Why are pretreatment prostate‐specific antigen levels and biochemical recurrence poor predictors of prostate cancer survival?

Abstract

An ultra scale‐down (USD) device that provides insight of how industrial homogenization impacts bioprocess performance is desirable in the biopharmaceutical industry, especially at the early stage of process development where only a small quantity of material is available. In this work, we assess the effectiveness of focused acoustics as the basis of an USD cell disruption method to mimic and study high‐pressure, step‐wise homogenization of rec Escherichia coli cells for the recovery of an intracellular protein, antibody fragment (Fab′). The release of both Fab′ and of overall protein follows first‐order reaction kinetics with respect to time of exposure to focused acoustics. The rate constant is directly proportional to applied electrical power input per unit volume. For nearly total protein or Fab′ release (>99%), the key physical properties of the disruptate produced by focused acoustics, such as cell debris particle size distribution and apparent viscosity show good agreement with those for homogenates produced by high‐pressure homogenization operated to give the same fractional release. The only key difference is observed for partial disruption of cells where focused acoustics yields a disruptate of lower viscosity than homogenization, evidently due to a greater extent of polynucleic acids degradation. Verification of this USD approach to cell disruption by high‐pressure homogenization is achieved using USD centrifugation to demonstrate the same sedimentation characteristics of disruptates prepared using both the scaled‐down focused acoustic and the pilot‐scale homogenization methods for the same fraction of protein release. Biotechnol. Bioeng. 2012; 109:2059–2069. © 2012 Wiley Periodicals, Inc.

A Comparison of the Prognostic Value of Early PSA Test-Based Variables Following External Beam Radiotherapy, With or Without Preceding Androgen Deprivation: Analysis of Data From the TROG 96.01 Randomized Trial

“…Its value in predicting survival is less clear, however. Like many other investigators, we have also found the iPSA level to be a good predictor of biochemical failure-free survival (BFFS) in the TROG 96.01 dataset (3,7). However, in this same dataset, the iPSA level did not predict PC-specific survival (PCSS).…”

“…In the same dataset, we found that the occurrence of biochemical failure itself, however, is a far weaker predictor of cancer death than time to biochemical failure (3).…”

Does prostate-specific antigen nadir predict longer-term outcomes of prostate cancer after neoadjuvant and adjuvant androgen deprivation therapy in conjunction with brachytherapy?

“…The two reasons for hormone manipulation were (1) to downsize the prostate, as in most cases the gland was considered too large for needle placement. If gland size had not reduced to a transverse width of less than 5 cm by that time, they were switched to EBRT alone; (2) in the context of a novel technique, the use of hormones in the lower risk groups was deemed to be a safer approach. Brachytherapy was delivered before EBRT in most cases.…”

“…The current Phoenix consensus definition of biochemical failure after external beam radiation therapy (EBRT) or brachytherapy with or without hormonal therapy (HT) is a rise by 2 ng/ mL or more above the nadir PSA (nPSA) (1). However, biochemical failure itself has a poor specificity for predicting subsequent cancer death (2); and given the slow natural history of PC, many post-treatment years may have passed before biochemically relapsed disease becomes clinically apparent. Hence, study into various other PSA response patterns have aimed to provide earlier and more accurate surrogate endpoints of long-term outcomes.…”

Biochemical Recurrence: A Valuable Endpoint?

“…In the same dataset, Denham and colleagues also determined how the occurrence of biochemical failure itself related to prostate cancer-specific mortality and demonstrated that the occurrence of biochemical failure was a far weaker predictor of cancer death than time to biochemical failure (Denham et al 2009). It was also shown that prognostic factors for early cancer death changed dramatically at biochemical recurrence.…”