Prostate-specific antigen (PSA) test and digital rectal examination (DRE) are 2 screening methods generally used to detect prostate cancer.1 Evidence supports the use of the PSA test as the primary mode of prostate cancer screening.1 DRE may be used as an additional precaution to detect clinically significant cancers that may not be detected by PSA tests alone.1
The emergence of PSA testing as a means for screening for prostate cancer has led to the proliferation of guidance on its appropriate use. The National Comprehensive Cancer Network® (NCCN®), American College of Physicians (ACP), American Cancer Society (ACS), American Urological Association (AUA) and U.S. Preventive Services Task Force (USPSTF) all discuss PSA screening guidance in the context of age, risk factors and individualized patient preferences.1-5
Summary of United States guideline consensus on PSA screening
No guidelines recommend PSA screening in men with life expectancy < 10 years*1-4
No guidelines recommend PSA screening in men < 40 years1-5
All guidelines recommend a shared decision-making approach to PSA screening in eligible men1-5
No guideline consensus exists on screening intervals in appropriate men. Screening intervals range from 1-4 years, depending on PSA level, age and other patient risk factors†1,3,4
PSA cut point
No guideline consensus exists on a universal PSA cut point to trigger biopsy. Cut points range from 4 ng/mL or greater depending on patient risk factors and age‡1,2,4
*Although the USPSTF does not provide direct guidance with regards to PSA screening as it relates to life expectancy, the panel recommends against PSA-based screening for prostate cancer in men 70 years and older.5
†The USPSTF and the ACP do not provide specific guidance on appropriate PSA screening intervals.
‡The USPSTF and the AUA do not provide specific guidance on appropriate PSA cut points.
All screening guidelines recommend a shared decision-making approach to PSA screening.1-5 According to NCCN, this informed decision-making approach is intended to maximize the detection of prostate cancer that requires treatment while minimizing unnecessary procedures and limiting detection of indolent disease.1
2.Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P. Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2013;158(10):761-9.
3.American Urological Association. Early detection of prostate cancer: AUA guideline (2013). https://www.auanet.org/documents/education/clinical-guidance/Prostate-Cancer-Detection.pdf. Accessed 05-07-2018.
4.Wolf AMD, Wender RC, Etzioni RB, et al. American Cancer Society guideline for the early detection of prostate cancer: update 2010. CA Cancer J Clin 2010;60(2):70-98.
5.Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;319(18):1901-13.
Prostate-specific antigen screening debate
The prostate-specific antigen (PSA) screening debate was elevated following a 2012 “D” grade on its use from the U.S. Preventive Services Task Force (USPSTF).1,2 The “D” grade represented a USPSTF recommendation against routine PSA screening in adult men.1 The grade was based on the USPSTF perspective that although there are potential benefits of screening for prostate cancer, these benefits do not outweigh the expected harms.1
Rates of PSA screening declined following the recommendation, and with less screening, incidence rates of early-stage prostate cancer also decreased (Figure).3,4
However, there is evidence to suggest that increases in the detection of high-grade, regionally advanced and metastatic cancers at diagnosis may have coincided with the USPSTF recommendation.5,6 Additionally, higher rates of biochemical recurrence in prostate cancer patients receiving radical prostatectomy have been suggested.6
In 2018, USPSTF changed the grade on PSA screening in healthy men aged 55 through 69 years from “D” to “C” based on an updated review of evidence.1 The revised guidance recommends an informed shared decision-making approach to PSA screening that more closely aligns with other leading guidelines.1,7,8 (See Current screening recommendations.)
1.Grossman DC, Curry SJ, Owens DK, et al. Screening for prostate cancer: US Preventive Services Task Force recommendation statement. JAMA 2018;319(18):1901-13.
2.Prabhu V, Lee T, Loeb S, et al. Twitter response to the United States Preventive Services Task Force recommendations against screening with prostate-specific antigen. BJU Int 2015;116(1):65-71.
3.Jemal A, Fedewa SA, Ma J, et al. Prostate cancer incidence and PSA testing patterns in relation to USPSTF screening recommendations. JAMA 2015;314(19):2054-61.
4.National Cancer Institute. SEER cancer statistics review, 1975-2015 section 23 (04-2018). https://seer.cancer.gov/csr/1975_2015/results_merged/sect_23_prostate.pdf. Accessed 05-30-2018.
5.Weiner AB, Matulewicz RS, Eggener SE, Schaeffer EM. Increasing incidence of metastatic prostate cancer in the United States (2004–2013). Prostate Cancer Prostatic Dis 2016;19(4):395-7.
6.Ahlering T, Huynh LM, Kaler KS, et al. Unintended consequences of decreased PSA-based prostate cancer screening. World J Urol (Epub) 07-12-2018.
