells concentrate and metabolize the testosterone to produce a physiologic (i.e. 10 nM) level of intracellular DHT which optimally stimulates the growth of these cells in vitro.
Conclusions
The present studies document that prostate cancer cells auto-regulate their androgen metabolism so that an optimal level of DHT for growth is maintained during both up and down fluctuations in the supply of testosterone. These results have significant implications for whether exogenous androgen should be added to the 10%FCS supplemented media to grow prostate cancer cells from intact vs. castrated patients.
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