Prostate Cancer and Prostatic Diseases

Can We Better Define the Patients that Benefit from Sipuleucel-T Treatment? - Editorial

It is now a decade ago that Provenge (sipuleucel-T), an autologous active cellular immunotherapy, was approved by the FDA. Many unanswered questions, still needed to be resolved. When to give this to which patient, i.e. timing and predictive patient characteristics are issues that need to be resolved.

Survival of African-American and Caucasian Men after Sipuleucel-T Immunotherapy: Outcomes from the PROCEED Registry

Purpose - African Americans experience greater prostate cancer risk and mortality than do Caucasians. An analysis of pooled phase III data suggested differences in overall survival (OS) between African American and Caucasian men receiving sipuleucel-T. We explored this in PROCEED (NCT01306890), an FDA-requested registry in over 1900 patients with metastatic castration-resistant prostate cancer (mCRPC) treated with sipuleucel-T.

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.

Feasibility of Freehand MRI/US Cognitive Fusion Transperineal Biopsy of the Prostate in Local Anaesthesia as In-Office Procedure— Experience with 400 Patients - Full-Text Article

Background - Transrectal (TR) ultrasound-guided prostate biopsy is one of the most commonly performed urologic procedures worldwide. The major drawback of this approach is the associated risk for infectious complications. Sepsis rates are increasing due to rising antibiotic resistance, representing a global issue. The transperineal (TP) approach for prostate biopsy has recently been adopted at many centres as an alternative to the TR biopsy, and it was shown to be associated with a lower risk for sepsis. The aim of this study was to assess safety and tolerability of TP prostate biopsy performed in local anaesthesia.

Impact of New Systemic Therapies on Overall Survival of Patients with Metastatic Castration-Resistant Prostate Cancer in a Hospital-Based Registry - Full Text Article

Background - In 2004, docetaxel was shown to prolong the overall survival (OS) of patients with metastatic castration resistance prostate cancer (mCRPC). Since 2010, five new systemic therapies have been shown to prolong OS in men with mCRPC. We sought to evaluate the aggregate impact of these newer therapies on the OS of patients with mCRPC.

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.

Impact of Preoperative Prostate Magnetic Resonance Imaging on the Surgical Management of High-Risk Prostate Cancer - Full Text Article

Objective - To evaluate the effect of adding multiparametric magnetic resonance imaging (mpMRI) to pre-surgical planning on surgical decision making for the management of high-risk prostate cancer (HRPC).

Patients and methods - A survey was designed to query multiple centers on surgical decisions of 41 consecutive HRPC cases seen from 2012 to 2015. HRPC was defined by the National Comprehensive Cancer Center Network guidelines. Six fellowship-trained urologic oncologists were asked for their surgical plan in regards to the degree of planned nerve-sparing and lymph node dissection.

The Association Between Androgen Deprivation Therapy and Autoimmune Diseases in Men with Prostate Cancer - Commentary

Many adverse events have been described in men receiving androgen deprivation therapy (ADT), ranging from loss of bone density, hot flushes, cardiovascular risk, metabolic syndrome, cognitive dysfunction, and even less common risks such as deep vein thrombosis and colorectal cancer development. In the January 2019 edition of PCAN, Liu and colleagues describe a novel potential decreased risk of autoimmune diseases with ADT. This is intriguing for several reasons:

Androgen Deprivation Therapy for Prostate Cancer and the Risk of Autoimmune Diseases - Full Text Article

Background - Androgen deprivation therapy (ADT) has been a mainstay of treatment for advanced prostate cancer (PCa), but limited studies have been performed to investigate the association between ADT and autoimmune diseases.

Performance of PCA3 and TMPRSS2: ERG Urinary Biomarkers in Prediction of Biopsy Outcome in the Canary Prostate Active Surveillance Study (PASS)

Background - For men on active surveillance for prostate cancer, biomarkers may improve the prediction of reclassification to a higher grade or volume cancer. This study examined the association of urinary Prostate Cancer Gene 3 (PCA3) and TMPRSS2:ERG (T2:ERG) with biopsy-based reclassification.

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).

The Use of 68Ga-PET/CT PSMA to Determine Patterns of Disease for Biochemically Recurrent Prostate Cancer Following Primary Radiotherapy

Background - 68Ga-PET/CT PSMA scan is being increasingly used for the staging of biochemically recurrent disease. Early identification of recurrent disease after radiotherapy is important in considering suitability for early salvage therapy to improve prognosis. The aim is to identify patterns of suspected prostate cancer recurrence in relation to post-radiotherapy PSA levels, especially below the accepted Phoenix definition of PSA failure (PSA nadir + 2).