For men with newly diagnosed prostate cancer, there are 3 key parameters incorporated into prognostic categories, or risk groups, that help guide therapy.1
The extent that the cancer has spread within the body
TNM staging system
How likely the cancer is to grow and spread quickly
Gleason grade groups
Prostate-specific antigen (PSA)3
A protein that is produced by normal and malignant cells within the prostate gland. PSA is often elevated in the presence of prostate cancer
The most commonly used system for describing the cancer stage is the American Joint Committee on Cancer TNM system.2
Describes the extent of the main (primary) tumor
Describes nearby (regional) lymph nodes that are involved
Describes distant metastasis (the spread of cancer from one part of the body to another)
Numbers or letters after T, N and M provide more details. Higher numbers mean the cancer is more advanced.2
While TNM staging categories articulate the anatomical status of the cancer with a fair amount of specificity, simplified language that broadly describes stages is also used.4
Localized: Cancer is confined to the primary site
Regional: Cancer has spread to regional lymph nodes
Distant: Cancer has metastasized
As the charts show, the vast majority of prostate cancers are localized at diagnosis, and the 5-year survival rate for localized cancer is 100%.4 These statistics lend support to delaying immediate therapeutic intervention in favor of disease monitoring approaches such as active surveillance for men with very low-risk cancer and life expectancy of 20 or fewer years.1
Gleason grade groups
The National Comprehensive Cancer Network® (NCCN®) adopted a new grading system in 2014 that assigns Gleason grade groups from 1 to 5.1 Gleason grade groups are based on a scoring system that describes how likely the cancer is to grow and spread quickly.2 The grade groups are derived from the Gleason scores and correspond to very low, low, intermediate, high and very high risk of disease progression.1 Many thought leaders believe that Gleason grade groups will help patients understand their risk level better and potentially lead to less overtreatment.1
Two studies were conducted to validate the use of the Gleason grading system; one study was in > 26,000 men who had undergone radical prostatectomy or radiation therapy, the other in 5,880 men who had undergone radical prostatectomy or radiation therapy. Both studies concluded that the Gleason grading system provided risk stratification that was as good as or better than the previous Gleason scoring system.5,6
Both the American Society of Clinical Oncology and the American Urological Association have commented on the use of imaging for staging prostate cancer with low risk of metastasis.7 Imaging tests such as computed tomography (CT), positron emission tomography (PET) and bone scans are performed often for staging low-risk cancers, even though there is insufficient clinical evidence supporting improved detection of metastatic disease and survival.7 The progression of prostate cancer to the bone is more common in advanced, aggressive disease; therefore, routine bone scans are unnecessary to perform in low-risk patients.7
To help address this issue, the American College of Radiology published appropriate use criteria that deemed the use of CT and bone scans “generally not recommended” in clinically suspected prostate cancers.8 Further, as part of the American Board of Internal Medicine Foundation’s “Choosing Wisely” campaign, the American Society of Clinical Oncology recommends against using PET, CT and radionuclide bone scans when staging low-risk prostate cancers (stage T1c/T2a, PSA < 10 ng/mL, Gleason score ≤ 6) with low risk of distant metastasis, noting that unnecessary imaging can lead to harm through unnecessary procedures, misdiagnosis and overtreatment.7 Finally, the Centers for Medicare & Medicaid Services has included Avoidance of Overuse of Bone Scans for Staging Low-Risk Prostate Cancer Patients as a validated quality measure in their Physician Quality Reporting System (now the Merit-based Incentive Payment System), a quality reporting program that applies a negative payment adjustment to physicians and practices that do not report data on quality measures satisfactorily.9,10
NCCN prostate cancer staging
NCCN clinical staging is based on the TNM classifications developed by the American Joint Committee on Cancer.1
NCCN risk stratification and staging1
Gleason score ≤ 6/grade group 1 AND
PSA < 10 ng/mL AND
Fewer than 3 prostate biopsy fragments/cores positive, ≤ 50% cancer in each fragment/core** AND
PSA density < 0.15 ng/mL/g
Gleason score ≤ 6/grade group 1 AND
PSA < 10 ng/mL
Gleason score 3 + 4 = 7/grade group 2 OR
PSA 10-20 ng/mL AND
Percentage of positive biopsy cores < 50%
Gleason score 3 + 4 = 7/grade group 2 or Gleason score 4 + 3 = 7/grade group 3 OR
PSA 10-20 ng/mL
Gleason score 8/grade group 4 or Gleason score 4 + 5 = 9/grade group 5 OR
PSA > 20 ng/mL
Primary Gleason pattern 5 OR
More than 4 cores with Gleason score 8-10/grade group 4 or 5
Any T, N1, M0
Any T, any N, M1
#For asymptomatic patients with life expectancy 5 years or less, no further workup or treatment is indicated until the patient becomes symptomatic.1
**Patients with a magnetic resonance imaging lesion that is biopsied and demonstrates grade group 1 cancer (regardless of percentage core involvement or number of cores involved) who otherwise qualify for very low risk should be considered very low risk.1
These risk groups inform treatment strategies and help predict the probability of biochemical recurrence after definitive local therapy.1 In some cases, active treatment may be delayed in favor of active surveillance or observation, depending on risk group, age, health and patient preferences.1
As a complement to risk groups, clinicians may use nomograms to further evaluate risk. Nomograms are algorithms that incorporate relevant prognostic variables to provide additional insight into risk for the individual patient.1 The NCCN has recommended using risk groups as a starting point for exploring treatment options, and then adding nomograms to provide more individualized decision support.1
Shared decision-making is a collaborative process that allows patients and providers to make healthcare decisions together when there is more than one medically reasonable treatment option.1 It takes into account clinical evidence, the relative merits of available treatment options and the patient’s preferences and values. Depending on factors such as age and disease risk, prostate cancer patients may consider forgoing immediate treatment in favor of less invasive approaches, such as observation or active surveillance.2
Some studies have found that shared decision-making may improve patient satisfaction and reduce patients’ selection of elective surgical procedures.3
Support for shared decision-making
The American Urological Association, American College of Physicians and American Cancer Society all recommend shared decision-making approaches for prostate cancer.4-6
Practices that utilize health information technology can support shared decision-making through interactive decision aids, electronic health records, patient portals, personal health records and secure electronic messaging between patients and providers.1 The Agency for Healthcare Research and Quality has developed the SHARE approach as a process that can help healthcare providers and health systems implement shared decision-making.7
Health literacy considerations in shared decision-making
Almost 9 out of 10 American adults may lack proficiency in health literacy. In addition to basic literacy skills, health literacy includes numeracy skills and knowledge of health topics. Health literacy is needed to make informed health decisions based on accessing and understanding health information.8
People with limited health literacy are more likely to report their health status as poor. They have greater healthcare costs due to less frequent use of preventive services, as well as higher hospitalization and emergency department utilization, than people with adequate health literacy skills.8
The U.S. Department of Health and Human Services has recommended a number of strategies providers can use to help improve health decision-making among people with low health literacy skills. They include the use of plain language, limiting the number of messages shared and taking age and social and cultural diversity into account. Ensuring that the health information provided is associated with access to additional services, resources and support is also recommended.8
1.National Learning Consortium. Shared decision making (12-2013). https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf. Accessed 07-20-2018.
