Prostate Cancer and Prostatic Diseases: From the Editor
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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.
Can We Better Define the Patients that Benefit from Sipuleucel-T Treatment? - Editorial
Overcoming Barriers to Performing Transperineal Prostate Biopsies - Editorial
Much of the push to perform transperineal prostate biopsy has been driven by concerns about increasing rates of sepsis associated with the transrectal approach to needle biopsy.
Historically, the strategy to minimize the infective complications of prostate biopsy had relied upon using more and more potent antibiotic regimens to combat growing bacterial resistance. A more recent approach to mitigate the risk of sepsis has been to use the more potent antibiotics in a targeted manner guided by rectal swabs prior to biopsy. However, the concept of chasing increasing antibiotic resistance with increasingly powerful antibiotics is a strategy that will never win.
The transperineal approach to prostate needle biopsy is a logical way forward given that the risk of biopsy sepsis is minimal. It should be the standard of care approach to prostate biopsy but there is a reluctance to change practice and much of this is based upon the arguments that expensive equipment is necessary and that a general anesthetic is necessary. Recent advances are seeing these issues overcome.
Prolonging Overall Survival in Men with mCRPC with New Systemic Therapies - Commentary
In the past 10 years, the number of new treatment options for metastatic castration-resistant prostate cancer (mCRPC) has exploded. Prior to 2010, only one agent – docetaxel – had been shown to extend survival for mCRPC patients. Now, a decade later, we have many such agents beyond docetaxel, including abiraterone, enzalutamide, sipuleucel-T, radium-223, and cabazitaxel. In addition, two other agents have shown significant benefits in other disease settings prior to mCRPC – apalutamide and darolutamide. While all extend survival, in the mCRPC setting the added months of life, on average, range from ~2 to 5. Thus, if all the new agents are added together, it is well over a year of added life. However, can the survival months merely be added together? Alternatively, do you get the biggest bang with the first agents and subsequent agents add little? This is an important unanswered question.
The Use of mpMRI for Preoperative Planning in High-Risk Prostate Cancer and the Impact on Surgical Planning, Cancer Control, and Quality of Life - Commentary
Multiparametric magnetic resonance imaging (mpMRI) is a robust staging modality for high-risk prostate cancer. Less clear is whether pre-operative mpMRI may potentially improve radical prostatectomy outcomes by providing actionable information for planning neurovascular bundle excision, bladder neck sparing, and extent of staging lymph node dissection.
To address this question, these investigators performed a novel, single-center survey study of six urologic oncologists. Study participants were given two surveys incorporating 41 case studies of patients with clinically localized prostate cancer who underwent pre-operative mpMRI prostate followed by robot-assisted laparoscopic prostatectomy and extended pelvic lymph node dissection.
The Association Between Androgen Deprivation Therapy and Autoimmune Diseases in Men with Prostate Cancer - Commentary
The Association of Urinary PCA3 and TMPRSS2:ERG with Biopsy-based Reclassification
The dilemma that resulted from the widespread use of serum prostate-specific androgen (PSA) testing was the identification of a significant number of men with indolent pure red cell aplasia (PrCa). After a significant period of overtreatment, the implementation of active surveillance (AS) has partly solved that issue. However, 25-50 % of AS patients will undergo an intervention. The follow up is rather invasive including serum PSA and repeat biopsies.
Models based on clinical parameters can be used to predict repeat biopsy outcome, yet improved methods to asses the risk to predict adverse pathology are needed. Candidate tools are improved imaging and biomarkers. In the past decade, molecular urine biomarkers were introduced in clinical practice (i.e.Prostate Cancer Gene 3 (PCA3) and TMPRSS2 erg).
