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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. 
If you treat mCRPC you need to know about mismatch repair. I don’t say this often, but it could be a matter of life or death. And that is not an exaggeration.

Ok, now that I have your attention, let’s talk about the science, the clinical care and the implications for the field.

But first, a brief case. Consider my patient Arnold (not his real name). He is a 68-year old man who underwent radical prostatectomy in 2011.
Late last November Bayer issued a press release notification of the premature halting of a study in which abiraterone and prednisone plus radium-223 was being compared to abiraterone and prednisone alone (ERA 223, NCT02043678). The announcement revealed that the study was being terminated early due to an imbalance in fractures and survival between the two arms – favoring the control arm
One of the biggest misconceptions in all of cancer care and oncology is the notion that a solid tumor ‘recurs’ after local therapy. If, as is often stated, ‘we got it all’ during surgery, then how can a cancer recur? The answer of course is that it was there all along. But that’s only the beginning of the story.
Cancer can limit one’s physical activity. Can physical activity limit one’s cancer? I’ve become a convert to thinking that it is possible that it can. I’m not convinced yet, but a few years ago I decided that it was worth my time and effort to study it. Compelling patient stories stick with us. I’ll never forget the story of a patient of mine who died several years ago. Let’s call him Dan.
Cell-free DNA analysis may improve the scalability of genomics for prostate cancer.  The management of CRPC has long been plagued by the inability of clinicians to get an accurate sense of the underlying biology of the tumor that they are treating. 
The flurry of media recently in reaction to Senator John McCain’s diagnosis of glioblastoma multiforme, a highly malignant brain tumor, touched right at the heart of where cancer fits in the American psyche:  That it is a battle to be won.

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