Prostate Cancer and Prostatic Diseases: From the Editor
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Role of Physical Activity and Its Link with Lower Rates of Progression in Men on Active Surveillance - Editorial
In this study, the authors assessed 85 men with low-risk prostate cancer being managed by active surveillance. All men completed a physical activity questionnaire at baseline and were categorized as sedentary (n=24), moderately active (n=46), or active (n=15). The authors then assessed the risk of grade reclassification, commonly used criteria for “progression” among men on active surveillance. The authors found that those who progressed were less physically active (p=0.056). Importantly, over time, the level of physical activity was significantly predictive of who progressed (p=0.033). Indeed, on multivariable analysis, the level of physical activity was the only significant predictor of progression (p=0.016). The authors concluded that physical activity may influence prostate cancer evolution.
PSA Response to Antiandrogen Withdrawal To Identify the Response on Type of Antiandrogens - Editorial
In 2021-2022, many more men globally will receive a potent AR inhibitor in either the metastatic hormone sensitive prostate cancer (mHSPC), non-metastatic castration resistant prostate cancer (nmCRPC), or mCRPC settings, with improved long term outcomes based on multiple positive phase 3 trials of abiraterone, enzalutamide, apalutamide, and darolutamide. This new form of maximal or combined androgen blockade in addition to ADT has extended survival, delaying symptomatic and metastatic progression, improving durable remissions based on PSA and imaging response criteria, major successes for our patients.
With first generation AR inhibitors such as flutamide and bicalutamide, prolonged responses to these therapies often led to anti-androgen withdrawal responses which were observed at progression after the patient stopped these agents. These withdrawal responses were due to point mutations in the ligand binding domains of the AR (such as T877A), turning these older agents into agonists that stimulated AR activity and PSA production. Withdrawal responses typically would last 3-6 months, but occasionally patients would experience prolonged withdrawal responses lasting over a year. However, the prevalence of withdrawal responses to stopping these novel AR inhibitors has not been well described.
Real-World Clinical Utility of Decipher Biopsy Testing in Localized Prostate Cancer
A commercially available test is Decipher Biopsy. The potential of this test on post-radical prostatectomy decision-making is well documented. This is also shown for other molecular gene expression-based classifiers. This paper describes the outcome of a state-wide registry of patients in AS. The test is significantly associated with time to treatment and time to failure. The paper shows that the Decipher score correlates with Grade Group, NCCN- and CAPRA risk scores.
MRI Prior to Prostate Biopsy Is Best Evidence Practice and a Standard of Care
As a randomised controlled trial, the PRECISION study1 showed a clear benefit of an MRI pathway in terms of improved detected of clinically significant prostate cancers and decreased detection of clinically insignificant prostate cancers. However, it seems that not all urologists are convinced by the data or sufficiently motivated to change clinical practice on the strength of this study. That said, it is accepted that access to prostate MRI due to reimbursement issues could play a role in some jurisdictions.
The 2021 EAU Guidelines2 have clearly spelt out a recommendation that an MRI should be performed prior to prostate biopsy whether it be those men who are biopsy naïve or have previously had a negative prostate biopsy. The strength rating for both recommendations is “strong”. The 2021 NCCN Guidelines3 are a little more guarded in that the recommendation for an MRI prior to prostate biopsy is qualified by the words ‘if available’. Particularly in the US, 3T MRI is widely available but sadly, it is an issue of reimbursement despite the highest level of evidence to support its routine use prior to prostate biopsy.
The Resistance Training Effects in Prostate Cancer Patients, Determining the Minimal Dosage – Editorial
Doctor: “You have prostate cancer.”
Patient: “Doctor, that’s awful. What can I do to help it grow slower and feel better?”
Doctor: “Eat right and exercise.”
Patients: “How much exercise should I do?”
Doctor: “I don’t know.”
While the above is a fictitious discussion between doctor and patient, my guess is that similar discussions occur every day. When diagnosed with cancer, patients want to improve their lifestyle and clamor for any information their provider can give them. Unfortunately, most providers don’t know what advice to give. Even if the provider is knowledgeable and interested, discerning the literature and coming up with an answer to a straightforward question such as “how much exercise” is not an easy task. Into this void, steps the systematic review and meta-analysis by Lopez and colleagues.