Determining Patterns of Disease for Biochemically Recurrent Prostate Cancer by Using 68Ga-PET/CT PSMA - Editorial

This Australian study is the largest published experience of the use of Ga68 PSMA PET/CT imaging in the context of previous primary radiotherapy for prostate cancer. 

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.

A Lifestyle Intervention of Weight Loss via a Low-Carbohydrate Diet Plus Walking to Reduce Metabolic Disturbances Caused by Androgen Deprivation Therapy Among Prostate Cancer Patients: Carbohydrate and Prostate Study 1 (CAPS1) Randomized Controlled Trial

Purpose - The objective of this study was to test a low-carbohydrate diet (LCD) plus walking to reduce androgen deprivation therapy (ADT)-induced metabolic disturbances.

Materials and methods - This randomized multi-center trial of prostate cancer (PCa) patients initiating ADT was designed to compare an LCD (≤20g

Low-carbohydrate Diet Plus Walking to Reduce ADT-induced Metabolic Disturbances Among Prostate Cancer Patients - Commentary

Androgen deprivation therapy (ADT) is standard treatment for advanced and metastatic prostate cancer. While it is very effective for cancer control, it has many side effects. Commonly known side effects include loss of libido, fatigue, osteoporosis, and hot flashes. Additionally, ADT has metabolic side effects. Imagine a young athlete using steroids to have a competitive advantage. They gain muscle mass and lose fat. Now imagine the same man 50 years later undergoing ADT for his prostate cancer – it will have the exact opposite effects – gain of fat mass and loss of muscle mass.

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 - Editorial

Radiotherapy is a mainstay of treatment for localized prostate cancer. Biochemical recurrence after radiotherapy, defined as a prostate-specific antigen (PSA) rise of ≥ 2 ng/mL above nadir, occurs in up to 40% of intermediate- and high-risk patients within 10 years of treatment (Eur. Urol. 67, 1009–1016 (2015). Patients with biochemical recurrence are at increased risks of metastases and death (J. Clin. Oncol. 23, 6992–6998 (2005)).

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.

Management of Recurrent Prostate Cancer After Radiotherapy: Longterm Results from CALGB 9687 (Alliance), a Prospective Multiinstitutional Salvage Prostatectomy Series - Full Text Article

Background - To evaluate efficacy and morbidity prospectively in a contemporary multi-institutional salvage radical prostatectomy (SRP) series.


Methods - Forty-one men were enrolled between 1997 and 2006, who suffered biopsy-proven recurrent prostate cancer (CaP) after receiving ≥ 60c Gy radiation as primary treatment for cT1–2NXM0 disease. Surgical morbidity, quality of life, biochemical progression-free survival (BPFS) and overall survival (OS) were evaluated.

Impact of Age, Comorbidity, and PSA Doubling Time on Long-Term Competing Risks for Mortality Among Men with Non-Metastatic Castration-Resistant Prostate Cancer - Full Text Article

Background - Understanding competing risks for mortality is critical in determining prognosis among men with nonmetastatic castration-resistant prostate cancer (nmCRPC), a disease state that often affects older men and has substantial heterogeneity in risk of cancer mortality. We sought to determine the impact of age, comorbidity, and PSA doubling time (PSADT) on competing risks for mortality in men with nmCRPC.

Understanding Competing Risks for Mortality Among Men with Nonmetastatic Castration-Resistant Prostate Cancer 

A pressing issue facing men with a rising PSA despite hormone therapy is whether to pursue more potent androgen receptor inhibition. While novel PET imaging such as PSMA scans are reducing the size of this M0 CRPC population, this setting remains fairly common in regions of the world where PSA screening is common and men are treated for initially localized prostate cancer. Relapsed disease is first manifested as a PSA rise, and many urologists and oncologists will utilize androgen deprivation therapy (ADT) prior to the onset of visible metastases on standard CT/MRI or technetium bone scans. We know that most of these men have metastases, but these metastases remain small and below the limit of detection of these scans. We also know that most of these men will likely die of metastatic prostate cancer over the next 4-8 years, and therapies that can delay or prevent prostate cancer-specific mortality are needed.

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