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Article of the Week: Co-introduction of a steroid with docetaxel chemotherapy for metastatic castration-resistant PCa affects PSA flare

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

Co-introduction of a steroid with docetaxel chemotherapy for metastatic castration-resistant prostate cancer affects PSA flare

Masaki Shiota*, Akira Yokomizo*, Ario Takeuchi*, Keijiro Kiyoshim a*,Junichi Inokuchi*, Katsunori Tatsugami*, Ken-ichiro Shiga, Hirofumi KogaAkito Yamaguchi, Seiji Naito† and Masatoshi Eto*
*Department of Urology, Graduate School of Medical Sciences, Kyushu University, and Division of Urology, Harasanshin Hospital, Fukuoka, Japan

Abstract

Objective

To investigate the potential relationship of steroid usage with prostate-specific antigen (PSA) flare as well as the prognostic impact of PSA flare, which is known to occur in 10–20% of patients with metastatic castration-resistant prostate cancer during docetaxel chemotherapy. In the world of fat-burners, Clenbuterol has a place of importance among bodybuilders and others. Several athletes also utilize the drug for its long list of potential benefits. While great care should be taken with something like this, there are nonetheless some advantages that should be considered. For example, understand that Clenbuterol is not a steroid, Red Thai Kratom is one of the most widely used for beginners.

Patients and Methods

This study included 71 patients with metastatic castration-resistant prostate cancer treated by docetaxel chemotherapy with co-introduction of a steroid. PSA flare was defined as a transient PSA increase followed by a PSA decrease.

aotwdec2-results

Results

PSA flare was recognized in 7.0–23.9% of patients according to the definition used. Intriguingly, men with steroid intake before the initiation of docetaxel chemotherapy experienced significantly fewer PSA flares. The progression-free survival rate in men with PSA flare was equivalent to that of PSA responders, but significantly better than men with PSA failure.

Conclusions

Our results suggest that de novo steroid co-introduction with docetaxel chemotherapy induces the PSA flare phenomenon. This novel finding may account for the mechanism of PSA flare as well as being valuable for distinguishing PSA elevation attributable to PSA flare from that attributable to PSA failure.

Editorial: What is behind the flare phenomenon?

In the present issue of BJUI, Shiota et al. [1] propose a potential explanation for the PSA ‘flare’ observed in many patients as they initiate docetaxel chemotherapy. The PSA flare or ‘surge’ phenomenon has been noted for years, and may affect up to one-fifth of patients treated with docetaxel. Multiple reviews have concluded that the development of flare does not influence disease-specific outcomes [2, 3], which is further supported by the present paper [1]. However, there are no pragmatic analyses of how this flare is interpreted in real-world practice. As treatment of prostate cancer becomes more complex, and definitions of progression on treatment continue to evolve, practitioners must be aware of this laboratory pattern to avoid unnecessary discontinuation of therapy based on early PSA change alone.

The cause of such flare has only been postulated. Many suggest that it could be caused by PSA release from lysed cells or by aberrant androgen receptor (AR) activation, but other theories are also proposed. The present paper supports the hypothesis that transactivation of the AR by corticosteroids contributes to the flare. Further translational work may provide additional insight into this mechanism, but we have long discussed the influence of steroid administration on the AR. Similar flare phenomena have been observed with cabazitaxel [4] and abiraterone acetate, two regimens that are reliant on concomitant steroid use. Interestingly, patients in the present cohort treated with steroids before treatment initiation had less flare. This is a unique observation in that steroid activation may occur, but at an earlier time point, mitigating the coincidental rise when starting chemotherapy. Just as one must be aware of the existence of flare to avoid premature abandonment of a regimen, perhaps we now must take into account previous steroid use and interpret a PSA rise slightly differently. The present work is certainly hypothesis-generating and larger series may offer additional insight.

Recent data have shown significant survival gains using docetaxel in the hormone-sensitive metastatic setting, in which patients received chemotherapy without daily prednisone use [5]. Practitioners may find themselves managing patients on docetaxel chemotherapy who may or may not be taking corticosteroids. These recent data will probably also contribute to a ‘resurgence’ of sorts in the use of chemotherapy, and remembrance of the flare is important. We may find ourselves interpreting PSA flare in multiple steps: we will assess the agent (i.e. a taxane) and the use of prednisone (i.e. present prior to treatment or initiated at the start) and then interpret the results accordingly. The work of Shiota et al. in this observational study continues to highlight the flare phenomenon and the fact that the use of steroids before, or during, chemotherapy may further complicate our approach to the care of patients on chemotherapy. The field is moving forward and, as we work to understand the intricacies of PSA response, we also create more and more reliance on providers to really marry the art and science of medicine.

 

Elizabeth R. Kessler

 

Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, CO, USA

 

References

 

 

 

3 Nelius T, Klatte T, de Riese W, Filleur S. Impact of PSA are-up in patients with hormone-refractory prostate cancer undergoing chemotherapy. Int Urol Nephrol 2008; 40: 97104

 

 

5 Sweeney CJ, Chen YH, Carducci M et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med 2015; 373: 73746

 

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