3.Stacey D, Légaré F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Data Sys Rev 2017;4:CD001431.
4.Qaseem A, Barry MJ, Denberg TD, Owens DK, Shekelle P. Screening for prostate cancer: a guidance statement from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med 2013;158(10):761-9.
5.American Urological Association. Early detection of prostate cancer: AUA guideline (2013). https://www.auanet.org/documents/education/clinical-guidance/Prostate-Cancer-Detection.pdf. Accessed 05-07-2018.
6.American Cancer Society. American Cancer Society prevention and early detection guidelines. https://www.cancer.org/healthcare-professionals/american-cancer-society-prevention-early-detection-guidelines.html. Accessed 07-20-2018.
7.Agency for Healthcare Research and Quality. The SHARE approach: putting shared decisionmaking into practice: a user’s guide for clinical teams. https://www.ahrq.gov/sites/default/files/wysiwyg/professionals/education/curriculum-tools/shareddecisionmaking/tools/tool-8/share-tool8.pdf. Accessed 01-16-2019.
8.U.S. Department of Health and Human Services. Quick guide to health literacy. https://health.gov/communication/literacy/quickguide/Quickguide.pdf. Accessed 09-04-2018.
Active surveillance is recommended in men with very low-risk prostate cancer and life expectancy up to 20 years.1 It involves ongoing routine monitoring and regular follow-up, including digital rectal examination no more than once a year and prostate-specific antigen testing no more than twice a year.1 It may also include surveillance biopsies of the prostate.1 Active surveillance is undergone with the expectation to transition the patient to curative treatment if the cancer progresses.1
Observation is recommended for patients with low-risk prostate cancer with life expectancy less than 10 years.1 Observation involves monitoring the course of disease for opportunities to provide palliative therapy if symptoms develop or are imminent.1 Active surveillance and observation may help patients avoid the possible side effects of unnecessary definitive treatment as well as the early initiation or continuous use of androgen deprivation therapy (ADT).1
Surgery and radiation are local therapies that target specific areas of the body.2 For men diagnosed with early-stage prostate cancer, these therapies may eliminate the cancer completely.2 At this treatment stage, a radical prostatectomy may be performed, removing the entire prostate and seminal vesicles.2 Local therapies are often the first step in the active treatment of prostate cancer, except in cases where patients present with locally advanced or metastatic disease.1
Androgen deprivation therapy
Androgen hormones such as testosterone drive prostate cancer growth; lowering a patient’s levels of these hormones may slow the growth of the cancer.2 Surgical castration (bilateral orchiectomy) or medical castration (luteinizing hormone-releasing hormone [LHRH] agonist or antagonist), known as ADT, decreases endogenous androgen production in men with locally advanced, recurrent or metastatic disease.2 LHRH agonists/antagonists are versatile therapy options for prostate cancer; depending on clinical inputs, they may be administered continuously or intermittently; as short- or long-term treatments; and as neoadjuvant, concurrent, adjuvant or primary therapies.1,2 ADT adverse effects may include hot flashes, loss of libido, obesity, loss of muscle mass, depression and/or fatigue, osteoporosis and greater incidence of fractures.1 Many of these adverse effects may resolve upon discontinuation of ADT treatment, except in patients who have had an orchiectomy.2 However, for some patients who have received ADT for several years, certain adverse effects may persist after drug discontinuation, such as metabolic syndrome, which may include obesity, diabetes and/or cardiovascular disease.2 Management of adverse effects is important for patients receiving ADT.2
Secondary hormonal therapy
Patients may progress despite ADT as mutations at a cellular level facilitate tumor growth even at low androgen concentrations.3 Disease progression on ADT (LHRH therapy or prior bilateral orchiectomy) is called castration-resistant prostate cancer (CRPC).4 For men with metastatic CRPC, secondary hormonal therapy has been shown to extend overall survival despite progression on ADT; for men with nonmetastatic CRPC, data supports that secondary hormone therapy extends metastasis-free survival.1 This category of treatment is used in combination with traditional ADT (ie, ADT plus antiandrogen) and seeks to further suppress endogenous androgen production.1 Comprehensive evaluation of a patient’s disease state for clinical evidence of nonmetastatic vs metastatic or asymptomatic vs symptomatic disease is a critical factor when selecting a treatment.1
First-line chemotherapy for prostate cancer is given intravenously with steroids.2 This therapeutic combination has been shown to increase the overall survival of patients with metastatic CRPC.1 Chemotherapy is associated with significant adverse events that may necessitate increased palliative care.2 It also requires infusion-related services that may add costs, such as physician and infusion center visits.5 When used in conjunction with or following ADT, primary chemotherapy can effectively reduce recurrence and improve survival in patients.2
Treatment guidelines recommend second-line chemotherapies following progression on first-line chemotherapy only, as they are less effective at improving overall survival than first-line chemotherapies.1 Second-line chemotherapies may be helpful as palliative therapies for controlling pain.1
Immunotherapy treatment amplifies a patient’s natural immune response to target prostate cancer cells.2 This therapy is highly individualized, isolating immune cells that are modified in vitro and then placed back in the patient.2 The effectiveness of immunotherapy can be difficult to measure because there is no effect on prostate-specific antigen levels.2 Results from clinical trials have shown that immunotherapy may increase survival in men with minimally symptomatic or asymptomatic metastatic CRPC.2
After appropriate trials of other therapeutic approaches, subsequent treatments may be pursued.1 Treatments targeting bone metastases can reduce pain and improve survival in patients with CRPC who have symptomatic bone metastases but no known visceral metastatic disease.1,2 Patients whose cancer has progressed following standard therapies may be encouraged to enroll in clinical trials.2 Palliative care is an important consideration in advanced prostate cancer to help minimize patient suffering and is a critical aspect of a patient’s overall treatment plan.2
2.American Society of Clinical Oncology. Prostate cancer: treatment options (03-2018). https://www.cancer.net/cancer-types/prostate-cancer/treatment-options. Accessed 08-21-2018.
