The American Urological Association (AUA) and the Society of Urologic Oncology (SUO) have released a 2023 update to their clinical practice guideline on advanced prostate cancer, first published in 2020.

A panel reviewed 16 studies published from 2018 through March 16, 2022, and updated evidence- and consensus-based statements. The amendment includes updates to recommendations for biochemical recurrence, metastatic hormone-sensitive prostate cancer (mHSPC), nonmetastatic castration-resistant prostate cancer (nmCRPC), and metastatic castration-resistant prostate cancer (mCRPC).

“While metastatic prostate cancer remains a lethal disease, improvements in overall survival (OS) through combination therapies have resulted in a renaissance in the entire landscape for clinicians caring for men with advanced metastatic prostate cancer,” William Lowrance, MD, of Bon Secours Mercy Health in Greenville, South Carolina, and colleagues wrote in The Journal of Urology.

Biochemical Recurrence

In patients with biochemical recurrence and a PSA doubling time less than 12 months, the preferred imaging modality for periodic staging is now prostate-specific membrane antigen (PSMA) positron emission tomography (PET) imaging, although computed tomography (CT), magnetic resonance imaging (MRI) and technetium bone scan are still permitted. PSMA-PET also is recommended when conventional imaging is negative. PSMA-PET agents that are approved by the US Food and Drug Administration (FDA) for advanced prostate cancer include ⁶⁸Ga-PSMA-11 and Piflufolastat F-18 (18F-DCFPyL).

In the absence of radiographic metastases, clinicians and patients can choose observation or a clinical trial. There currently is no evidence on the best time to start androgen deprivation therapy (ADT). Dr Lowrance and colleagues noted that ADT is sometimes given when PSA is rising rapidly without radiographic evidence. Earlier recurrences after local therapy may indicate more aggressive disease.

Metastatic Hormone-Sensitive Prostate Cancer

Clinicians should assess the extent of lymph node, bone, and visceral metastases in patients newly diagnosed with mHSPC. The guideline update acknowledges the availability of non-conventional imaging modalities to locate metastatic sites and assess metastatic volume.

“Utilization of PSMA-PET may lead to the diagnosis of metastatic disease not previously detected with conventional imaging,” Dr Lowrance and colleagues pointed out.

Germline testing is underused in metastatic prostate cancer and is now strongly recommended. Clinicians should also consider somatic testing and genetic counseling. Dr Lowrance and colleagues highlighted that genetic counselors are equipped to explain results and their implications to patients and their families, who may benefit from testing if a mutation is found.

To prolong survival with mHSPC, intensified therapy is recommended, including ADT in combination with either androgen pathway-directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel). Docetaxel carries significant toxicity, especially in older patients, that should be discussed, according to Dr Lowrance and colleagues. They also noted the seizure risk associated with some androgen pathway-directed therapies.

De novo mHSPC may have worse biology. The guideline recommends that clinicians offer intensified therapy, including ADT, in combination with docetaxel and either abiraterone acetate plus prednisone or darolutamide in selected patients. (Editor’s note: Newly release results from the PEACE-1 trial show radiation plus intensified systemic therapy is beneficial in low-volume de novo mHSPC.)

Nonmetastatic Castration-Resistant Prostate Cancer

Every 6 to 12 months, clinicians should look for metastatic disease using PSMA-PET or conventional imaging in patients with nonmetastatic CRPC, according to the guideline. The interval is determined by the PSA doubling time and symptoms, with an interval of 10 months or less associated with a high risk of metastases or death.

Yearly imaging is recommended for patients taking androgen receptor pathway inhibitors.

Metastatic Castration-Resistant Prostate Cancer

In patients with mCRPC without PSA progression or new symptoms, perform imaging at least annually, the guideline authors advise. Such routine imaging can identify patients with radiographic progression without PSA progression, Dr Lowrance and colleagues explained.

The authors advise ordering PSMA-PET imaging before considering 177lutetium (¹⁷⁷Lu-PSMA-617) in patients with mCRPC who have PSA or radiographic progression or new symptoms following treatment with docetaxel and an androgen pathway inhibitor. If PSMA-PET is positive, ¹⁷⁷Lu-PSMA-617 should be offered.

Toward personalized therapy, the guideline advises germline and somatic testing to identify DNA repair deficiency, microsatellite instability (MSI) status, tumor mutational burden, and other potential mutations that may inform prognosis and familial cancer risk and help guide use of certain therapies, such as PARP inhibitors or immunotherapy.

The guideline amendment also recommends that patients newly diagnosed with mCRPC who have not received prior androgen receptor pathway inhibitors should be offered continued ADT with abiraterone acetate plus prednisone, docetaxel, or enzalutamide.

Unmet Needs and Future Directions

Optimal sequencing of advanced prostate cancer therapies and optimal treatment intensification and combinations of therapy have yet to be determined, Dr Lowrance and colleagues revealed. Personalized care based on tumor and patient biology has not been fully realized. What is clear is integrated multidisciplinary care is increasingly important for prostate cancer management.

Researchers are investigating earlier use of ¹⁷⁷Lu-PSMA-617 for CRPC as well as mHSPC, biochemically recurrent disease, and even high-risk localized disease as neoadjuvant therapy, the authors noted. Researchers are also examining the theranostic’s durability.

PSMA-PET imaging has renewed interest in metastasis-directed therapy using radiation, surgery, or ablation, the authors reported. Treating high-risk prostate cancer with neoadjuvant therapies prior to surgery is another area of interest.

The authors also acknowledged that reducing disparities in advanced prostate cancer care for Black patients and improving access to care for socioeconomically disadvantaged patients are key goals.

Reference

Lowrance W, Dreicer R, Jarrard DF, et al. Updates to advanced prostate cancer: AUA/SUO Guideline (2023). J Urol. 209(6):1082-1090. doi:10.1097/JU.0000000000003452