Expert: Precision medicine shaped progress across urologic oncology in 2025

Several significant advancements have emerged across urologic oncology over the past year, ranging from the expanding role of PARP inhibitors in prostate cancer to the evolving treatment strategies for BCG-unresponsive non–muscle invasive bladder cancer. In the following interview, Joshua Palka, DO, a urologist at the Michigan Institute of Urology, reflects on the key trends that shaped the field in 2025, emphasizing the growing role of precision medicine across disease states.

Palka discusses how advances in biomarkers, genomic testing, and AI-driven diagnostics are influencing treatment selection and sequencing in prostate, bladder, and kidney cancers. Moving forward, he points to the importance of personalized care and multidisciplinary collaboration in treating patients with urologic cancers.

Urology Times: What were some of the key themes that defined the urologic oncology space in 2025?

Palka: 2025 really can be summed up by one thing, and that's precision medicine. [This year we saw] different biomarkers and [efforts] to determine which systemic therapy to use at the right time, rather than what we've done in the past with a more shotgun approach. One example of this is in BCG-unresponsive bladder cancers, where we’re focused on how to sequence new agents. Additionally, in the world of prostate cancer, there’s the evolving role of PARP inhibitors and genomic testing, whether that be through blood testing or through tumor somatic testing. And then finally, with kidney cancer, we’re trying to tease out the role for triplet therapy in patients with advanced kidney cancer.

Urology Times: What advances in prostate cancer management have stood out most to you this year, especially looking at the metastatic or hormone-sensitive settings?

Palka: What's been an exciting area of interest for prostate cancer, mainly with metastatic castrate-sensitive or castrate-resistant cancer, is the use of PARP inhibitors and the use of PSMA-directed therapies. The evidence is becoming more solidified with PARP inhibitors, especially for BRCA1 and BRCA2 patients, where it can be used in combination with therapies, but also now as a possible monotherapy. Identifying which patients are going to achieve deep and meaningful responses, rather than broadly applying these treatments, [is important].

Additionally, with the radioligand therapies, there's a lot of interesting trials that we're a part of with other academic centers in the area, looking at different ways to direct our treatments specifically to where the cancer is. The theme, again, is that precision medicine is becoming more and more ever present.

Urology Times: How are you currently integrating genomic testing into your treatment decision making? How do you see the role for this evolving into the future?

Palka: Now that we have these newer agents available to us, we need to decide when and where should we be using them. At least in my practice, we utilize the role of genomics very strongly upfront, especially in patients who are not only high risk, but also metastatic. We partner with the local testing industry to identify these patients quicker and continue to reevaluate them during their treatment. The future lies in composite biomarkers, looking at different transcriptase signatures within either somatic testing or genomic testing. A lot of these tests are going to become the forefront of how we test and how we treat these patients, and also how we allow them to have a sense of what the future may hold for them.

Urology Times: Shifting to the bladder cancer space, we've seen remarkable progress, particularly in the non–muscle and muscle-invasive setting. What are some of the most practice changing updates from 2025?

Palka: This is where I've seen the most growth and the most excitement in the world of urology. The age-old question is, what do you do with these non–muscle invasive bladder cancers that do not respond to BCG? In the past, we had very few options in terms of chemotherapeutic agents, and to be frank, they just didn't work great. We now have the tools to treat these patients, including utilizing immunomodulators for these non–muscle invasive bladder cancers. We're also trying to figure out how to sequence these agents, rather than BCG upfront. That's really the excitement: trying to find out where these medications find their role for these patients.

In the muscle-invasive setting, we’re looking at neoadjuvant and now adjuvant treatment options for these patients. In 2024, they came out the NIAGARA protocol, and now we’re utilizing these immunomodulators and antibody drug conjugates to prolong patients’ progression-free survival and overall survival as well.

Urology Times: You mentioned the wealth of options in the BCG-unresponsive setting. What are some of the unmet needs in that area regarding treatment sequencing or patient selection?