3.Visakorpi T, Hyytinen E, Koivisto P, et al. In vivo amplification of the androgen receptor gene and progression of human prostate cancer. Nat Genet 1995;9(4):401-6.
4.Eisenberger MA, Saad F. Introduction – castration resistant prostate cancer: a rapidly expanding clinical state and a model for new therapeutic opportunities. In: Saad F, Eisenberger MA, eds. Management of Castration Resistant Prostate Cancer. 1st ed. New York. NY: Springer, 2014:3-8.
5.Crawford ED, Black L, Eaddy M, Kruep EJ. A retrospective analysis illustrating the substantial clinical and economic burden of prostate cancer. Prostate Cancer Prostatic Dis 2010;13(2):162-7.
Clinical guidelines and recommendations
Appropriate treatment sequencing, screening strategies, imaging criteria and monitoring protocols all play important roles in the effective management of prostate cancer.
Select U.S. clinical guidelines and recommendations related to prostate cancer
AUA/American Society for Radiation Oncology/Society of Urologic Oncology: Clinically Localized Prostate Cancer Guideline1
NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer2
ASCO Clinical Practice Guideline on Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer3
AUA Guideline on CRPC4
ASCO I and Cancer Care Ontario Clinical Practice Guideline on Systemic Therapy in Men With Metastatic CRPC5
ASCO II Provisional Clinical Opinion on Second-line Hormonal Therapy for Men With Chemotherapy-naïve CRPC6
RADAR II: The Role of Therapeutic Layering in Optimizing Treatment for Patients With CRPC7
Monitoring, staging or progression
RADAR I: Challenges and Recommendations for Early Identification of Metastatic Disease in Prostate Cancer8
ACR Appropriateness Criteria Prostate Cancer—Pretreatment Detection, Surveillance and Staging9
ACR, American College of Radiology; ASCO, American Society of Clinical Oncology; AUA, American Urological Association; CRPC, castration-resistant prostate cancer; NCCN, National Comprehensive Cancer Network; PSA, prostate-specific antigen; RADAR, Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence.
There are multiple guidelines on prostate cancer treatment and sequencing.1-7 NCCN, AUA, ASCO and the RADAR Group have all issued recommendations on this subject.1-7 Of these guidelines, the NCCN guidelines provide the most comprehensive overview of the treatment continuum, with other guidelines focusing on early- or late-stage disease.1,2,5 Although guidelines are generally aligned, sequencing recommendations are not always clear, highlighting the importance of evaluating patient-specific factors and access to therapeutic options in this space.2,7
Monitoring, staging or progression
The emergence of PSA screening has led to increased detection rates of prostate cancer at earlier stages.10,11 Additionally, PSA test results supply healthcare providers with valuable information to help determine the stage and extent of disease.12 (See Prostate cancer risk grouping.) As a result, the majority of prostate cancer cases present at the localized phase, diminishing the need for widespread diagnostic imaging.1
To curb the overuse of imaging in low-risk disease, which can lead to unnecessary healthcare utilization and costs, the ACR has released guidance on appropriate use criteria for imaging in prostate cancer.2,9 The guidance has garnered widespread support, even forming the genesis of the Centers for Medicare & Medicaid Services Physician Quality Reporting System quality measures (now administered through the Medicare Access and Children’s Health Insurance Program [CHIP] Reauthorization Act Merit-based Incentive Payment System Quality Payment Program).1,2,13-15
Contrary to early-stage disease, routine imaging can play an important role in monitoring late-stage disease.8 Many governing bodies have previously released guidance on monitoring for metastatic disease, but variability exists between guidelines.8 In 2014, the RADAR Group issued guidance that sought to standardize eligibility criteria, type of imaging modality and frequency of scanning for detecting metastatic disease.8 The recommendations aim to identify metastatic prostate cancer earlier in the disease continuum, which may influence treatment approaches.8
3.Morris MJ, Rumble RB, Basch E, et al. Optimizing anticancer therapy in metastatic non-castrate prostate cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol 2018;36(15):1521-39.
5.Basch E, Loblaw DA, Oliver TK, et al. Systemic therapy in men with metastatic castration resistant prostate cancer: American Society of Clinical Oncology and Cancer Care Ontario clinical practice guideline. J Clin Oncol 2014;32(30):3436-48.
