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A highly practical and interesting study, CARD, was recently presented at ESMO and published in the NEJM. It’s a study that answers a lot of questions, creates a few others, and can be translated into the clinic relatively quickly.

The CARD study randomized patients with castration-resistant prostate cancer (CRPC) to either treatment with cabazitaxel  ( taxane chemotherapy) or a second ‘sequence’ of androgen receptor (AR) targeted therapy (ARTT) – enzalutamide in patients with prior abiraterone exposure, or vice versa.

Treating cancer is hard. Its even hard when you have years of experience and are considered an expert. 

Communication with patients is always a challenge, as is gathering all the information you need to make an informed decision. Then there’s the energy and time that are required to keep up with the clinical literature in your space, and the scientific/basic literature of it if you are so inclined. 
I continue to be surprised by the biology of prostate cancer, and how much guessing we are still doing. The good news is the number of tools in the tool chest is increasing. Also, even in situations where they don’t direct our actions, our ability to gain an understanding of the molecular underpinnings of the disease may inform our discussions with patients.
I recently followed a minor twitter based jousting match between various cancer treating specialists about how we present the goals of care to patients. The conversation went something like this (on Twitter):

1. Dear Surgeons - stop telling patients “We got it all” signed, Medical Oncologists.
2. Dear Medical Oncologists – please inform your patients that your treatments for metastatic disease are palliative, not curative. Signed, Surgeons and Radiation Oncologists.
I have been thinking a lot about the outliers, the exceptional responders, those rare patients for whom we have cracked the code and end up with a PSA of zero after we treat them with abiraterone, immunotherapy or other treatments - and what to do about them.
I have stated many times in this forum before that treating castration-resistant prostate cancer (CRPC) is analogous to trying to hit a moving target. The better we get at treating it, the more the disease is able to evolve and adapt and acquire new mechanisms of drug resistance and lethality.
I love the year-end lists and the person of the year articles that always come out at this time. whether it is TIME magazine or Sports Illustrated or even People magazine (…not that I follow the worlds sexiest man and woman contest that closely), they help us give a perspective of the shifts in our world that occur within a year.
I just returned from a tremendously insightful meeting at the National Cancer Institute on the lineage plasticity of prostate cancer. The focus of the meeting was the myriad changes that systemic treatment induces in prostate cancer over time – most notably the emergence of neuroendocrine/small cell prostate cancer. I’ll address this entity in a subsequent entry. Before that, though, the striking focal point of discussion at the meeting was a single molecule -RB  ( or, the retinoblastoma gene)
Earlier this year I wrote a piece on the need to learn from the ERA-223 experience and pitched it in the context of the Apollo 13 moon mission, dubbed a “successful failure’ because it revealed a variety of problems in the space mission and created the opportunity to revise process based on continued close scrutiny of the data*. At ESMO 2018, the closer scrutiny of ERA-223 has indeed delivered some new information about our best practices in mCRPC.
Here’s some interesting science to follow and think about in the context of mCRPC treatment. – how cancer and cancer treatment will influence and even accelerate aging – and what we can do about it.

My institution, the University of Minnesota, recently launched a “Medical Discovery Team on the Biology of Aging” a program that brings together clinicians,
If things were different, I might be writing this blog about using Selinexor in prostate cancer.

Or,  I might be working on the design of the phase III study of BEZ235 in mCRPC, or the use of AMG-102 plus mitoxantrone in patients following docetaxel for mCRPC.
A new diagnosis of metastatic prostate cancer is life-altering.  Deciding on the treatment used to be straightforward but it’s not anymore. After addressing this issue with patients for many years, and staying abreast of the latest developments, I describe an approach to starting treatment in five questions for both the patient
Ever since they were introduced, the question of the efficacy of a combined approach with abiraterone and enzalutamide has been questioned.  We are now getting to the point of seeing the results of these approaches and a window into how similar, or distinct, these two therapies are.
I quip sometimes when lecturing that a clinician will make their first decision to use a new therapy based on the data - but the second time they make the decision to use that therapy it will be based on their experience. Although obviously a gross oversimplification,  I think it does reflect the fact that we obtain biases as we treat patients. 
The standard of care for castration-resistant prostate cancer (CRPC) has changed so much in the past decade that it is sometimes hard to keep up with what might be coming down the pipeline. The TROPIC Study, when it became public back in about 2011, was a complete surprise to me. The first I heard of the study was when the trial reported out the survival data and almost
Hormonal signaling is an intriguing process with a lot of redundancy, promiscuity and feedback. Androgen metabolism is particularly complicated and likely reflects the absolute necessity of intact hormonal signaling for mammalian evolution. I have spent over 15 years studying many aspects of prostate cancer but probably the two most prominent facets of my research life relate to the development of treatments like abiraterone for mCRPC but also the study of the measure of hormones, their signaling patterns and its relationship to outcome in CRPC.
The age of tumor sequencing is here. Does it help? Earlier this year a paper in JAMA oncology permitted us to begin to ask that question aloud. Oncology has doubled down on the promise that cancer therapy decisions are going to be personalized. That promise has been made to the public, professorships have been established and whole

A meditation on the need and utility for Sip T in 2018. On a nearly weekly basis I am confronted by the question of whether I should be giving a patient Sipuleucel T. I still use it, but not in all my CRPC patients, and I like to think of this therapy as having a reasonable benefit for patients - who are at an early point in the CRPC spectrum. I will explain but first let’s review the data and its limitations.

My first book, The Virility Paradox,  came out in February. I have written about it before and an interview with me ( by UCSD Urologist Kelly Parsons) has been posted elsewhere on UroToday. It has been a four-year project and, perhaps a bit melodramatically, I’ll use an overused word and call it a four-year ‘journey’. Here I want to focus on how that process changed me as a physician and affected my care of patients. Hopefully, there’s a lesson here for other clinicians and patients.
The ASCO Genitourinary Cancers Symposium for 2018 will feature the presentation of two-phase III studies of AR directed therapy in patients with non-metastatic CRPC. Before we get these results we can reflect on why these two studies were done in this patient population in the first place, and what exact clinical need is being addressed by the development of the studies in this space. 

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