PROSTATE CANCER

• ACRONYMS AND DEFINITIONS

• 5ARI - 5-alpha-reductase inhibitor
• ACS - American Cancer Society
• ADT - Androgen deprivation therapy
• ASAP - Atypical small acinar proliferation
• AUA - American Urological Association
• BPH - Benign prostatic hyperplasia
• DRE - Digital rectal exam
• EAU - European Association of Urology
• Gleason score - Pathological grading system used to classify prostate cancer found in prostate biopsies
• GnRH - Gonadotropin-releasing hormone, also referred to as luteinizing hormone–releasing hormone (LHRH)
• mpMRI - Multiparametric MRI - MRI with special images for evaluating the prostate gland
• NCCN - National Comprehensive Cancer Network
• PSA - Prostate specific antigen - protein secreted by the prostate gland
• RCT - Randomized controlled trial
• TURP - Transurethral resection of the prostate
• USPSTF - United States Preventive Services Task Force
• XRT - External-beam radiation

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• EPIDEMIOLOGY

• Excluding skin cancer, prostate cancer is the most common cancer in men in the United States. Approximately 1 in 7 men will be diagnosed with prostate cancer during their lifetime. The average age of diagnosis is 66 years. The National Cancer Institute has a web application that provides current incidence rates for all types of cancer including prostate cancer. The information can be filtered by sex, age, and race. A link to that application is available here - NCI cancer statistic web application
• Prostate cancer is often a slow-growing cancer, and many men die without ever knowing they have it. Autopsies from men who died from other causes have found prostate cancer in 20% of men aged 50 - 59 years and > 33% of men aged 70 - 79 years.
• Prostate cancer-associated mortality typically affects older men with the median age of death from prostate cancer being 80 years. Prostate cancer is the third leading cause of cancer death in American men behind lung and colon cancer. [1,2,3,5]

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• RISK FACTORS

• References [2,3,5,6]

KNOWN RISK FACTORS FOR PROSTATE CANCER
Risk factor	Comments
Age	Age is the number one risk factor for prostate cancer Prostate cancer is rare in men under age 40 The incidence of prostate cancer rises rapidly after age 50
Race	African-Americans have the highest risk of prostate cancer. They also tend to have more aggressive cancers. White men have a moderate risk for prostate cancer Asian-Americans and Hispanics have the lowest risk of prostate cancer
Family history	Family history of prostate cancer is a risk factor for prostate cancer Since a large number of men develop prostate cancer as they age, the number of affected relatives and the age of onset are important factors in quantifying the risk Men with three or more affected relatives or at least two relatives who were diagnosed before the age of 55 are at greatest risk
BRCA2 mutations	BRCA2 mutations occur in families with a high incidence of breast and ovarian cancer. See BRCA gene testing for more. BRCA2 mutations also confer a higher risk of prostate cancer BRCA1 mutations likely increase the risk, but this is less clear

• References [2,3,5,6]

POSSIBLE RISK FACTORS FOR PROSTATE CANCER
Risk factor	Comments
Environment / Geography	Environmental factors appear to play a role in prostate cancer risk Prostate cancer is more common in certain parts of the world (e.g. North America, northwestern Europe, Australia) and less common in others (e.g. Asia, Africa, Central America, South America). The reason is unclear, but screening frequency and longer life expectancy likely contributes to the measured differences.
Diet	A number of studies have looked at a link between prostate cancer and different dietary components (e.g. dairy, fat, alcohol, red meat, vitamin D, etc.). Results from these studies are often conflicting and no definitive link has been confirmed.
Agent Orange	Agent Orange was a defoliant chemical used in the Vietnam War Some studies have suggested a link between Agent Orange exposure and prostate cancer while others have not

• PSA score
• See PSA score and risk of prostate cancer below

• Risk calculator
• A prostate cancer risk calculator is available online. It was developed using data from the placebo cohort in the PCPT trial.
• The calculator is available at the following link - PCPT prostate cancer risk calculator
• The calculator is only valid for the following patients:
• Age ≥ 55 years
• No previous diagnosis of prostate cancer
• DRE and PSA results less than 1 year old

