2026 AUA/SUO Advanced Prostate Cancer Guideline: Key updates and clinical FAQs

The American Urological Association (AUA) and the Society of Urologic Oncology (SUO) have released the 2026 amendment to the Advanced Prostate Cancer Guideline, incorporating evidence published from early 2022 through mid-to-late 2025.¹ The update reflects substantial shifts across the disease continuum—from biochemical recurrence after exhaustion of local therapy through metastatic castration-resistant prostate cancer (mCRPC)—with significant new recommendations on treatment intensification, imaging, genetic testing, and bone health. As Kristen R. Scarpato, MD, MPH, who served on the amendment panel, noted, "Even though that's not a huge time period, so much has changed. There was a lot of new information that we incorporated into the guideline."

Two overarching themes define the 2026 amendment: the consolidation of combination therapy as standard of care across nearly all disease states, and an expanded emphasis on molecular and genomic testing to guide individualized treatment. In parallel, the updated guideline reflects a broader role for prostate-specific membrane antigen (PSMA)-PET imaging and emerging theranostic strategies, while continuing to reinforce best practices in bone health surveillance.

The following FAQs highlight key recommendations and practical takeaways for urologists treating patients with advanced prostate cancer.

1. What are the major themes of the 2026 AUA/SUO Advanced Prostate Cancer Guideline amendment?

The amendment is organized around 2 primary themes. The first is treatment intensification. Androgen deprivation therapy (ADT) monotherapy has been largely displaced across disease states by combination regimens incorporating androgen receptor pathway inhibitors (ARPIs), chemotherapy, and, in select patients, radiotherapy. The second theme is the growing role of genomic and molecular testing in guiding treatment selection, including expanded applications for PARP inhibitors in both hormone-sensitive and castration-resistant disease settings.

2. How has the recommended approach to PSMA-PET imaging changed, and how should it influence staging and treatment selection?

PSMA-PET is now preferentially recommended across multiple disease states in the updated guideline, including for patients with biochemical recurrence after exhaustion of local therapy. The guideline cites the superior sensitivity of PSMA-PET compared with conventional imaging for detecting prostate cancer recurrence and metastases at low PSA values (<2.0ng/mL).

However, Scarpato noted that the update does not revise the definition of high-volume vs low-volume disease, which remains based on conventional imaging criteria.

She explained that the expanded use of PSMA-PET raises an unresolved clinical question, noting, "We know that high volume and low volume is really important and can help decide what therapy combination may be best for patients, but the definition that we have historically used and what is carried forth in the guideline is high volume based on conventional imaging. If we're seeing more because the imaging test is better, like PSMA-PET, should we define volume the same? The guideline doesn't really get into that, but I think it's an interesting question, and we'll see more to come on that."

The impact of earlier detection enabled by PSMA-PET on overall survival also remains to be established in prospective data.

3. What does the guideline now recommend for patients with biochemical recurrence after exhaustion of local therapy?

The 2026 amendment introduces a risk-stratified approach supported by level 1 evidence for patients with a rising PSA following exhaustion of local therapy and no demonstrated metastatic disease. Patients are categorized as low-risk (PSA doubling time [PSADT] >9 months) or high-risk (PSADT ≤9 months). Low-risk patients should be offered observation; ADT should not be routinely initiated. High-risk patients should be offered ADT with enzalutamide (Xtandi).

According to Scarpato, this recommendation is grounded in updated data from the EMBARK trial (NCT02319837). The trial randomly assigned patients with high-risk biochemical recurrence to enzalutamide monotherapy, leuprolide monotherapy, or the combination. The most recent publication demonstrated an overall survival advantage for the combination arm.²

Scarpato noted, "There was a pretty impressive overall survival benefit if patients received ADT plus enzalutamide vs ADT alone, or even enzalutamide alone, so the guideline reflects that. It's exciting that we can offer that to our patients, [but] of course [we] have to counsel them about the potential toxicity associated with the systemic therapy combination."

The guideline also notes that intermittent ADT +/- ARPI may be offered in lieu of continuous therapy for high-risk patients who achieve a favorable response.

4. What are the updated recommendations for patients with metastatic hormone-sensitive prostate cancer (mHSPC), and how should clinicians choose among doublet and triplet regimens?

For most patients with mHSPC, clinicians should offer ADT combined with an ARPI (abiraterone acetate [Zytiga] plus prednisone, apalutamide [Erleada], enzalutamide, or darolutamide [Nubeqa]). ADT in combination with docetaxel and either abiraterone plus prednisone or darolutamide is also recommended for select patients. Primary radiotherapy to the prostate in combination with ADT with or without an ARPI may also be offered to select patients.

