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BPH and Prostate Cancer (FL INITIAL Autonomous Practice - Differential Diagnosis)

4 Contact Hours
Only FL APRNs will receive credit for this course.
This course is only applicable for Florida nurse practitioners who need to meet the autonomous practice initial licensure requirement.
This peer reviewed course is applicable for the following professions:
Advanced Practice Registered Nurse (APRN)
This course will be updated or discontinued on or before Monday, February 20, 2023

Nationally Accredited

CEUFast, Inc. is accredited as a provider of nursing continuing professional development by the American Nurses Credentialing Center's Commission on Accreditation. ANCC Provider number #P0274.


Outcomes

The purpose of this course is for participants to understand the pathophysiology, common clinical presentation, and treatment options for BPH and Prostate Cancer.

Objectives

After completing this course, the learner will be able to meet the following objectives:

  1. List two symptoms that are not common symptoms of BPH.
  2. Define the American Urologic Association Symptom Index tool.
  3. Name the alpha-adrenergic agonists that are no longer used to treat BPH.
  4. Identify the most common location where prostate cancer occurs.
  5. Discuss drug approval for the prevention of prostate cancer.
CEUFast Inc. and the course planners for this educational activity do not have any relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.

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Author:    Berthina Coleman (MD, BSN,RN)

Benign Prostatic Hyperplasia

The prostate gland is located in the pelvis anterior to the rectum and inferior posterior to the bladder. The prostate gland comprises stromal, neuroendocrine, and epithelial cells. The gland is surrounded by periprostatic and dorsal venous systems and

neurovascular bundles, which help maintain erectile function. The periurethral part of the prostate gland increases in size during puberty and after the age of 55 due to the nonmalignant growth of cells in the transition zone of the prostate gland, which surrounds the prostatic urethra. Prostate-specific antigen (PSA) and prostatic acid phosphatase are produced by epithelial cells in the prostate gland (Scher et al., nd). The prostate gland contains alpha-reductase, which converts testosterone to dihydrotestosterone (Scher et al., nd).

Benign prostatic hyperplasia (BPH) is a disease process that causes lower urinary tract signs and symptoms. Several factors can clue clinicians into a diagnosis of BPH, namely: enlarged prostate on examination, irritative or obstructive symptoms on voiding, and an increased American Urologic Association Score Index (AUASI). THE ASSESSMENT OF the AUASI score is further discussed in the "Diagnosing BPH" section. Data from autopsies showed that the prevalence of BPH approaches 50% by age 60 and 90% by age 80 (Scher et al., nd). Older men affected with BPH tend to underreport their findings of BPH and may remain untreated for long periods. In addition, other diagnoses must be excluded, such as urinary tract infection and prostatitis.

Clinical Manifestations of BPH

Lower urinary tract symptoms are divided into 2 main groups: irritative or obstructive symptoms. Irritative symptoms include urinary urgency, urge incontinence, nocturia, and urinary frequency. Obstructive symptoms include straining, dribbling, prolonged voiding, urinary hesitancy, and a weak urine stream. Most of the symptoms associated with BPH occur due to gland enlargement. Still, detrusor dysfunction seen in older patients has also been implicated as a cause of lower urinary tract symptoms.

Other symptoms of BPH include nocturia and incomplete bladder emptying. Note that hematuria and dysuria are not common symptoms of BPH and should alert clinicians that a more sinister diagnosis such as prostate cancer or transitional cell cancer must be considered.

Diagnosing BPH

Primary care clinicians have the difficult task of balancing the benefits of diagnostic and treatment interventions versus the effects these interventions will have on the patient's quality of life.