Palka: This is where we have a cornucopia of different options available to us now. The question is, which of these do we apply upfront? Which is going to be the best for our patients? What's exciting is that there's a lot of new testing in this space that's being released, not only through clinical trials, but also through industry. We're partnering with a newer group, Vesta, utilizing AI technology to identify in the tissue specimen, with different signatures, which patients may benefit more from upfront BCG vs gem/doce upfront as intravesical therapy. As we continue to utilize these tests, we're going to be able to identify these patients quicker and identify which treatment options are going to benefit them. It all goes back to initially what we talked about, that precision is the key now. In the past, it was more of a shotgun approach to see what happens and then identify those who may have failed those treatments.

Urology Times: Looking at the kidney cancer setting, what are some of the biggest takeaways from recent RCC trials, particularly around perioperative or adjuvant therapy?

Palka: This is another area of interest of mine, where you have a patient who has high-risk advanced disease and you want to reduce their risk of recurrence. Initially, we were very excited about using immunotherapy post-operatively. However, what we're finding is that what really matters is not necessarily utilizing it for everybody, but that risk stratification is important for these patients. While immunotherapy is generally well-tolerated, it's not without its own risk. We want to ensure that these patients who would benefit from this therapy are identified early, and the medications that are available to us are utilized appropriately for these patients. We [are aiming to] reduce toxicities while gaining the benefit that comes along with these therapies in the adjuvant and then also possibly the neoadjuvant setting in renal cell carcinoma.

Urology Times: How do you interpret some of the evolving data on triplet regimens? What role do you see for these regimens in practice?

Palka: This was met with a great deal of excitement initially, when these trials were being read out. The utilization of both doublet and triplet therapy was possibly a new option for these patients, who don't really have a lot of options available to them. While the more recent trials for triplet therapy do show somewhat of an improvement for progression-free survival, the overall survival hasn't been shown to be as exciting. It again measures up to patient selection, where the intermediate-risk patients were the ones that benefited most. So, while we have these therapies available to us, what's going to matter most is patient selection. We need to utilize them appropriately in these patients. It'll be interesting to see the outcomes as these trials continue to read out. But triplet therapy has been seen to have substantially higher toxicity than doublet therapy, so it may not be necessarily that the medication doesn't work, it's just that the patients are unable to tolerate the toxicity, especially in the most recent trials.

Urology Times: What are some of the areas that you are most optimistic about in the next few years, whether it be biomarkers, novel combinations, or other emerging trends?

Palka: We're going to see an explosion, not only within clinical trials, but also within industry, looking at biomarkers that are going to be more personalized to the patient. Not only can biomarkers tell us which treatment to use, but also the order in which we should use these treatments. Again, we have so many options available to us, so the question is what is going to benefit the patient the most? Diagnostic tools are going to be the key to improving these treatment modalities. What's going to be a fun and exciting thing to see over the 5 to 10 years is when a patient comes to me with a certain diagnosis, I'm going to be able to make a personalized approach for that patient's treatment plan. I'm really excited to see that in the future.

Urology Times: Are there any ongoing trials that you are most eager to see results from moving into the new next year?

Palka: The most exciting things that I'm looking at are the trials looking at muscle-invasive bladder cancer and non–muscle invasive bladder cancer, particularly the combination and sequencing of immunotherapy in addition to chemotherapy, both neoadjuvant and adjuvant. I'll be interested to see what paradigm shifts these are going to bring, similar to how the NIAGARA protocol brought back in 2024.

Additionally, I'm very interested to see how PARP inhibitor use is going to be sequenced, whether it's going to be becoming a more frontline therapy in patients who are BRCA1- or BRCA2-positive, or any of the other HRR mutation positive. We may be able to [achieve] a durable response much more quickly, rather than waiting until they have failed multiple other treatment modalities.

Urology Times: Is there anything else that you’d like to add?

Palka: What excites me more than anything is the multidisciplinary approach with these patients. We have a lot of different options available to us, so we’ve been able to utilize urologists and urologic oncologists for surgery, radiation oncologists for radiation therapies, and also medical oncologists and pathologists looking at biomarkers and identifying which sequencing is going to be most important. The biggest thing is that it's going to be more of a team effort, rather than everybody individually on an island treating patients.