"The updated guideline acknowledges the level 1 evidence in support of triplet therapy," Scarpato noted, "Importantly, [there are] not a lot of ADT monotherapy recommendations. Certainly, there are exceptions, and sometimes that is the best for a patient, but that's an exception and not a rule."

5. What are the recommendations regarding PARP inhibitors in mHSPC?

In patients with mHSPC with homologous recombination repair (HRR) gene alterations, particularly BRCA2, clinicians may now offer the combination of ADT, abiraterone, and niraparib (Zejula). This is categorized as an Expert Opinion in the guideline.

In the mCRPC setting, PARP inhibitors may be offered to select patients with deleterious germline or somatic HRR mutations who have progressed on prior ARPIs, either as monotherapy or in combination with an ARPI. Platinum-based chemotherapy should be offered to patients who cannot obtain a PARP inhibitor.

6. Who should receive germline and somatic tumor testing, and what is the urologist's role in this process?

The guideline recommends germline testing for all patients with advanced prostate cancer and somatic tumor testing for all patients with metastatic disease. Genetic findings carry both prognostic significance and predictive value, particularly in informing eligibility for PARP inhibitors.

Scarpato emphasized the urologist’s role in this process, saying, "As urologists and the ones who quarterback the care for our patients with prostate cancer, we can tell them this is important because if you have a mutation, it changes what therapies we can offer you. It changes how you may talk to your family members and what tests they may end up getting. We shouldn't be the reason why genetic testing is not offered."

7. What are the updated recommendations for patients with non-metastatic castration-resistant prostate cancer (nmCRPC)?

The guideline continues to recommend apalutamide, darolutamide, or enzalutamide with continued ADT for patients with nmCRPC who are at high risk for developing metastatic disease, defined as PSADT ≤10 months. Observation with continued ADT remains appropriate for lower-risk patients (PSADT >10 months). Systemic chemotherapy and immunotherapy are not recommended outside of a clinical trial in this population.

8. What are the current recommendations for radioligand therapy with lutetium-177 PSMA-617 (¹⁷⁷Lu-PSMA-617; Pluvicto) in mCRPC?

The 2026 guideline reflects an expanded indication for ¹⁷⁷Lu-PSMA-617 in mCRPC based on the PSMAfore trial (NCT04689828).³ Patients with disease progression following an ARPI who have a positive PSMA PET/CT are now candidates for this therapy, without the prior requirement of having failed chemotherapy first.

Scarpato explained, "More recent data showed that patients derived a similar benefit if they had seen ARPIs before, but not chemotherapy. Like many of these therapies for advanced disease, things are moving up sooner."

9. How should clinicians approach bone health monitoring and fracture prevention in patients on long-term ADT?

The guideline recommends that all patients on ADT receive counseling about osteoporosis risk and undergo fracture risk assessment. Preventive strategies include supplemental calcium and vitamin D, weight-bearing exercise, and smoking cessation.

Clinicians should recommend preventive treatments with bisphosphonates or denosumab in patients who have a high fracture risk due to bone loss. For patients with mCRPC and bony metastases, a bone-protective agent (denosumab or zoledronic acid) should be prescribed to prevent skeletal-related events.

Scarpato noted the particular importance of proactive bone management in certain treatment contexts, "We know that [with] some of the therapies that we use, like radium, especially in combination with enzalutamide, we have to preemptively maximize bone health in those patients, because the risk of skeletal-related events is high."

10. What does the guideline say about multidisciplinary care in advanced prostate cancer management?

The guideline reinforces multidisciplinary collaboration as a cornerstone of optimal advanced prostate cancer management. Urologists are positioned as primary navigators of the patient journey, but the complexity of modern treatment regimens requires coordinated input from medical oncology, radiation oncology, genetic counseling, pharmacy, and primary care.

11. What is the broader clinical significance of this guideline update for patients with advanced prostate cancer?

The cumulative impact of the therapies reflected in the 2026 amendment has meaningfully extended survival for patients across the disease spectrum. Historical median survival for mCRPC was less than 2 years; contemporary patients are living substantially longer, with some achieving durable disease control over many years. The guideline's updated recommendations aim to ensure that the full range of evidence-based options is accessible to patients, with treatment decisions personalized to disease characteristics, genomic profile, comorbidities, and patient preference.

12. What emerging therapies or areas of investigation are most likely to shape the field in the coming years?

Although not yet incorporated into formal recommendations, Scarpato acknowledged several evolving areas that warrant close attention. She identified metastasis-directed therapy as a particularly promising area of investigation, citing encouraging phase 2 data and the potential to “help improve quality of life while maintaining a progression-free survival benefit” for selected patients.

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