6.Virgo KS, Basch E, Loblaw DA, et al. Second-line hormonal therapy for men with chemotherapy-naïve, castration-resistant prostate cancer: American Society of Clinical Oncology provisional clinical opinion. J Clin Oncol 2017;35(17):1952-64.
7.Crawford, ED, Petrylak DP, Shore N, et al. The role of therapeutic layering in optimizing treatment for patients with castration-resistant prostate cancer (prostate cancer radiographic assessments for detection of advanced recurrence II). Urology 2017;104:150-9.
8.Crawford ED, Stone NN, Yu EY, et al. Challenges and recommendations for early identification of metastatic disease in prostate cancer. Urology 2014;83(3):664-9.
9.Coakley FV, Oto A, Alexander LF, et al. ACR Appropriateness Criteria® prostate cancer—pretreatment detection, surveillance, and staging. J Am Coll Radiol 2017;14(Suppl 5):S245-57.
10.Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR. The changing face of low-risk prostate cancer: trends in clinical presentation and primary management. J Clin Oncol 2004;22(11):2141-9.
11.Surveillance, Epidemiology, and End Results Program. Cancer stat facts: prostate cancer. https://seer.cancer.gov/statfacts/html/prost.html. Accessed 10-19-2018.
12.American Cancer Society. Tests for prostate cancer (05-15-2017). https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/how-diagnosed.html. Accessed 09-10-2018.
13.American Board of Internal Medicine. Choosing wisely. http://www.choosingwisely.org/wp-content/uploads/2015/01/Choosing-Wisely-Recommendations.pdf. Accessed 09-04-2018.
14.Centers for Medicare & Medicaid Services. 2016 radiology preferred specialty measure set (01‐06‐2016). https://www.cms.gov/Medicare/Quality‐Initiatives‐Patient‐Assessment‐Instruments/PQRS/downloads/Radiology_Specialty_Measure_Set.pdf. Accessed 09‐04‐2018.
15.American Society for Radiation Oncology. Quality Payment Program final rule summary. https://www.astro.org/uploadedFiles/_MAIN_SITE/Daily_Practice/Medicare_Payment_Initiatives/MACRA/Content/MACRAFinalRuleSummary.pdf. Accessed 08‐30‐2018.
Identifying and treating recurrence
The methods used to identify prostate cancer recurrence as well as subsequent treatment options are informed by the initial treatment—either radical prostatectomy or local radiation therapy.1
Recurrence after radical prostatectomy
If the patient has had a radical prostatectomy, there are 2 potential
indicators of recurrence2
Prostate-specific antigen (PSA) persistence—PSA has not fallen to an undetectable level after the radical prostatectomy
PSA recurrence—PSA was undetectable after the radical prostatectomy; then there are 2 consecutive subsequent PSA increases
The National Cancer Comprehensive Network® (NCCN®) Guidelines recommends use of PSA doubling time as a test for confirming the extent of the recurrence in this context.1 Simply put, PSA doubling time is the time needed to reach a 2-fold PSA increase.*2 Possible additional tests include chest x-ray, computed tomography or magnetic resonance imaging scan, transrectal ultrasonography, bone scan, positron emission tomography scan and biopsy.1
If testing reveals no distant metastases, the NCCN guideline–recommended therapeutic options are1
External beam radiation therapy with or without androgen deprivation therapy (ADT)
If distant metastases are found, the guidelines recommend either ADT with or without external beam radiation therapy to the distant site or observation.1
Recurrence after local radiation therapy
If the patient has had local radiation therapy as the initial treatment, recurrence can be identified through biochemical failure (PSA levels increasing by a certain amount compared to their lowest level after initial therapy) or a positive digital rectal examination.2 The main NCCN-recommended tests for determining the extent of the recurrence are PSA doubling time, chest x-ray, bone scan and prostate magnetic resonance imaging.1
Therapeutic options will depend on test results and whether the patient is a candidate for local therapy (criteria are low stage, life expectancy of more than 10 years and PSA levels below a certain threshold).1 The following options are recommended if the patient meets the criteria for local therapy2:
Observation, ADT or clinical trials are recommended when no cancer is found in the prostate or other sites
Observation, radical prostatectomy with pelvic lymph node dissection, cryosurgery, high-intensity focused ultrasound or brachytherapy are recommended when cancer is found in the prostate but not in other sites
ADT with standard chemotherapy or with an androgen synthesis inhibitor is recommended if the cancer has metastasized
ADT or observation is also recommended for patients with recurrence who are not candidates for local therapy.2
Progression after therapy for recurrence
Patients who continue to progress may be candidates for orchiectomy (removal of the testicles) or a variety of systemic therapies, including advanced hormonal therapy in combination with ADT or chemotherapy.1 (See Therapeutic continuum.)
Therapy selection is based on the presence and extent of metastasis and whether or not the cancer is castration resistant,1 that is, a cancer that continues to progress despite therapies that lowered testosterone levels.2
*PSA doubling time is calculated using a linear regression model of the normal algorithm of PSA and time, based on a minimum of 3 consecutive PSA values with each value ≥ 20 ng/mL, inclusion of the most recent PSA values during ADT and the interval between the first and last PSA values of ≥ 8 weeks but ≤ 12 months.3
3.Scher HI, Morris MJ, Stadler WM, et al. Trial design and objectives for castration-resistant prostate cancer: updated recommendations from the Prostate Cancer Clinical Trials Working Group 3. J Clin Oncol 2016;34(12):1402-18.