The American Urological Association Symptom Index (AUASI)

This is a diagnostic tool that clinicians can use to screen patients for symptoms of BPH. It is a 7-item tool with individual item scores ranging from 0 to 5. Zero corresponds with an assessment of "not at all." A corresponds to "almost always." The maximum score possible using this tool is a 35, and it allows clinicians to assess the severity of the patient's symptoms. The American Urological Association developed a symptom index (AUASI) adopted on the international scale as the International Prostate Symptom Score (IPSS). Patients are usually assessed using the AUASI scale at fixed intervals as they undergo different types of therapy, and the score is used to evaluate treatment response.

Digital Rectal Examination in Patients with BPH

The prostate gland is usually enlarged and rubbery in patients with BPH on palpation. Digital rectal examination is not sensitive for detecting BPH, with up to 52% of cases being missed. Note that the size of the prostate gland does not correlate with the severity of the patient's symptoms. If the enlarged prostate gland does cause urinary obstruction symptoms, patients may present with a distended bladder which can be palpated on physical examination of the abdomen.

Based on the American Urological Association recommendations, patients who present with an enlarged prostate also get a screening prostate-specific antigen (PSA) level to screen for prostate cancer. PSA levels greater than 4 ng/mL are suspicious for prostate cancer, and these patients need further workup with laboratory tests, diagnostic imaging, and cystoscopy. In men over the age of 60, a PSA level above 2 ng/mL has been shown to correlate with prostate volumes greater than 40 mL. However, not all patients with an elevated PSA level have BPH or prostate cancer. Patients with prostatitis and indwelling Foley catheters may also have an elevated PSA.

Diagnostic Imaging for the Diagnosis of BPH

Prostate volume can be evaluated by a transrectal or transabdominal ultrasound. There are no current recommendations for routine use of diagnostic imaging to evaluate BPH. Bladder ultrasound can be used to assess bladder post void residues. Patients can be identified for intervention if bladder post void residues remain high. Uroflowmetry can measure Urine flow rates to identify patients who require intervention. Urodynamic studies focus on detecting primary bladder dysfunction.

Patients with hematuria require cystoscopy, which directly visualizes the urine outflow tract before surgery. Cross-sectional imaging (CT, ultrasound) is required for patients with a history of previous urinary tract dysfunction such as calculi or hematuria. Most patients diagnosed with benign prostatic hyperplasia present to the clinicians for symptom relief.

Differential Diagnosis

Patients who present with lower urinary tract symptoms require a detailed history to identify patient habits that may potentiate patient symptoms. For example, nighttime drinking habits may cause symptoms of nocturia. Medications such as Lasix at bedtime may also affect symptoms of nocturia. Voiding diaries record patients keep detailing what types of beverages they drink throughout the day. The patients in their voiding record also document exact volumes and specific times.

Certain over-the-counter medications can lead to symptoms of urinary retention, such as diphenhydramine, an anticholinergic. Other medical conditions can also be mistaken for symptoms of BPH. For example, diabetes mellitus can present as polyphagia, polydipsia, and polyuria. Polyuria may be mistaken for a symptom of BPH, but it should resolve once the diabetes mellitus is controlled (Scher et al., nd).

If a patient presents with radiculopathy, back pain, and anorexia symptoms, clinicians should be concerned about prostate cancer and associated metastatic disease. Pain on ejaculation and pain on palpation are both symptoms of prostatitis. These patients should have a urinalysis performed, which shows leukocytosis and positive nitrites. Nephrolithiasis is characterized by hematuria and or flank pain.

Complications

If not treated, Bladder outlet obstruction will lead to acute renal injury, recurrent urinary tract infections, and eventually chronic kidney disease. Approximately 20% of patients with BPH present with acute bladder outlet obstruction.

Treatment of BPH

In general, asymptomatic patients are not treated regardless of the size of the prostate gland. On the contrary, patients who present with serious and debilitating symptoms such as gross hematuria, recurrent infection, inability to urinate, and the presence of stones may require surgery (Scher et al., nd).

