Bilal A. Siddiqui, MD, assistant professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the nuances of defining the characteristics of nonmetastatic castration-resistant prostate cancer (CRPC). 

One nuance is the castrate level of testosterone, which has a widely accepted definition of having a serum testosterone of less than 50 ng/dL, according to Siddiqui. In addition, the rise of prostate-specific antigen (PSA), despite castrate testosterone, has some differences in definition, Siddiqui adds. However, the most common use of PSA rise is defined by the Prostate Cancer Working Group 3 as a confirmed 25% increase from a nadir of 1, Siddiqui says.

Moreover, these patients have no evidence of distant metastatic disease beyond the regional lymph nodes by conventional imaging per computed tomography scans, magnetic resonance imaging, and technetium bone scan, Siddiqui explains. These nuances are important for imaging and treatment, and they will continue to change over time with the emergence of novel imaging technologies, Siddiqui adds. These are the key definitions to keep in mind for the time being, Siddiqui concludes.

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Bilal A. Siddiqui, MD, discusses the nuances of defining the characteristics of nonmetastatic castration-resistant prostate cancer.

Dr. Siddiqui on Defining Characteristics of Nonmetastatic CRPC 

Bilal A. Siddiqui, MD, assistant professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses selecting between available antiandrogen agents in nonmetastatic castration-resistant prostate cancer (CRPC).

Currently, the antiandrogen agents enzalutamide (Xtandi), apalutamide (Erleada), and darolutamide (Nubeqa) are FDA approved for use in men with nonmetastatic CRPC, Siddiqui says. The regulatory decisions were based on findings from 3 randomized trials that each enrolled over 1000 patients with nonmetastatic CRPC who had a prostate-specific antigen doubling time of 10 months or less and no evidence of distant metastatic disease by conventional imaging. The primary end point of the studies was metastasis-free survival (MFS).

The results of the studies demonstrated similar MFS and overall survival improvements across the 3 agents compared with placebo, Siddiqui explains. As such, treatment selection should be informed by the individual safety profiles of enzalutamide, apalutamide, and darolutamide.

Patients with a history of seizures are not suited for darolutamide as it has demonstrated lower blood-brain barrier penetrance compared with enzalutamide and apalutamide. Other considerations to inform selection include the risk of rash, which is greatest with apalutamide, drug-drug interactions, patient comorbidities, and cost, Siddiqui concludes. 

Bilal A. Siddiqui, MD, discusses selecting between available antiandrogen agents in nonmetastatic castration-resistant prostate cancer.



Dr. Siddiqui on Selecting Between Antiandrogen Agents in Nonmetastatic CRPC 

Bilal A. Siddiqui, MD, assistant professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the potential for novel imaging in patients with nonmetastatic castration-resistant prostate cancer (CRPC). 

A recent study enrolled 200 patients with nonmetastatic CRPC who had a prostate-specific antigen level that was greater than 2, a doubling time of about 10 months, and no evidence of distant metastatic disease based on conventional imaging, according to Siddiqui. When investigators applied prostate-specific membrane antigen imaging, as well as positron emission tomography and computed tomography scans, however, lesions were detected in 98% of patients. Approximately half of the patients had distant metastatic disease, Siddiqui adds.

The additional imaging altered the way these patients would be treated, based on their updated disease state, Siddiqui says. As more is learned about how best to leverage imaging technologies, a big shift will be seen in the treatment of patients with nonmetastatic CRPC, Siddiqui concludes.

Bilal A. Siddiqui, MD, discusses the potential for novel imaging in patients with nonmetastatic castration-resistant prostate cancer.

Dr. Siddiqui on the Potential for Novel Imaging Techniques in Nonmetastatic CRPC 

Bilal A. Siddiqui, MD, assistant professor, Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the current state of treatment in nonmetastatic castration-resistant prostate cancer (CRPC). 

Nonmetastatic CRPC is defined by a castrate level of serum testosterone less than 50 ng/dL, rising prostate-specific antigen despite the use of androgen-deprivation therapy, and no evidence of distant metastatic disease by conventional imaging, Siddiqui says.

Currently, the antiandrogen agents darolutamide (Nubeqa), enzalutamide (Xtandi), and apalutamide (Erleada) are FDA approved for use in patients with nonmetastatic CRPC, Siddiqui says. Although cross-trial comparisons are flawed, the agents have demonstrated similar metastasis-free survival and overall survival in patients with nonmetastatic disease. Therefore, factors regarding each agent’s safety profile, drug-drug interactions, and cost need to be considered when selecting between the 3 available agents. 

Additionally, as next-generation imaging with PSMA PET CT scans emerge, which have increased sensitivity for distant metastatic disease detection, it is possible that nonmetastatic CRPC will not be a disease state in the next decade, Siddiqui concludes.

Bilal A. Siddiqui, MD, discusses the current state of treatment in nonmetastatic castration-resistant prostate cancer.



Bilal A. Siddiqui, MD

Articles

Dr. Siddiqui on Defining Characteristics of Nonmetastatic CRPC

Dr. Siddiqui on Selecting Between Antiandrogen Agents in Nonmetastatic CRPC

Dr. Siddiqui on the Potential for Novel Imaging Techniques in Nonmetastatic CRPC

Dr. Siddiqui on the Current State of Treatment in Nonmetastatic CRPC