The need for more efficient care coordination has become a top priority for healthcare stakeholders in recent years. To improve health outcomes and achieve cost savings, the U.S. healthcare system has begun moving toward value-based care models.1-4 In particular, payers have begun to shift cost accountability to other stakeholders in an effort to promote better interdisciplinary communication and coordination.4 As reimbursement models evolve to reward quality and cost-effectiveness, the care coordinator’s role is poised to become even more important.4
The Oncology Care Model
The Oncology Care Model (OCM) program, endorsed by the Centers for Medicare & Medicaid Services (CMS), is a value-based care model.4 The median age at prostate cancer diagnosis is about 66 years.5 As this is similar to the age for starting Medicare coverage,6 changes to CMS reimbursement management could affect how care is delivered to many prostate cancer patients. In addition, as the largest payer in the United States, models promoted by CMS can have a major influence over the policies of private sector payers.7
The aim of the OCM is to use appropriately aligned financial incentives to improve care coordination, appropriateness of care and access to care for patients receiving chemotherapy. OCM encourages participating practices to improve care and lower costs through an episode-based payment model that financially incentivizes high-quality, coordinated care.4
The OCM defines the following 5 focus areas or secondary drivers, which include recommended and required activities for achieving the strategy of the primary driver, comprehensive coordinated cancer care8:
While a care coordinator could potentially play a role within any of these focus areas, providing the core functions of patient navigation is a CMS requirement within the care coordination focus area.8
How the OCM defines patient navigation core functions
The core functions of patient navigation are defined in the OCM as8
Coordinating appointments with clinicians inside and outside the practice to ensure timely delivery of diagnostic and treatment services
Maintaining communication with patients and families across the care continuum
Ensuring appropriate medical records are available at scheduled appointments
Arranging language translation or interpretation services
Facilitating connections to follow-up services
Providing access to clinical trials
Building partnerships with local agencies and groups (eg, cancer survivor support groups); maintaining a list of community and social services available to patients
The OCM definition of nurse navigation is based on services included in the National Cancer Institute’s Patient Navigation Research Program, which found that patient navigation8,9
Increased resolution rates for abnormal screening findings
Decreased time between abnormal screening and diagnostic resolution
Increased treatment initiation rates among patients at risk for delaying the start of treatment within 90 days of cancer diagnosis
Improved quality of life and satisfaction with the healthcare system and cancer care, compared with patients who did not receive navigation services
1.The Patient Protection and Affordable Care Act, Public Law 111-148, 111th Congress (03-23-2010). https://www.gpo.gov/fdsys/pkg/PLAW-111publ148/pdf/PLAW-111publ148.pdf. Accessed 08-30-2018.
2.Centers for Medicare & Medicaid Services. Pioneer ACO Model (08-28-2018). https://innovation.cms.gov/initiatives/Pioneer-ACO-Model/. Accessed 09-04-2018.
3.Burwell SM. Setting value-based payment goals — HHS efforts to improve U.S. health care. N Engl J Med 2015;372(10):897-9.
4.Centers for Medicare & Medicaid Services. Oncology Care Model (08-28-2018). https://innovation.cms.gov/initiatives/oncology-care/. Accessed 09-04-2018.
5.Surveillance, Epidemiology, and End Results Program. Cancer stat facts: prostate cancer. https://seer.cancer.gov/statfacts/html/prost.html. Accessed 10-19-2018.
6.Medicare.gov. When will my coverage start? https://www.medicare.gov/sign-up-change-plans/how-do-i-get-parts-a-b/when-will-my-coverage-start. Accessed 09-04-2018.
7.Troy TD. How the government as a payer shapes the health care marketplace (2015). http://www.americanhealthpolicy.org/Content/documents/resources/Government_as_Payer_12012015.pdf. Accessed 08-30-2018.
8.Centers for Medicare & Medicaid Services. Oncology Care Model: key drivers and change package (06-01-2018). https://innovation.cms.gov/Files/x/ocm-keydrivers-changepkg.pdf. Accessed 07-26-2018.
9.National Cancer Institute. Patient navigation research program (PNRP). https://www.cancer.gov/about-nci/organization/crchd/disparities-research/pnrp. Accessed 09-04-2018.
Due to the seriousness of a cancer diagnosis, clinicians may assume that nonadherence to oral oncolytics is not as prevalent as in other disease states.1 However, research shows that adherence to some oral oncology medications can be surprisingly low.2
Nonadherence can be defined as a patient missing doses, taking medication in the wrong quantity or not filling prescriptions.3
Consequences of nonadherence
Nonadherence negatively impacts the success of treatment.2 Poor treatment adherence is associated with increased medical costs, poor clinical outcomes and higher hospitalization rates.1,2 Additionally, nonadherence in the form of prescription abandonment may result in medication waste and decreased cost savings.4
Barriers to adherence
Treatment regimen complexity is a major barrier to adherence.5 Patients who take several medications simultaneously are at an increased risk for oral oncology prescription abandonment.5
Another potential barrier to patient adherence is health literacy.6 More than one-third of American adults may have basic or below-basic health literacy.6 In addition to basic literacy skills, health literacy includes numeracy skills and knowledge of health topics.7
Poor health literacy may affect a patient’s ability to understand and follow instructions on how to take their medication correctly.6 To mitigate this potential barrier, patients may benefit from conversations with their healthcare providers, who can help them understand the treatment’s potential benefits and dose and what to do if adverse events occur.8 In addition, specialty pharmacies can be a resource to help support medication adherence, educating patients on the therapy and how to take the medicine correctly.9
1.Darkow T, Henk HJ, Thomas SK, et al. Treatment interruptions and non-adherence with imatinib and associated healthcare costs: a retrospective analysis among managed care patients with chronic myelogenous leukaemia. Pharmacoeconomics 2007;25(6):481-96.