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• SYMPTOMS

• Overview
• Symptoms of prostate cancer are mostly nonspecific and are seen in other common disorders, particularly benign prostatic hypertrophy (BPH)


• Symptoms of prostate cancer include the following:
• Problems urinating - symptoms include weak stream, urinary frequency, nocturia (frequent urination at night), and sensation of not emptying bladder after urination. These symptoms are also seen in BPH, a much more common condition.
• Blood in urine or semen
• Erectile dysfunction - common condition (seen in up to 40% of men 60 - 69 years old)
• Bone pain - may be presenting symptom in advanced metastatic disease [6]

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• PREVENTION

• Overview
• 5-alpha-reductase (5AR) is an enzyme that converts testosterone to dihydrotestosterone (DHT), the primary androgen that stimulates the prostate. 5AR is divided into two subtypes, Type 1 5AR and Type 2 5AR. Type 2 accounts for 70 - 80% of circulating DHT, and Type 1 accounts for the rest.
• Two drugs that inhibit 5AR are currently available in the U.S., finasteride (Proscar) and dutasteride (Avodart). Dutasteride inhibits both Type 1 and Type 2 5AR, while finasteride is selective for Type 2. 5AR inhibitors reduce circulating DHT, which causes the prostate gland to shrink and improves symptoms of BPH. Given their prostate-suppressive effects, there has been interest in using them to prevent prostate cancer. Two large trials that evaluated each drug in prostate cancer prevention are detailed below.

• Summary
• Both finasteride and dutasteride decreased the overall risk of prostate cancer in the two large studies above. Lower urinary tract obstructive symptoms and complications were also lower in 5ARI-treated patients. Paradoxically, the risk of high-grade prostate cancer was greater in 5ARI-treated patients. In the PCPT trial, Gleason 7 - 10 cancers were more common in finasteride-treated patients (6.4% vs 5.1%). In the REDUCE study, the overall incidence of Gleason 7 - 10 cancers was similar between dutasteride-treated patients and placebo, but during years 3 and 4, Gleason 8 - 10 cancers were slightly higher in the dutasteride group (12 vs 1). The reason for these effects is not completely understood. Proposed mechanisms include the following: (1) sampling bias secondary to reduced prostate size in the 5ARI groups, (2) improved sensitivity of PSA testing in patients receiving 5ARIs, (3) 5ARIs selecting for high-grade tumors by inhibiting low-grade tumors, (4) 5ARI-induced histological changes that mimic those of high-grade disease.

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• SCREENING

• Overview
• Screening for prostate cancer has become one of the most controversial topics in healthcare
• Two large studies have shown that prostate cancer screening with the PSA blood test has a minimal effect on prostate cancer mortality. Both studies were somewhat flawed in that there was a significant amount of screening in the control group (crossovers). PSA screening did not affect overall mortality in either study.
• PSA screening is not harmless because it can often lead to procedures and treatments of uncertain value that have a negative effect on quality of life
• Recommendations from professional societies have shifted back and forth over the years as new trial results have been published. Recommendations from the USPSTF, AUA, and EAU are presented below.

• Benefits of screening
• Two large studies have evaluated the risks and benefits of prostate cancer screening. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial took place in the U.S., and The European Randomised Study of Screening for Prostate Cancer (ERSPC) took place in Europe.
• Men in the PLCO study were screened with annual PSA for 6 years and digital rectal exam for 4 years. Screening in the ERSPC trial varied by region with an average PSA screening interval of every 4 years.
• The PLCO trial had a large percentage of crossovers (screening in the control group) with 52% of men in the control group receiving at least one PSA screening. Crossovers in the ERSCP trial were lower (23 - 40%) but not completely known because some centers did not report them. A high number of crossovers can bias a study towards the null, or "no effect."
• Findings for screening from the PLCO, ERSPC, and other trials are detailed below. Like other large-scale screening programs (e.g. colon, breast), prostate cancer screening has never been shown to have an effect on overall mortality.

