Despite the growing availability of effective agents in the metastatic castration-resistant prostate cancer (mCRPC) treatment arsenal, suboptimal treatment patterns and ensuing gaps between therapeutic advancements and real-world patient outcomes persist, according to Jue Wang, MD.
In his presentation delivered during a recent OncLive® State of the Science Summit™ on genitourinary cancers, Wang illustrated these real-world challenges through a series of clinical case scenarios, highlighting the importance of utilizing dynamic, biology-driven treatment strategies to improve outcomes and underscoring the limitations of rigid sequencing approaches. He also noted factors that contribute to the underutilization of existing therapies, including treatment-related toxicity, access barriers, and provider-level decision-making.
“Cancer care delivery is not just about implementing clinical trial protocols; it is a reinvention,” Wang stated in an interview with OncLive. “We must look at those data, [consider] what we know and what we don’t know, and put the patient at the center [of our decision-making].”
In the interview, Wang outlined the rationale for his presentation, discussed the implications of current treatment patterns in mCRPC, and proposed a reimagined framework for treating prostate cancer in everyday practice.
Wang is a professor in the Department of Internal Medicine and a member of the Division of Hematology and Oncology at the University of Texas Southwestern Medical Center in Dallas.
OncLive: What are some of the challenges clinicians face when translating therapeutic advances into real-world treatment approaches, and might they be addressed?
Wang: Even in 2025, mCRPC is an incurable disease. It’s a lethal disease [and] very hard to treat. Clinical decision-making is the nucleus of oncology. It’s very hard and complex. I decided to cover the complexity of why this cancer is so hard to treat, and why, despite our amazing advances in the last 2 decades with many new medications and different strategies, real-world outcomes show that there is a disconnect between new advances and how we actually utilize those drugs.
I started by showing the suboptimal treatment patterns [in mCRPC]. Many patients [with this disease] cannot receive life-prolonging therapies that are already [available], and some patients only receive 1 or 2 treatments. [Accordingly, an increasing number] of these patients drop off after each line of therapy. Besides financial toxicity and disparities in access [to care], I focused on what providers, from a cancer delivery standpoint, can do to make a difference and improve outcomes.
In the second part [of my presentation], I provided some real-world clinical scenarios to illustrate the real-world challenges [with mCRPC management], which are much harder than the simplified version seen in clinical trials. I showed how we can strategically use our current knowledge of disease resistance and patient-centered care to improve outcomes and treatment strategies.
How has treatment sequencing evolved in mCRPC with the advent of precision medicine?
Addressing these complex challenges in this evolving disease is a moving target. The number 1 issue is that when patients move from the castration-sensitive to castration-resistant setting, they’ve already experienced a lot of treatment. Such treatment either kills the cancer cells or pushes them towards [disease] resistance.
[Discussions about treatment sequencing] are not like they were before. Our guidelines give a menu of drugs to choose from, but it’s not that simple. [Over the last 10 years, we’ve seen a shift towards precision medicine,] with molecular imaging and testing to guide us in developing individualized strategies rather than [rigidly thinking] about sequencing by just pulling one drug after another. That was the old strategy, which worked when we didn’t have many options. Now, with so many life-prolonging treatments available, a better strategy will impact outcomes.
The real-world data show us that just having many available agents does not automatically lead to improved patient outcomes.
What can be learned from the first case study you presented?
The first case I presented just showed a patient’s approximately 8-year journey with mCRPC. He [first presented] in the localized and hormone-sensitive setting, so the total journey was [technically] 12 years. Initially, he had high-risk prostate cancer that was removed, but after prostatectomy, he had a persistent tumor marker. [His] prostate-specific antigen [PSA] levels were rising and he received several good treatments, but eventually the cancer continued to progress. At the beginning, he had a Gleason score of 9 [coupled with lymphovascular invasion]. Between 2017 and 2018, he developed mCRPC.
[Using this case study], we tried to show how we can strategically time treatments to make an impact. Recent publications have shown that real-world patients with mCRPC survive approximately 2 to 3 years. However, this patient is already 7 years in, is still going strong, and is looking for new treatment.
This shows that instead of using a rigid sequencing, we should consider the real-world scenario. Patients usually start with an androgen receptor signaling inhibitor [ARPI], and sometimes even receive another one back-to-back. That’s because both the physician and the patient perceive those treatments as very safe and easy to administer. They don’t require a lot of scheduling or intravenous administration, so for the sake of convenience, we end up ignoring what we currently know about cross-resistance.
My advice from that entire case story is not to put all of one’s eggs in one mechanistic basket. Instead, we should strategically rotate medications based on the pace of the disease.
Later, this patient developed a new liver metastasis after many years of undetectable PSA. A biopsy showed neuroendocrine transformation- it was a different cancer. It demonstrated lineage plasticity under treatment pressure. We gave treatment specific to that phenotype because we had biologic information. The patient received chemotherapy, immunotherapy, and prostate-specific membrane antigen–targeted therapy, in addition to other ARPIs. He also received PARP inhibitor therapy and maximized his participation in clinical trials. Seven years into his mCRPC journey, his PSA level began to rise again. Another biopsy showed that he was switching lineage again—this time to prostatic adenocarcinoma.
Overall, this case study shows how much we don’t know, and how much we assume we know. Our [approaches to] treatment should be biologically informed, monitored in real time, and be therapeutically adaptive.
How can oncology education and case-based learning better reflect the real-world complexity of treating patients with mCRPC, especially considering evolving disease biology and treatment resistance?
I have many patients working in other professions—painters, plumbers. Sometimes I ask them, how they got their skills. They never say, ‘I reviewed the ASCO slides or industry-sponsored slide decks to gain the skills.’ They never review the transportation laws alone to [teach drivers how to drive].
Clinical scenarios reflect real-world complexity. Patients in clinical trials usually have good performance status, but real-world patients can have variable performance status. Clinical trials simplify the answer by having strict enrollment criteria, so the patient population is homogeneous. These clinical trial [populations] are the vast majority [represented in academic datasets].
