The challenges of prostate cancer management

Raoul S. Concepcion, MD, FACS

Historically, the urology community has been the “gatekeeper” for the diagnosis and management of prostate disorders, malignant or benign. Prior to the advent of medical therapy and minimally invasive procedures to treat benign prostatic hyperplasia (BPH), if one were finishing their training and in search of a job opportunity, the litmus test to determine how busy a urologist was in practice was to ask how many transurethral resections of the prostate (TURPs) were being performed annually? If the number was more than 125 cases per year, that was considered a robust clinical practice. My recollection from my case log as a resident in the late 1980s was maybe 100 cases over a 4-year residency span, and I cannot fathom what that might look like today in the modern era! The transition from open prostatectomy, TURP, medical therapy, and now minimally invasive procedures has required, to some degree, subspecialization to optimize outcomes rather than being the staple procedure for all urologists in practice.

The evolution in the diagnosis and management of prostate cancer has been equally complex. Akin to BPH, the various facets of the disease require the urologist in practice to stay abreast of the many advances and breakthroughs that are constantly being developed in order to stay current and provide state-of-the-art care. To that end—especially in larger independent practices, and certainly in academic centers—we have specialization in certain clinical areas within prostate cancer itself.

Diagnosis of prostate cancer

The early detection of prostate cancer remains critical and should always be in the hands of urology to educate the broader medical community. Mistakenly, we have applied the term screening to the various tests deployed. In its purest form, a screening test is used to aid in the detection of a certain disease in an asymptomatic population. A positive test suggests the high likelihood of that condition being present, and a negative test would indicate the absence of disease.¹ Prostate-specific antigen (PSA) is not a good test for screening, but if it is used judiciously, it is still the linchpin in early detection of prostate cancer. Despite the controversial and subsequent reversal of the US Preventive Services Task Force (USPSTF) recommendations,² most PSA testing is still carried out by primary care physicians in the United States.³ It is our role, as the subject matter experts, to educate our primary care colleagues on the limitations of PSA testing, as well as the following:

• The goal of early detection is to identify those patients at risk for significant prostate cancer.
• Current adjuvant testing to PSA, whether that be imaging or liquid-based testing.
• Current advances in biopsy technique.

Localized prostate cancer

For decades, we have understood that if a man lives into his eighth or ninth decade of life, there is a strong likelihood that he will develop histologic prostate cancer, but not necessarily die of this disease. Most of these individuals will have a lower Gleason Score and Grade Group disease, vis à vis, pattern 3 microscopically. Semantically, as we discuss prostate cancer with newly diagnosed patients or colleagues, it is important for us to be more specific and base these conversations relative to risk stratification.⁴ Due to the aforementioned USPSTF recommendation and the lay press, many of our patients—and referring primary care physicians—believe that prostate cancer does not need to be treated. We need to emphasize:

1. Active surveillance for low-risk disease is appropriate for initial therapy but does not mean that treatment will never be indicated.
2. The role of active treatment, either surgical or radiation, is still indicated in select risk groups.
3. Systemic therapies may also play a role in those with high-risk disease, especially in light of advanced molecular imaging.

Advanced prostate cancer

The major shift for many urologists over the past 10 years has undoubtedly been the understanding of how to treat advanced prostate cancer. Here, and in the countless number of publications currently available, the message has been the role of urologists to embrace the management of these patients. The complex nature of the disease, and the multiple agents and regimens now FDA approved for these patients, has led to specific providers within a practice being charged to oversee programs distinct from those managing localized prostate cancer. If we designate an arbitrary definition of “advanced” as any patient that requires androgen deprivation therapy (ADT) for suspected progression of disease, it is critical to acknowledge:

1. Not all patients with biochemical relapse who have been definitively treated for prostate cancer require ADT.
2. If ADT is required, urologists need to take inventory of preexisting cardiovascular risks, given the increasing data suggesting major adverse cardiovascular events associated with certain agents.
3. The standard of care for any patient with newly diagnosed metastatic prostate cancer is the initiation of ADT plus extended therapy, whether that be androgen receptor targeting agents or taxane-based chemotherapy.
4. The plethora of agents currently available for the patient with metastatic castration-resistant prostate cancer continues to expand, including many trials investigating unique combinations of drugs that are approved as monotherapy.

What’s on the horizon?

Advanced molecular imaging. The current and forthcoming approvals of various prostate-specific membrane antigen (PSMA) scans will markedly change the therapeutic landscape of the disease, especially as the approval may allow use in staging for high-risk/high-grade prostate cancer.

Theranostics. Close on the heels of PSMA approval is radioligand therapy, which is already approved overseas, and is soon to be approved in the US. Yet another agent in our armamentarium.

Genomic testing. Probably the hottest and least understood area, the incorporation of germline and somatic testing to manage and define risk will be standard of care. However, incorporating this into our practice models remains a challenge, but not an excuse to ignore at the present.

Support clinical trials. The number of unique agents and regimens (bispecific T-cell engager, bipolar androgen therapy, androgen receptor transport disruptors/degraders, etc) continue to be investigated, with promising results early on. As our understanding of molecular drivers and resistance continues to increase through genomic testing, the promise of precision medicine may soon become reality.

References

1. Maxim LD, Niebo R, Utell MJ. Screening tests: a review with examples. Inhal Toxicol. 2014;26(13):811-828. Published correction appears in Inhal Toxicol. 2019;31(7):298. doi:10.3109/08958378.2014.955932

2. United States Preventive Services Task Force. Final recommendation statement – prostate cancer: screening. May 8, 2018. Accessed August 23, 2021. https://bit.ly/3mHAXnB

3. Rim SH, Hall IJ, Richards TB, et al. US primary care physicians’ prostate cancer screening practices: a vignette-based analysis of screening men at high risk. Health Serv Res Manag Epidemiol. 2014;1:2333392814562909. doi:10.1177/2333392814562909

4. NCCN. Clinical Practice Guidelines in Oncology. Prostate cancer, version 2.2021. Accessed August 23, 2021. https://bit.ly/3kndzsn