Determining Patterns of Disease for Biochemically Recurrent Prostate Cancer by Using 68Ga-PET/CT PSMA - Editorial
This study evaluated 276 men who had undergone a Ga68 PSMA PET/CT for which the majority had PSA biochemical failure (mean PSA 3.60 ng/mL, range 0.01–83 ng/mL). Overall, 86% (239/276) men had positive scans with morethan half having evidence of local disease recurrence. Clearly, there are some limitations given that in the relatively small number of 33 men who underwent a prostate biopsy, only 28 men (85%) were confirmed to histological recurrence. Lymph node metastases were identified in 122 men (44%) of which 49 men had positive lymph nodes that were located outside the template for an extended pelvic lymph node dissection. Bone metastases were documented in 50 men.
Low-carbohydrate Diet Plus Walking to Reduce ADT-induced Metabolic Disturbances Among Prostate Cancer Patients - Commentary
These changes are coupled with a ~40% increased relative risk of diabetes. While exercise can help preserve muscle mass, to date, no treatment has been shown to prevent this metabolic sequela. Given one of the fundamental problems from ADT is problems with controlling sugar, what if people simply didn’t eat sugar?
There is tremendous growth in interest in the ketogenic diet, an extreme form on a low carbohydrate (i.e. sugar) diet. Proponents often tout it as the cure-all for diabetes, obesity, and possibly even cancer. Opponents argue that it is not sustainable, is bad for the environment, and it simply can’t be healthy to eat all that fat. Where
The Efficacy and Morbidity of a Salvage Prostatectomy Series in the Management of Recurrent Prostate Cancer After Radiotherapy - Commentary
In patients with biochemical recurrence after radiation, biopsy-proven localized disease, and no evidence of metastases, salvage prostatectomy may potentially improve survival and delay initiation of androgen deprivation therapy. This National Cancer Institute-sponsored multi-institutional study, CALGB 9687 (Alliance), prospectively evaluated the efficacy and morbidity of salvage prostatectomy in 41 men between 1997 and 2006 (Prostate Cancer Prostatic Dis. 2019 May; 22(2):309-316). At a median follow-up 91 months, these investigators observed robust 2-, 5- and 10-year progression-free survival rates of 51%, 39%, and 33% respectively; and 2-, 5- and 10-year overall survival rates of 100%, 89%, and 52%, respectively.
Understanding Competing Risks for Mortality Among Men with Nonmetastatic Castration-Resistant Prostate Cancer
Recent phase 3 trials suggest that both apalutamide, enzalutamide, and darolutamide can delay metastasis-free survival (MFS) significantly in such men with M0 CRPC who have rapid PSA doubling times (<10 mo) and an elevated PSA of 2.0 or higher. These men may have disease in their prostates or regional nodal
The Association of Gleason Score and Tumor Stage in the Prevalence of DNA Repair Gene Mutations in Localized Prostate Cancer
A straight forward hypothesis is that these mutations have prognostic significance, i.e. mutations in pivotal cancer pathways are associated with clinical-, pathological stage, and grade, which in turn are a good proxy/surrogate for the outcome of the disease. Marshall and colleagues1 focussed on DNA repair gene mutations and ‘mined’ existing DNA sequencing information (TCGA, NatureGenetics via cBioportal) to test this hypothesis. There appeared to be a clear correlation between pathological stage (pT3/4 versus pT2) and Gleason Grade groups (GG ≥ 3 versus GG 1-2). In the cT≥3 ánd GG ≥3 tumors in >20% DNA repair gene mutations were identified. Interestingly there appeared
Endoscopic Enucleation of the Prostate
There have been systematic reviews and meta-analyses evaluating individual energy sources to perform EEP versus transurethral resection of the prostate (TURP). The study by Zhang and colleagues is novel in that for the first time, we have an analysis that takes the stance that all of the EEP techniques are essentially equivalent, and therefore creating a very powerful comparison with TURP.
Statins in Prostate Cancer and the Relationship in Men Undergoing Active Surveillance
Given the presumed importance of cholesterol in cancer pathways (it is the precursor for androgens as well as important in cell signaling pathways), there are multiple reasons to believe statins have anti-prostate cancer properties. While multiple studies have examined the role of statins in prostate cancer, often with mixed results, no prior study has examined this relationship in men undergoing active surveillance.
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