2.Ganesan P, Sagar TG, Dubashi B, et al. Nonadherence to imatinib adversely affects event free survival in chronic phase chronic myeloid leukemia. Am J Hematol 2011;86(6):471-4.
3.Bestvina CM, Zullig LL, Rushing C, et al. Patient-oncologist cost communication, financial distress, and medication adherence. J Oncol Pract 2014;10(3):162-7.
4.Khandelwal N, Duncan I, Ahmed T, Rubinstein E, Pegus C. Impact of clinical oral chemotherapy program on wastage and hospitalizations. J Oncol Pract 2011;7(3 Suppl):e25s-9s.
5.Streeter SB, Schwartzberg L, Husain N, Johnsrud M. Patient and plan characteristics affecting abandonment of oral oncolytic prescriptions. J Oncol Pract 2011;7(suppl 3):46S-51S.
6.U.S. Department of Health and Human Services. America’s health literacy: why we need accessible health information (2008). https://health.gov/communication/literacy/issuebrief/#conclusion. Accessed 01-28-2019.
7.U.S. Department of Health and Human Services. Quick guide to health literacy. https://health.gov/communication/literacy/quickguide/Quickguide.pdf. Accessed 09-04-2018.
8.Nunes V, Neilson J, O’Flynn N, et al. Interventions to increase shared decision-making about medicines. In: Nunes V, Neilson J, O’Flynn N, et al. Medicines Adherence: involving patients in decisions about prescribed medicines and supporting adherence. London, UK: National Collaborating Centre for Primary Care and Royal College of General Practitioners, 2009:63-154.
9.National Association of Specialty Pharmacy. NASP definitions of specialty pharmacy and specialty medications (02-24-2016). http://naspnet.org/wp-content/uploads/2016/06/633570_864cb572b8b042909a3f207eaf764d7a.pdf. Accessed 09-12-2018.
Patient financial considerations
Patients with cancer are being treated with expensive chemotherapies and biologic drugs more frequently; prices higher than $10,000 per month are not uncommon for such agents.1 As costs have increased, insurers have increasingly shifted them to patients, in the form of higher premiums, deductibles, coinsurance and copayments.1
Cancer survivors have higher out-of-pocket costs than people who have never had cancer, related to the costs of ongoing cancer care and care for late onset or chronic treatment-related impairments.1 Asset depletion and personal debt related to cancer care are not uncommon.1
According to the National Cancer Institute:
Care coordinators such as nurse navigators can help patients address financial and insurance-related barriers to care. They can also help identify and refer patients to local and national resources that can help mitigate their financial burden.2
Medicare Part D Low-Income Subsidy
The Medicare Part D Low-Income Subsidy Program assists qualified low-income seniors or disabled individuals by capping the out-of-pocket costs of both brand and generic prescription drugs.3-5 Low-Income Subsidy Program enrollees constitute approximately 28% of total Medicare Part D 2018 beneficiaries.6
1.National Cancer Institute. Financial toxicity and cancer treatment (PDQ®)–health professional version (01-30-2018). https://www.cancer.gov/about-cancer/managing-care/track-care-costs/financial-toxicity-hp-pdq. Accessed 09-04-2018.
3.American Cancer Society. Programs that help pay for prescription drugs (06-12-2017). https://www.cancer.org/treatment/finding-and-paying-for-treatment/understanding-health-insurance/if-you-have-trouble-paying-a-bill/prescription-drug-assistance-programs/if-you-need-financial-help.html. Accessed 09-04-2018.
4.Social Security Administration. HI 03001.020 Eligibility for extra help (prescription drug low-income subsidy) (02-07-2018). http://policy.ssa.gov/poms.nsf/lnx/0603001020. Accessed 09-04-2018.
5.National Council on Aging. Low-income subsidy (LIS)/extra help (2018) (02-2018). https://www.ncoa.org/wp-content/uploads/part-d-lis-eligibility-and-benefits-chart.pdf. Accessed 09-04-2018.
6.Centers for Medicare & Medicaid Services. 2018 Annual Report of the Boards of Trustees of the Federal Hospital Insurance and Federal Supplementary Medical Insurance Trust Funds (06-05-2018). https://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/ReportsTrustFunds/Downloads/TR2018.pdf. Accessed 09-04-2018.
Prostate cancer patients may experience a variety of psychosocial stressors.1 The emotional toll of living with cancer, the potential for cancer recurrence and the daily management of adverse events and treatment-related physical impairments are associated with new or exacerbated psychological illnesses, such as depression, anxiety or post-traumatic stress disorder.1 Psychological impairments may also create socioeconomic problems, such as the reduced capacity to work or fulfill other common social roles.1
Psychosocial stressors are thought to negatively impact health in several ways.1
Emotional distress and mental illnesses cause suffering, poorer health and poorer functioning1
Psychosocial stressors can limit the patient’s capacity to manage his illness, including accessing healthcare resources, adhering to treatment regimens and monitoring symptoms and adverse events1
The psychosocial issues that arise may depend on the phase of prostate cancer progression; providing effective intervention requires an understanding of how patients are affected at each phase.2
When psychosocial stressors overwhelm the patient’s own psychological resources or those of his informal social network, professional intervention may be needed.1 The effectiveness of therapies for emotional distress or illnesses like depression or anxiety is well documented.1 Socioeconomic support measures, such as assistance with transportation or medication financial assistance programs, are widely acknowledged to be helpful interventions.1 Nurse navigation can be a resource to help identify and refer patients to psychosocial support services available within their health systems and their wider communities.3
1.Adler NE, Page AEK, eds. Cancer care for the whole patient: meeting psychosocial health needs. Washington, DC: National Academies Press, 2008.