• Harms of screening
• Harms of prostate cancer screening occur in two ways:
• Adverse events from diagnostic procedures
• Adverse effects of treatment in men who are overdiagnosed
• Adverse events from diagnostic procedures are generally mild. In the ERCP trial where men were screened an average of every four years and most centers used a PSA ≥ 3.0 ng/ml as an indication for biopsy, 15% of men had at least one false-positive test result. Adverse events from prostate biopsy include pain, blood in urine (up to 50%), blood in semen (up to 70%), infection, and rectal bleeding (2%).
• Adverse events from overdiagnosis of prostate cancer are much more substantial. Overdiagnosis occurs when a condition is diagnosed that would otherwise not go on to cause symptoms or death. It's estimated that 20 - 50% of men diagnosed with prostate cancer through screening are overdiagnosed. If these men are treated, they are exposed to unnecessary treatment risks. See prostate cancer treatment side effects below for a review of adverse treatment effects.

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• PSA TEST

• Overview
• Prostate specific antigen (PSA) is a glycoprotein produced by the epithelial cells of the prostatic ducts and acini. PSA is normally present in prostate tissue, prostate fluid, and semen.
• PSA levels in the blood are typically low but can be elevated under certain conditions including the presence of prostate cancer. Benign conditions that may raise blood levels of PSA include prostatitis, benign prostatic hyperplasia (BPH), prostatic trauma (e.g. prostate biopsy, cystoscopy), ejaculation, and digital rectal exams. [12]

• PSA value and risk of prostate cancer
• The PSA blood level has a direct relationship with prostate cancer risk with higher levels indicating greater risk. A PSA value of less than 4 ng/ml is typically used to define a normal range, although lower cutoffs are sometimes seen.
• Even though PSA levels < 4 ng/ml are considered normal, a significant number of men will still have prostate cancer on biopsy at these levels, particularly as they age. The first table below shows the prevalence of prostate cancer at different PSA values among men primarily in their sixties. The second table gives the incidence of prostate cancer over 13 years based on PSA levels drawn at age 55 - 60 years.

• For values ≤ 4 ng/ml, the median age of the cohort was 69 years. Data is from the placebo arm of the PCPT trial.
• For values > 4 ng/ml, the average age of the cohort was 63 years
• Rereneces [10,11]

Prevalence of Prostate Cancer by PSA Value
PSA value	Prostate cancer on biopsy	High-grade prostate cancer (Gleason ≥ 7) on biopsy
≤ 0.5 ng/ml	6.6%	0.82%
0.6 - 1 ng/ml	10%	1.0%
1.1 - 2.0 ng/ml	17%	2.0%
2.1 - 3.0 ng/ml	24%	4.6%
3.1 - 4.0 ng/ml	27%	6.7%
4.0 - 10 ng/ml	26%	-
> 10 ng/ml	53%	-

• ^✝Clinically significant cancer defined as clinical stage ≥ cT2b, Gleason ≥ 7, or prostate-specific mortality
• Data from screening arm of PLCO trial. Cohort size was 10,968 men. In the trial, men were offered annual PSA screening for 6 years.
• References [23]

Incidence of Prostate Cancer Over 13 Years Based on PSA Drawn at Age 55 - 60 Years
PSA (ng/ml)	Prostate cancer	Clinically significant prostate cancer✝
≤ 0.49	0.7%	0.3%
0.5 - 0.99	2.2%	1.1%
1 - 1.99	8.6%	4%
2 - 2.99	21.1%	8.5%
3 - 3.99	33.5%	12.4%
≥ 4	49.9%	23.1%

• Free/Total PSA ratio
• In serum, PSA is found in two forms - free (unbound to proteins) and bound (bound to proteins, mostly protease inhibitors)
• When a PSA is drawn for screening, the total PSA (free + bound) is typically ordered. The free PSA can also be measured, and it is expressed as a percentage of the total PSA.
• For unclear reasons, the percentage of free PSA is typically lower in men with prostate cancer when compared to men without cancer. Because of this association, studies have looked at using the free/total PSA ratio as a predictor of prostate cancer in men with PSA values in the intermediate range (4 - 10 ng/ml). The table below illustrates the results of a study that measured the probability of prostate cancer based on the free/total PSA ratio.
• Currently, no major professional society recommends using the free/total PSA ratio as a predictor for prostate cancer

