Prostate Cancer and Prostatic Diseases

The majority of urologists performing radical prostatectomy in developed populations are doing so with robotic platforms. Since adopting this approach, many of us have observed that our patients appear to have less pain and recover more rapidly. If we are brutally honest with ourselves, we have all probably lowered our bar for accepting patients for surgery on the basis of overall health because they seem to handle robotic-assisted surgery better than open surgery. In my own practice, for patients not willing to consider radiotherapy and were frail by my own subjective assessment, I would routinely send these patients for a review by one of my internal medicine colleagues who is by training a geriatrician and has developed a special interest in perioperative medicine. Almost always, these patients were then being cleared for surgery and gradually I have found that I am operating on more of these types of patients apart from just older patients.

Urethral wall stents were introduced as a minimally invasive intervention for benign prostatic hyperplasia (BPH) in the 1990s. Despite reports of longer-term efficacy in select patients,^1,2 challenges with recurrent occlusion and stent migration^3-5 prevented widespread adoption of this technology.

Over the past 10 years, however, novel designs and new materials have sparked renewed interest in developing the next generation of urethral stents.⁶ These investigators reported updated data on a single-arm study of 81 patients with symptomatic bladder outlet obstruction who received a temporary implantable nitinol device.⁷ The device—composed of three nitinol struts and an anti-migration anchoring leaflet—remained in place for 5 to 7 days, expanding and exerting radial force on the tissue to cause ischemic incisions at the 12, 5, and 7 o’clock positions. Implantation occurred under direct vision through a rigid 19F-22F cystoscope using light intravenous sedation, and removal through an open-ended 22F Foley catheter with topical anesthesia.

Treatments for prostate cancer have rapidly evolved over the past nearly 10 years. Prior to this, the only approved life-prolonging agent for advanced prostate cancer was docetaxel. However, that all changed with the approval of abiraterone and enzalutamide. Both drugs showed profound benefits for men with metastatic castration-resistant prostate cancer (mCRPC). For these men, survival was measured in months and thus, the long-term toxicity of any therapies was not relevant. Acute toxicities were generally mild and manageable. As such, these agents made a huge impact and became widely used.

Newer data suggest that both abiraterone and enzalutamide also improve survival when given to men with metastatic castration-sensitive prostate cancer (mCSPC). For these men, survival is not measured in months, but rather years. As such, long-term toxicities become more relevant and are of keen interest.

We are seeing an increasing number of studies evaluating the role of fluorinated ligands for prostate-specific membrane antigen (PSMA) PET/CT. Data to this point in time has not shown any convincing diagnostic advantage or disadvantage with the use of either fluorine F 18 (F18 DCFPyL) and gallium (Ga) Ga68 HBEDD-11 PSMA PET/CT tracers although the former has obvious logistical benefits in busy nuclear medicine departments. This study by Witkowska-Patena and colleagues is amongst the first studies to look at a relatively new fluorinated tracer in the form of F18 PSMA-1007. This tracer is already becoming commercially readily available and well before we have good data on its utility and capability.

The justification for yet another PSMA tracer appears to be sound although this is not specifically discussed in the paper. The potential advantage of F18 PSMA-1007 is that there is significantly lower urinary excretion of the tracer; as a result, there is the minimization of tracer within the urine that could potentially impact the interpretation of tracer uptake in areas adjacent to the urinary tract.

In the constant search for better approaches to treat and ultimately prevent prostate cancer, it is essential that we better understand the underlying etiology of prostate cancer. In times like this, I am often discouraged by the common mantra that the only known risk factors for prostate cancer are “age, race, and family history”. Surely, there must be other risk factors. Over time, certain risk factors have revealed themselves – obesity (aggressive prostate cancer), diet (likely, but exact details still evolving), and smoking (aggressive prostate cancer) to mention a few. One common factor, but certainly not the only factor, linking obesity, diet, and smoking is they all increase inflammation. If true that increased inflammation drives more prostate cancer, then it begs the question of whether other conditions that are clearly inflammatory-related are linked with prostate cancer. With this background in mind, Ge and colleagues tested the association between inflammatory bowel disease (IBD) and prostate cancer risk.

Active surveillance (AS) is an alternative to definitive therapy for patients with the National Comprehensive Cancer Network very low-risk, low-risk, and favorable intermediate-risk prostate cancer.¹ However, 20% to 30% of AS patients will grade progress on follow-up biopsy or undergo treatment within five years.^2-5 Prevention of grade progression in AS patients would decrease treatment incidence, reduce costs of care, and improve health-related quality of life in men on active surveillance.

5-alpha-reductase inhibitor (5ARI) therapy is one potential intervention to prevent progression in AS patients. Robust data demonstrate that 5ARIs diminish grade progression and the use of definitive treatment in AS patients.⁶ Nevertheless, the U.S. Food and Drug Administration black box label warning of possible risks of the incident high-grade disease remains, and the use of 5ARIs in men on AS to prevent progression has not been widely embraced. 

Black men face a pandemic of prostate cancer risk and lethality which will still be present long after COVID passes. As compared to White men, Black American men have a high risk of presenting with aggressive and metastatic disease and suffer a 2.4 fold higher risk of prostate cancer-specific mortality, and a nearly 10-fold higher risk of death from prostate cancer as compared to Asian American men. This disparity in outcomes is present in both rural and urban regions¹ in the United States and some of the highest global regions of prostate cancer mortality are in Africa and the Caribbean. This racial disparity may be linked to differences in biology^2,3, access to care⁴, differences in treatment receipt, comorbidities, differences in risks and exposures, and differences in screening and early detection. 

In light of this observed disparity, Krimphove and colleagues⁵ from Harvard analyzed the National Cancer Database for all men with metastatic or locally advanced prostate cancer between 2004-10 and compared outcomes by race. Overall, Black men were more likely to have metastatic disease in this cohort as compared to locally advanced disease, were less likely to receive surgery or radiation, were more likely to be uninsured, were more likely to be treated locally, and to have not completed a high school education.