2.Northouse LL, Mood DW, Montie JE, et al. Living with prostate cancer: patients’ and spouses’ psychosocial status and quality of life. J Clin Oncol 2007;25(27):4171-7.
3.Centers for Medicare & Medicaid Services. Oncology Care Model: key drivers and change package (06-01-2018). https://innovation.cms.gov/Files/x/ocm-keydrivers-changepkg.pdf. Accessed 07-26-2018.
Informal cancer patient caregiving can come from friends, neighbors or members of the patient’s spiritual community. However, spouses, life partners or adult children are typically the primary caregivers of cancer patients.1
Primary caregivers provide significant amounts of emotional and logistical support to the patient, often at risk to their own health.1 Primary caregivers may experience depression and other adverse health events as well as higher risk of premature death.1 Spouses who are under strain from the support they provide are 63% more likely to die within 4 years than other people their age.1
Furthermore, caregivers’ emotional distress can directly affect that of the patient, which may lead to reciprocity in emotional distress and mental health disorders between the patient and the primary caregiver.1
In one study, researchers assessed the psychosocial status of prostate cancer patients and their spouses during 3 phases of prostate cancer—newly diagnosed, biochemical recurrence and advanced disease.2 Although psychosocial effects were more likely to be linked to the phase of the disease than the person's role as patient or caregiver, the following differences were observed2:
In the biochemical recurrent phase, caregivers reported more uncertainty about the illness than patients2
In the advanced phase, caregivers experienced lower emotional quality of life than patients2
Across all 3 phases, caregivers experienced less self-efficacy (ie, less confidence in managing the effects of prostate cancer) and less social support2
It is important to note that lower levels of self-efficacy in spouses vs patients may be the result of receiving less social support throughout all phases of the illness.2 In addition, the risk for distress among spouses matches that of patients, demonstrating that they are impacted by the effects of the illness.2
These results underscore the need to identify and provide supportive services to distressed primary caregivers, not only for the sake of their own health and quality of life, but also for the well-being of the patient.1,2 The National Academy of Medicine (formerly known as the Institute of Medicine) recommends that patients and their families be provided with information about the cancer, its treatment and their effects on health, as well as information about psychosocial support services available to them.1
1.Adler NE, Page AEK, eds. Cancer care for the whole patient: meeting psychosocial health needs. Washington, DC: National Academies Press, 2008.
2.Northouse LL, Mood DW, Montie JE, et al. Living with prostate cancer: patients’ and spouses’ psychosocial status and quality of life. J Clin Oncol 2007;25(27):4171-7.
According to the current definition, anyone who has been diagnosed with cancer qualifies as a cancer survivor.1 That means that a patient becomes a survivor at the point of diagnosis and remains so for the rest of the patient’s life.1 Identifying, understanding and addressing secondary effects of cancer on the survivor are important for improving quality outcomes within this population.1
Understanding the challenges of prostate cancer survivors
Surgery and radiotherapy are two common treatments for prostate cancer.1 These approaches are associated with risk of substantial physical impairments.1 According to one long-term follow-up study*2
More than 95% of men experience at least some sexual dysfunction
50% of men experience at least some urinary and bowel dysfunction
Androgen deprivation therapy (ADT) is another therapy for prostate cancer, especially in patients with advanced disease.1 Patients receiving ADT may experience short- and long-term consequences to therapy.1
Potential short-term consequences of ADT1
Loss of libido
Gynecomastia (development of male breasts)
Potential long-term consequences of ADT1
Failure to recognize and treat these complications can lead to poorer overall health outcomes.3
A cancer survivor’s quality of life generally improves over time, especially with cessation of treatment.1 However, it is still important to actively monitor survivor well-being.1 Many survivors or their caregivers report1,3,4
Anxiety about cancer recurrence and subsequent primary cancers
Pain that may affect mobility, sleep and work
It is important to consider survivorship care from a long-term and comprehensive vantage point to restore a satisfactory quality of life for those affected.1 (See Psychosocial considerations.)
*Based on an observational analysis that examined 529 prostate cancer survivors and 514 matched controls. Patients completed the Expanded Prostate Cancer Index Composite Short Form, which evaluates health-related quality of life based on urinary, bowel, sexual and hormonal functioning. Patients in the prostate cancer arm had documented prostate cancer diagnosis ≥ 5 to less than 10 years before participating in a health-related quality of life interview and were stratified into 3 groups based on prostate cancer treatment history: 1) surgery only (n = 201), 2) radiation only (n = 110) and 3) combination therapy (n = 207), which included men who had received hormone therapy only as well as any combination of surgery, radiotherapy or hormone therapy.2
1.Miller KD, Siegel RL, Lin CC, et al. Cancer treatment and survivorship statistics, 2016. CA Cancer J Clin 2016;66(4):271-89.
2.Taylor KL, Luta G, Miller AB, et al. Long-term disease-specific functioning among prostate cancer survivors and noncancer controls in the prostate, lung, colorectal, and ovarian cancer screening trial. J Clin Oncol 2012;30(22):2768-75.
3.American Cancer Society. Cancer treatment & survivorship facts & figures 2016-2017. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/cancer-treatment-and-survivorship-facts-and-figures/cancer-treatment-and-survivorship-facts-and-figures-2016-2017.pdf. Accessed 10-24-2018.
4.Green CR, Hart-Johnson T, Loeffler DR. Cancer-related chronic pain: examining quality of life in diverse cancer survivors. Cancer 2011;117(9):1994-2003.
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