• Data drawn from a sample of 773 men with normal digital rectal exams and a total PSA between 4 - 10 ng/ml
• Rereneces [13]

% free PSA	Probability of cancer (50 - 64 years old)	Probability of cancer (65 - 75 years old)
0 - 10	56%	55%
10 - 15	24%	35%
15 - 20	17%	23%
20 - 25	10%	20%
> 25%	5%	9%

• PSA velocity
• The rate at which the PSA value increases over time is called the PSA velocity. The "PSA doubling time" is another measure used to quantify changes in PSA values.
• Some studies have found an association between the rate of change in PSA values < 4 ng/ml and prostate cancer. Other studies have not found the measure to be useful.
• In one study that followed 980 men, a PSA velocity of > 0.35 ng/ml per year for values < 4 ng/ml was associated with an increased risk of prostate-cancer death when compared to velocities of ≤ 0.35 ng/ml. [15]
• Current professional guidelines do not recommend using the PSA velocity as a screening tool

• PSA and 5-alpha-reductase inhibitors (5ARIs)
• 5-alpha-reductase inhibitors (finasteride and dutasteride) inhibit the conversion of testosterone to dihydrotestosterone, the primary androgen in the prostate. Finasteride 1 mg (Propecia®) is FDA-approved to treat male pattern baldness, and finasteride 5 mg (Proscar®) is approved for BPH. Dutasteride (Avodart®) is only approved for BPH in the U.S. but is also used off-label for hair loss (see hair loss treatments for more).
• In studies, finasteride (1 mg and 5 mg dose) and dutasteride have been shown to reduce PSA levels by about 50%. To account for this, it is recommended that the measured PSA level be doubled in men taking 5ARIs. The effect of 5ARIs on PSA levels also appears to be time-dependent. In the PCPT trial, PSA levels were doubled during the first 3 years and then multiplied by a factor of 2.3 from year 4 and on. The Free/total PSA ratio, which is also used to detect prostate cancer, is not affected by 5ARIs. [16]

• PSA and post-treatment surveillance
• After prostate cancer diagnosis and treatment, the PSA value is used to monitor for recurrence
• Prostate cancer remission after prostatectomy is defined as a nadir PSA value of ≤ 0.2 ng/ml. After radiation +/- androgen deprivation therapy, remission is defined as a PSA value < 2.0 ng/ml.
• The AUA recommends PSA surveillance for at least 10 years after localized prostate cancer treatment. The frequency of surveillance should be determined by risk of relapse and patient preference. [14]
• The NCCN recommends PSA surveillance every 6 - 12 months for 5 years, then every year. In high-risk men, PSA surveillance as frequently as every 3 months may be necessary to clarify disease status.
• See treatment surveillance below for full recommendations on post-treatment surveillance

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• STAGING

• Overview
• Once a diagnosis of prostate cancer is established, the cancer is then staged in order to help make treatment decisions and determine risk
• Three different clinical values are used to stage prostate cancer:
• The American Joint Committee on Cancer (AJCC) TNM system
• The Gleason score
• The PSA value (see PSA test above)
• The TNM system and Gleason score are reviewed below along with final staging

• TNM categories
• TNM (Tumor, Nodes, Metastasis) categories are based on clinical information gathered from prostate biopsies/removal and radiological studies
• The table below outlines the different categories