The Importance of Bone Health Management in Men with mCRPC - Editorial
It is well appreciated that men with bone metastases are at risk for fracture and symptomatic skeletal-related events (SREs), and that men on long-term potent hormonal therapies are at risk for fragility fractures due to ongoing bone loss. However, the utilization of denosumab and zoledronic acid, despite the widespread guideline recommendations for their consideration, remains low internationally. This was recently highlighted at ASCO 2021 with the PEACE3 clinical trial, where the mandated use of bone antiresorptive therapy in this bone mCRPC protocol of enzalutamide +/- radium-223 led to an improvement in the use of these agents in this population from 55% to 97%, and reduced the observed fracture rate at 18 months with enzalutamide alone from 22% to 2.6%, a major reduction in risk.1
Novel Prostate Cancer Susceptibility Gene SP6 Predisposes Patients to Aggressive Disease - Editorial
In this study based on a ‘’narrow/isolated’’ Finnish cohort, 21 low penetrance susceptibility loci were identified, of which 10 are novel. The intronic variant rs2074187 in SP6 was associated not only with overall susceptibility to PrCa (OR 1.66) but also with a higher odds ratio for aggressive PrCa (OR 1.89) and lower odds for non-aggressive PrCa (OR 1.43). Furthermore, the new intergenic variant rs79012498 at 8q24 conferred risk for aggressive PrCa. These are important as they are associated with significant prostate cancer. Such variants may be useful in the stratification of patients for population based screening.
Overall Survival of Black and White Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC): A 20-Year Retrospective Analysis in the Largest Healthcare Trust in England - Editorial
Differences in the Use of Fusion Biopsy Between Black and White Men Presenting with Suspicion of Prostate Cancer - Editorial
For decades, clinicians and researchers alike have been aware of major racial disparities in prostate cancer. Black men in the United States present more often, with higher PSA values, at younger ages, and are more likely to die from prostate cancer than their White counterparts. Within this framework of indisputable facts, there is a lot of discussion to what factors lead to these racial disparities. Is it genetics? Is it social determinants of health? Is it attitudes to the health system due to mistrust from many past horrible failed experiments (i.e. Tuskegee)?
Is it lifestyle differences? Is it all access to care? Recent data from the Veterans Affairs Health System have suggested that when given equal access, outcomes among Black and White men can be similar. While this certainly supports the importance of access to care, this does not mean Black and White men present with equal rates of prostate cancer indicating residual disparities that cannot be explained by access alone. However, as we move forward with newer technologies (MRI, genomics, next generation imaging), whether Black patients truly have equal access to these advances is unknown.
The Role of Androgen Receptor (AR) in Liquid Biopsy to Predict Clinical Outcome to AR Signaling Inhibitors in Metastatic Castration Resistance Prostate Cancer Patients - Editorial
Recommendation for the Use of Genomic Classifiers in Determining Patient Eligibility for Adjuvant Radiation Therapy - Editorial
A genomic classifier (GC) with prognostic indication, Decipher (Decipher Biosciences), aids in the decision for adjuvant radiotherapy (ART). In this study, the authors show that whereas the decision would have been "observation" in 39% of pre-genomic testing cases, the recommendation changed. The authors conclude that the use of GC substantially altered treatment decision-making, with a number needed to test of only 3.
Adverse Short-Term Postoperative Outcomes in Patients Treated with Radical Prostatectomy Predicted by Preoperative Frailty - Editorial
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.
Temporary Implantable Nitinol Device (iTIND) Demonstrates Reduction In Symptoms and Improved Qol For Men Suffering From Lower Urinary Tract Symptoms Secondary to Benign Prostatic Obstruction - Editorial
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 migration3-5 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.
Adverse Effects on the Cardiovascular System in Men with Metastatic Castration-Resistant Prostate Cancer (mCRPC) Treated with Abiraterone or Enzalutamide - Editorial
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.
How Do You Define Androgen Receptor Indifferent Prostate Cancer? - Editorial
18F-PSMA-1007 PET/CT for Diagnosis and Detection of Biochemically Recurrent Prostate Cancer - Editorial
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.
The Risks of Biochemical Recurrence and Death in Men Receiving Testosterone Therapy After Treatment for Localized Prostate Cancer - Editorial
Sarkar and colleagues study the effect of testosterone therapy (TT) in men that were treated with curative intent (radiation therapy or surgery). From a significant cohort(~70,000 men) a group of men undergoing TT was compared to those who did not, and biochemical recurrence was used as an endpoint. The authors recognize the limitation that this an observational type of study, as time on testosterone, and serum testosterone values were not available.
Inflammatory Bowel Disease and Prostate Cancer Risk— Editorial
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.
The Efficacy and Safety of Long-term Use of 5-alpha-reductase Inhibitors for Preventing Progression in Prostate Cancer Patients on Active Surveillance – Editorial
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.
Initiatives to Improve Access to Care and their Effect on Reducing Racial Disparities in Prostate Cancer Outcomes - Editorial
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 biology2,3, 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.
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