Overview of Advanced/Metastatic Prostate Cancer

Nilay Gandhi, MD, discusses the rising incidence of advanced/metastatic prostate cancer. Advances in imaging technologies are aiding in early detection and diagnosis, whereas genomic testing is becoming increasingly integral for personalized treatment. Androgen deprivation therapy (ADT) remains the cornerstone for initial treatment of advanced cases, with factors such as patient adherence, cardiac history, and insurance coverage influencing the choice of ADT type. Novel hormonal therapies are being incorporated, especially in castrate-resistant cases, and clinical trials suggest their utility at earlier stages.

NILAY GANDHI, MD: I am Dr Nilay Gandhi with Potomac Urology of Northern Virginia and Maryland, and I’m here to discuss advanced and metastatic prostate cancer.

UROLOGY TIMES®: What is the incidence rate of advanced/metastatic prostate cancer, and how often do you treat patients with advanced prostate cancer in your clinical practice?

NILAY GANDHI, MD: The incidence of advanced and metastatic prostate cancer has been increasing since 2014. A lot of this can be attributed to changes that were seen with the [United States Preventive Services Task Force] guidelines, which declared PSA [prostate-specific antigen] screening grade D, as “not recommended,” back in 2012 and 2013, and subsequently changed it to a grade C recommendation, which is to discuss with your physician. However, due to irregularities with PSA screening within the primary care setting, we are noticing a large amount of increase in advanced and metastatic prostate cancer. That incidence rises by approximately 5% per year, with prostate cancer being the second-leading cause of death in men [in the United States].

The incidence of these patients showing up in a urology clinic is continuing to increase, especially with use of new imaging technologies such as MRIs [magnetic resonance imaging] and PSMA-PET [prostate-specific membrane antigen-positron emission tomography] scans that are becoming more prevalent. We are identifying more patients who are metastatic at diagnosis rather than seeing a trend of patients who become metastatic after primary therapy. One of the key parts that there’s a lot of research going into is determining certain subtypes of patients who have advanced and metastatic prostate cancer. A lot of work has [also] been going into identifying luminal subtypes [and] basal subtypes. That’s an exciting part of the future, [as] identification of these different subtypes will open the door to various different treatment regimens that may be beneficial for patients. So, we are really moving away from a very broad prostate cancer treatment for all patients and [are] able to now identify specific markers within each patient’s individualized cancer, [which] allows for personalized medicine.

UROLOGY TIMES: How is advanced/metastatic prostate cancer diagnosed? What clinical workup is required, and what are the prognoses for these patients?

NILAY GANDHI, MD: In today’s age, there is a greater utilization of prostate MRI, which has allowed for incorporation of targeted and fusion prostate biopsy into our practices. Additionally, the incorporation of PSMA-PET scans over the past few years has really allowed for the detection of micrometastatic disease in high-risk men, so we are detecting metastatic disease earlier due to the use of PSMA-PET scans. But with the utility of MRIs, PSA-PET scans, and—in some instances —utilization of [computerized tomography] scans or nuclear medicine bone scans, we [can] identify and diagnose men with advanced or metastatic disease. It is also currently becoming a mainstay in practice to incorporate genomic [and] genetic testing. That is where we see a lot of the future of advanced and metastatic prostate cancer heading because these have now been incorporated into the [National Comprehensive Cancer Network] guidelines but really allows for more personalized medicine [as] we’re able to identify specific mutations or genomic markers, [which] allows for specific treatment options for patients or identification [regardless of] what their responsiveness will be to androgen deprivation therapy [ADT] or other medications that may be available. The prognosis for men with advanced or metastatic prostate cancer has greatly changed over the past 10 years, and this has been due to the amount of research, identification, and creation of novel therapeutic agents that now allow us to treat men in the metastatic setting. [We’re] now seeing a shift toward treating these men who are high risk in the nonmetastatic setting, with the goal to prevent further metastasis.

UROLOGY TIMES: What is the goal of [ADT], and what is the rationale for use in metastatic hormone-sensitive prostate cancer?

NILAY GANDHI, MD: [Although] ADT has always been the mainstay for patients with high-risk and advanced prostate cancer, the concept behind this involves depriving the prostate cancer cells of testosterone, therefore causing apoptosis and regression of cancer. So, ADT typically is always the mainstay for any patient [who] is high risk or becomes advanced and metastatic as an initial treatment prior to the initiation of additional therapeutic agents. [ADT] is utilized in the metastatic space, and you want to ensure you’re checking your patient’s testosterone levels to determine [whether] they are castrate sensitive or castrate resistant. There have been numerous studies looking at community urology practices and incorporation of testosterone blood work with [ADT], and most people test only for PSA. However, the importance of checking testosterone levels to ensure whether a patient is castrate is also part of the next treatment algorithm because some medications are allowed only in a castrate-resistant space. So please make sure you’re checking testosterone levels in addition to PSA while incorporating ADT into the advanced workup.

UROLOGY TIMES: What are the different types of [ADT]? How do you select the best treatment among those different ADT options?

NILAY GANDHI, MD: There are many different types of [ADT] options available. Most are aware of [luteinizing hormone-releasing hormone] agonists [and] antagonists, and there are many different options that are currently available on the market for utilization within practice. When determining which ADT is most suitable for your patient, there are multiple factors to consider, and some of these factors can depend on a patient’s [adherence]. It can depend on their cardiac history, the duration that they will be on [ADT], their insurance coverage, [and] potential out-of-pocket costs or patient preferences. As we’ve learned with anything regarding prostate cancer, as well as prostate cancer screening, informed decision-making is essential. Having these conversations with the patients about what these different treatment options are, how they can impact their overall care in terms of potential testosterone flare, as well as testosterone recovery after treatment are very important—as much as the financial burden that may impair the patient as well.

[ADT] can also contribute some challenges to the patients, and this typically is in the form of [adverse] effects [AEs], such as hot flashes, fatigue, [and] changes in their sexual function. These are definitely conversations to have with the patients, [as] this can also lead to discontinuation of ADT from the patient perspective if [AEs] become unmanageable or intolerable. Additionally, you want to assess patients for their blood glucose levels as this can cause an increase, especially in men [who are diabetic].

UROLOGY TIMES: When might you consider adding on novel hormonal therapy to [ADT]?

NILAY GANDHI, MD: In recent years, there has been the initiation of additional medications incorporated with [ADT] that can help assist men with advanced prostate cancer. These have been the oral oncolytic medications that we’ve incorporated with [ADT]. These patients have typically been castrate resistant and metastatic prior to the initiation of these novel hormonal therapeutic agents. However, there has been recent data that we see in clinical trials—with the STAMPEDE [and] EMBARK clinical trials [NCT00268476, NCT02319837]—that will allow for the initiation of these medications at an earlier stage. We are starting to see incorporation of these medications in the high-risk nonmetastatic setting, which would hopefully allow for the prevention of these patients progressing to metastasis.

UROLOGY TIMES: What are some unmet needs in the treatment and management of advanced prostate cancer?

NILAY GANDHI, MD: Advanced prostate cancer management has continually been evolving and has undergone significant changes over the past 10 years. There are still certain significant barriers and unmet needs that are occurring for our patients and our community practices. I believe a lot of this centers around education for providers regarding these ever-changing guidelines. With advanced prostate cancer and the initiation of new medications and incorporation of genetic and genomic testing, a lot of the barriers we face revolve around access to care, insurance coverage, [and] out-of-pocket costs to the patient. So as we continue to navigate the advanced prostate cancer space, these are some barriers that we will have to encounter to help provide the best level of care for our patients.