• Gleason score
• The Gleason score is a system used to qualify the degree of cancer-like abnormalities seen in a prostate biopsy. Tissue from prostate biopsies is placed on a slide and viewed under a microscope by a pathologist. The pathologist then assigns a Gleason score based on the characteristics of the cells.
• The Gleason grade is the rating a pathologist applies to one sample. It can range from 1 - 5 with 1 meaning the tissue almost appears normal and 5 meaning the tissue is very abnormal. Grades 2 - 4 have features in between these two extremes. Individual prostate cancers are often made up of tissue that has several different grades. Because of this, a Gleason grade is assigned to the two areas of the prostate biopsy that have the most cancer.
• The Gleason score is the sum of the two Gleason grades (e.g. 3+3=6, 4+5=9). Grades 1 and 2 are not generally used in prostate biopsies, so the Gleason score typically has a range from 6 - 10. The first number in the Gleason score is generally the grade that is most predominant in the tumor. For example, a biopsy with a Gleason score of 3+4 would mostly contain Grade 3 tissue with some Grade 4 tissue. If three or more grades are present in a biopsy, the first number is the most predominant grade, and the second number is the highest grade tissue that is observed. For example, if a biopsy contained mostly Grade 3, followed by Grade 4, and even less Grade 5, then the Gleason score would be 3+5.

• Other pathological findings on prostate biopsies
• Atypical Small Acinar Proliferation (ASAP) / Glandular Atypia / Atypical Glandular Proliferation - these terms mean findings are suspicious for cancer, but a definitive cancer diagnosis cannot be made. For men with these findings, the risk of cancer on a second biopsy performed within 6 months is 40%.
• High-grade Prostatic Intraepithelial Neoplasia (PIN) - high-grade PIN is considered pre-cancer, but the risk of prostate cancer is lower than that seen with glandular atypia
• Atypical adenomatous hyperplasia (adenosis) - benign condition not related to prostate cancer [6]

• Cancer stages
• The National Comprehensive Cancer Network (NCCN) Risk Stratification system is primarily used to stage prostate cancer and to determine treatment
• The system combines the TNM category, Gleason score, and PSA value to stratify cancers by risk
• The table below details the system

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• SURVIVAL RATES

• Overview
• Since prostate cancer is typically a slow-growing cancer, survival rates tend to be favorable
• Most men are diagnosed with localized disease (79%), and their risk of death from prostate cancer is lower than their risk of death from other medical conditions
• The table below shows mortality rates based on risk group. It's important to note that survival rates are affected by patient-specific comorbidities, treatment decisions, and evolving treatment options. The survival rates presented below are general values that may vary greatly by individual.

• ¹Data derived from cohort of 3183 U.S. men who were initially diagnosed in 1994-1995. 74% of subjects received either prostatectomy or radiation treatment.
• ²Data from the National Cancer Institue SEER data
• Reference [18,19]

Prostate cancer survival rates based on initial risk group
Risk group	Mortality
Low risk1	3% (14-year prostate cancer-specific mortality)
Intermediate risk1	7% (14-year prostate cancer-specific mortality)
High risk1	18% (14-year prostate cancer-specific mortality)
Metastatic2	70% (5-year overall mortality)

• Survival prediction tools
• The National Cancer Institute has a web application that provides current survival rates for all types of cancer including prostate cancer. The information can be filtered by sex, age, and race. A link to that application is available here - NCI cancer statistic web application
• The online tool listed below estimates survival rates and risk of recurrence based on a handful of variables (e.g. age, PSA, Gleason score, TNM stage, etc.). The tool assumes treatment with radical prostatectomy.
• Memorial Sloan Kettering risk assessment tool

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• TREATMENT

• Overview
• Prostate cancer treatment decisions depend on the stage of disease, patient life expectancy, and considerations of treatment-associated adverse effects
• Treatment options for prostate cancer can be broken down into five categories:
• Surgery (radical prostatectomy)
• Radiotherapy - external beam radiation and brachytherapy (radioactive seeds placed in or near the tumor)
• Active surveillance - monitor disease with curative action if cancer progresses
• Observation - monitor disease with palliative action for symptoms
• Androgen deprivation therapy (ADT)
• Other treatments that are sometimes used, but are less validated in clinical trials and not considered standard of care include:
• Cryotherapy
• High-intensity focused ultrasound (HIFU)

• Professional recommendations
• The table below summarizes treatment recommendations from the National Comprehensive Cancer Network (NCCN) 2017 guidelines. Their most recent and updated guidelines are available on their website - NCCN guidelines.
• In some cases, the guidelines use life expectancy to stratify treatment recommendations. Life expectancy can often be difficult to quantify (see life expectancy for more)

