Progress and Promise in Prostate Cancer
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The PARP Partnering Predicament
The Progression-Free Survival to Overall Survival Connection. How to Interpret – and Why
If a therapy in castrate-resistant prostate cancer (CRPC) shows an improvement in progression-free survival, but not overall survival, should that change practice? The topic is top of mind for us this month based on the results of the ACIS study presented at the ASCO GU 2021 Genitourinary Cancers Symposium by Dana Rathkopf of Memorial Sloan Kettering – and I’ll explore it here. To briefly recap, ACIS compared abiraterone to abiraterone plus apalutamide in men with chemotherapy naïve CRPC.
2020 Hindsight and 2021 Foresight
By all accounts outside of our world of prostate cancer, 2020 was a pretty bad year. That much has been decided and agreed upon by just about everyone in the world. With that said, 2020 was not a horrible year in the progress against prostate cancer. Several new developments arose and progressed in the past year that can give us hope and new options for patients. Along those lines, it can give us an optimistic look at 2021 as well, as the developments of 2020 are but a precursor to some of the moments that may await us in 2021.
Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treatment Yields to Promise and Progress
I am grateful to UroToday for giving me the platform that this Center of Excellence allows. I have dedicated my career to the care of men with metastatic castration-resistant prostate cancer (mCRPC), the development of therapies to treat it, and (hopefully) thoughtful analysis of the biological, clinical, and even societal factors that characterizes it. A forum to generate and share ideas is a gift.
Timepoints on the Same Journey, or Two Different Journeys? - Thoughts on De Novo vs. Metastatic Prostate Cancer
"When does a radical prostatectomy save a life?" is a question that has been asked in the medical literature. Studies from Scandinavia1 reported long term outcomes of a randomized trial of immediate radical prostatectomy versus observation and deferred treatment. The study evaluated the outcome of overall survival (OS) and showed that OS curves remained superimposed until the timeframe of year 10-15, suggesting that the ‘saving a life’ prostatectomy was occurring around year 15.
Racial Disparities in Prostate Cancer Outcomes: Biology or Society?
The tumults of 2020 have put racial disparities front and center for the nation at large and health disparities are now viewed with increasing intensity, if not clarity. Prostate cancer patients and the treating community have struggled with the question of racial disparities in outcome for some time, and recent events bring this closer to the front of our dialog.
Wherefore Art Thou, Radium?
I was confronted with a decision in the clinic this week about whether or not to use radium-223 for a patient with metastatic castration-resistant prostate cancer (mCRPC). He was on the older side, mid to late 80’s and his performance status was declining rapidly. He had persisted for quite some time with relatively low volume disease, in fact, just pelvic lymph nodes. As those progressed, he developed urinary outlet obstruction (even though the nodes weren’t that big) with multiple urinary tract infections (UTI) and, during a several month period marked by brief hospitalizations, relatively rapid failure of next-generation androgen receptor (AR) antagonists, all amidst the COVID-19 (SARS-CoV-2) pandemic, metastatic disease in the bone blossomed in multiple sites, and it was associated with relatively mild pain.
PARP Inhibitor Resistance: Closing a Door, Opening a Window
With two poly ADP ribose polymerase (PARP) inhibitors on the market, we expect to see many patients on these therapies in the coming years, most likely with great benefit for a substantial proportion of them, prolonging life and delaying or preventing further misery from this disease.
PARP Inhibitors, Prostate Cancer and a Promise Fulfilled
June 26, 2020, marked the 20th anniversary of the publication of the first working draft from the Human Genome Project. At a special White House event to commemorate the results of this 10-year public effort (it was really more like 50 years since the discovery of DNA, but I digress), then-President Bill Clinton called the project “the most wondrous map ever created by humankind”, and touted its promise to detect, prevent, and treat disease. Obtaining that first sequence from one human cost about $2B and resulted from a massive global public/private partnership.
Is This the HERO We Need?
Another advance in hormonal approaches to controlling prostate cancer is available for our consideration. The results of the HERO trial demonstrate efficacy and safety advantages of oral relugolix when compared to standard of care leuprolide, given via intramuscular injection every three months. The results open up two areas for discussion: 1) is an oral ADT feasible, effective and necessary and 2) do LHRH antagonists confer cardiovascular and disease control benefits compared to LHRH agonists? It provides us with choice and a lot to ponder in terms of how this treatment may alter patient outcomes, practice patterns, and the future of our approaches to many stages of prostate cancer.
Targeting the AR: Have We Reached the Outer Limits?
Primary Tumors Can Tell Us More If We Ask Them To
As a medical oncologist, I may rely a little less than my radiation or urology colleagues on the Gleason score for prognosis and treatment decision making. Most of our decisions are based on the pace of disease and extent, and of course whether it is castration-resistant or castration sensitive. However, I do look at it and in particular, it factors into the data ‘stew’ that one creates within an individual case and how we approach it.
Early, Earlier, Earliest (Docetaxel)
Chemotherapy improves survival when given to patients prior to radical prostatectomy.
It is the latest, and potentially the last, piece of data in the decades-long march of this important and interesting (but much-maligned) therapy. Will this news change practice?
ATM: Time to Withdraw?
The clinical development of therapies targeting DNA repair pathways in prostate cancer is now well underway. It is a hopeful on-ramp for prostate cancer into the world of molecular oncology. We are beginning to see the emergence of consistent data and some surprises. There is a significant reason for hope, for example, that the poly ADP ribose polymerase (PARP) inhibitors will become a standard of care for patients with BRCA1 or BRCA2 alterations.
How Do We Play This CARD?
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.
Minding the Gaps in Prostate Cancer Treatment
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.
Hormone Sensitive Metastatic Disease: The Glass is 25-33% Empty
Preserve! Prevent! Prolong! (Embrace These as the Goals of Care)
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.
What Should We Do with the Exceptional Responders?
Small Cells, Big Worries
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