• NCCN active surveillance recommendations
• PSA no more than every 6 months unless clinically indicated
• DRE no more than every 12 months unless clinically indicated
• Repeat prostate biopsy no more than every 12 months unless clinically indicated
• Consider mpMRI if anterior and/or aggressive cancer is suspected when PSA increases and systemic prostate biopsies are negative [17]

• Life expectancy estimation
• Predicting life expectancy is a very inexact science. Patient factors (e.g. comorbid conditions, compliance) and environmental factors (e.g. access to healthcare, support systems, medical advances) all play a role in survival, and their effects can be difficult to quantify.
• The NCCN gives the following recommendations when trying to estimate someone's life expectancy. The recommendations call for using the "clinician's assessment of overall health" which is a highly subjective measure.
• NCCN life expectancy estimation recommendations
• Estimate life expectancy using the Social Security Administration tables - SSA life expectancy tables
• Adjust the estimate using the clinician's assessment of overall health as follows:
• Best quartile of health - add 50%
• Worst quartile of health - subtract 50%
• Middle two quartiles of health - no adjustment [17]

• Robotic vs open prostatectomy
• Prostatectomy can be performed through open surgery where a large incision is made, or it can be performed with a robotic machine controlled by a surgeon that only requires small incisions. The da Vinci Surgical System is a popular machine used to perform robot-assisted prostatectomy.
• In general, studies that have compared robotic to open prostatectomy have found that the two procedures have similar rates of cancer cure, incontinence, and erectile dysfunction
• One advantage of robotic surgeries is that they typically have less blood loss during surgery [14, 17]

• Treatment side effects
• Because of its location around the male urethra and proximity to other important organs and nerves, prostate cancer treatment can have significant side effects
• Since prostate cancer is predominantly a slow-growing cancer, it's important to weigh the potential benefits and risks of treatment when considering active treatment and screening
• Treatment side effects of prostatectomy are primarily erectile dysfunction and urinary incontinence. Treatment side effects of external beam radiation and brachytherapy include erectile dysfunction, urinary symptoms, and bowel symptoms.
• The tables below detail treatment side effects for prostatectomy, external beam radiation, and brachytherapy from the ProtecT study and a prospective cohort study

• Androgen deprivation therapy (ADT)
• Prostate cancer growth is stimulated by testosterone; therefore, lowering testosterone levels in patients with prostate cancer improves survival
• Testosterone deprivation, or ADT, can be achieved through surgery (bilateral orchiectomy) or medications (gonadotropin-releasing hormone (GnRH) agonists and antagonists)
• ADT is recommended in metastatic disease and is sometimes used in combination with radiation therapy for localized disease
• The table below lists some of the common side effects of ADT therapy
• The target testosterone level with ADT is < 50 ng/dL

• Other treatments

• Abiraterone (Zytiga®) - abiraterone is a CYP17 inhibitor. CYP17 is an enzyme required for the synthesis of androgens. Inhibition of CYP17 can also lead to an increase in mineralocorticoid production. Prednisone is given with abiraterone to suppress this effect.
• Abiraterone + Prednisone for Prostate Cancer Not Previously Treated with Hormone Therapy, NEJM (2017)
• Abiraterone + Prednisone in Metastatic, Castration-Sensitive Prostate Cancer, NEJM (2017)
• Abiraterone + Prednisone in Metastatic Prostate Cancer Without Previous Chemo, NEJM (2013)
• Abiraterone + Prednisone in Metastatic Prostate Cancer Previously Treated with Docetaxel, NEJM (2011)

• Adjuvant XRT - adjuvant XRT is radiation therapy that is given soon after prostatectomy to kill any undetected residual disease
  • Adjuvant Radiotherapy vs Observation after Radical Prostatectomy in Patients at Risk for Progression, Lancet (2020)

• Apalutamide (Erleada™) - apalutamide is an androgen receptor antagonist
• Apalutamide vs Placebo for Metastatic, Castration-Sensitive Prostate Cancer, NEJM (2019)
• Apalutamide vs Placebo for Nonmetastatic Castration-resistant Prostate Cancer, NEJM (2018)

• Cabazitaxel (Jevtana®) - cabazitaxel is a chemotherapeutic drug that belongs to the taxane class (e.g. paclitaxel, docetaxel)
• Cabazitaxel vs Abiraterone or Enzalutamide in Metastatic Prostate Cancer, NEJM (2019)

• Darolutamide (Nubeqa™) - darolutamide is an androgen receptor antagonist
• Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer, NEJM (2020)
• Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer, NEJM (2019)

• Enzalutamide (Xtandi®) - enzalutamide is an androgen receptor antagonist
• Enzalutamide vs Placebo in Nonmetastatic, Castration-Resistant Prostate Cancer, NEJM (2020)
• Enzalutamide vs Standard Nonsteroidal Antiandrogen Therapy in Metastatic, Hormone-sensitive Prostate Cancer, NEJM (2019)
• Enzalutamide in Nonmetastatic, Castration-Resistant Prostate Cancer, NEJM (2018)
• Enzalutamide in Metastatic Prostate Cancer before Chemotherapy, NEJM (2014)
• Enzalutamide in Castration-resistant Prostate Cancer after Chemotherapy, NEJM (2012)

• Olaparib (Lynparza®) - olaparib is a PARP inhibitor. PARP is a DNA repair enzyme that certain cancers (e.g. cancers with BRCA mutations) rely on to repair their DNA so they can keep dividing.
• Olaparib vs Enzalutamide or Abiraterone in Metastatic Castration-Resistant Prostate Cancer, NEJM (2020)

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• POST-TREATMENT SURVEILLANCE

• Overview
• After prostate cancer treatment, surveillance for recurrence is recommended
• The table below details the NCCN recommendations for surveillance

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• STUDIES

• STUDY
  MRI-targeted Biopsy vs Standard Biopsy for Prostate Cancer Screening , NEJM (2021) [PubMed abstract]
• Design: Randomized, controlled trial (N=1532) in men aged 50 - 74 years living in Stockholm, Sweden with screening PSA > 3 ng/ml (median PSA 4.26)
• Intervention: MRI-targeted biopsy vs Standard biopsy. Men in the MRI group only underwent biopsy if the MRI results suggested prostate cancer. All men in the standard biopsy group underwent ultrasound-guided biopsy with 10 - 12 cores.
• Primary outcome: Probability of detection of clinically significant prostate cancer, defined as the percentage of participants in each group who received a diagnosis of cancer with a Gleason score of 3+4 or greater (International Society of Urological Pathology grade ≥ 2)
• Results:
• Primary outcome (clinically significant cancer diagnosed): MRI - 21%, Standard - 18% (p<0.001)
• Clinically insignificant cancer diagnosed: MRI - 4%, Standard - 12% (diff -8%, 95%CI[-11 to -5])
• Findings: MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer.

• STUDY
  MRI-targeted Biopsy vs Systematic Biopsy for Prostate Cancer Screening, NEJM (2022) [PubMed abstract]
• Design: Randomized controlled trial (N=17,980) in Swedish men aged 50 - 60 years who agreed to prostate cancer screening with a PSA test
• Intervention: Men with a PSA ≥ 3 ng/ml (N=1201) were randomized to MRI-targeted biopsy (N=796) or MRI-targeted biopsy + systematic biopsy (N=405 | reference group)
• Primary outcome: Clinically insignificant prostate cancer, defined as a Gleason score of 3+3
• Results:
• Primary outcome: MRI-targeted - 0.6%, MRI-targeted + systematic - 1.2% (p<0.001)
• Clinically significant cancer that was detected only by systematic biopsy was diagnosed in 10 participants in the reference group; all cases were of intermediate risk and involved mainly low-volume disease that was managed with active surveillance.
• Findings: The avoidance of systematic biopsy in favor of MRI-directed targeted biopsy for screening and early detection in persons with elevated PSA levels reduced the risk of overdiagnosis by half at the cost of delaying detection of intermediate-risk tumors in a small proportion of patients.

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