The severity of the patient's symptoms at presentation determines treatment interventions. The severity of the patient's symptoms is determined using the patient's AUASI score. Mild severity implies an AUASI score less than or equal to 7. These patients should be educated on implementing strategies that will help minimize symptoms, such as eliminating fluid intake at bedtime, avoiding caffeine intake, and reducing alcohol consumption. Patients with mild symptoms usually do not require treatment with medications and should be monitored closely if their symptoms worsen.

Patients with moderate to severe symptoms usually have an AUASI score between 7 and 19. Patients with an AUASI score between 20 and 35 are considered severe. These patients with moderate and severe symptoms have clinically significant symptoms warranting medical treatment.

Medical Therapy for Benign Prostatic Hyperplasia

Alpha-adrenergic receptor antagonists such as tamsulosin are first-line treatments for BPH. They work by decreasing the sympathetic action at the bladder outlet allowing for easier excretion of urine. Certain alpha-antagonists such as terazosin, prazosin, and doxazosin appear on the 2015 Beers Criteria for medications that should be used with caution in older patients due to the risk of orthostatic hypotension (AGS, 2015). However, this refers to their use as antihypertensives. When starting alpha-1 adrenergic antagonists, it is important to begin with, the lowest possible dose and titrate up as needed. Note that prazosin is not recommended for treating BPH-related symptoms due to the high incidence of side effects. Note that alpha-adrenergic antagonists must not be initiated before planned cataracts surgery due to the association of their use with intraoperative floppy iris syndrome noted during cataracts surgery; of all alpha-1 adrenergic antagonists, tamsulosin is the most frequently implicated. If a patient is already on tamsulosin, there is no clear evidence that stopping the medication before cataract surgery will prevent the occurrence of intraoperative floppy iris syndrome.

5-alpha reductase inhibitors work by decreasing prostatic volume, which ultimately alleviates symptoms of BPH, although they work much slower than alpha-adrenergic antagonists. Occasionally, both drug classes will be used in a combination regimen. 5-alpha reductase inhibitors work by delaying disease progression in patients with BPH. They are particularly useful in preventing episodes of acute urinary retention and eventually alleviating the need for surgery. 5-alpha reductase inhibitors are more efficient in patients with a significantly enlarged prostate, as determined on physical examination. Drugs in this class are less effective at alleviating lower urinary tract symptoms than alpha-adrenergic inhibitors. Examples of medications in this drug class include dutasteride and finasteride. Note that dutasteride is associated with longer side effects due to its long half-life of approximately 5 weeks. Dutasteride's side effects include decreased libido, impotence, breast tenderness, and enlargement. Finasteride can only be administered in patients who swallow whole pills because it cannot be crushed.

Combination therapy using 5-alpha reductase inhibitors and alpha-adrenergic inhibitors work more effectively than either drug class by itself. Currently, finasteride and doxazosin are used in combination, while dutasteride and tamsulosin are used in combination.

Phosphodiesterase inhibitors are currently used in the treatment of erectile dysfunction and have been shown to improve BPH symptoms. There are 4 phosphodiesterase inhibitors presently used in the United States, and they all appear to work effectively in reducing the symptoms of BPH; namely, sildenafil (Viagra®), vardenafil (Levitra®), tadalafil (Cialis®), and avanafil (Stendra®). A common side effect of phosphodiesterase inhibitors is hypotension which is also a side effect of alpha-adrenergic antagonists; therefore, patients must be warned about the potentiation of hypotension, and drug dosing should be carefully monitored

There are several alternative medicine options and over-the-counter medications used to treat symptoms of BPH. Examples include saw palmetto and stinging nettle. There is little evidence documenting their efficacy.

It is not usual for symptoms of BPH to occur concurrently with symptoms of overactive bladder. The most common medication class used to treat overactive bladder is anticholinergics such as Oxybutynin (Ditropan® XL, Oxytrol®) and Tolterodine (Detrol®).

Surgical Interventions for BPH

Surgical therapy is used as second-line therapy for BPH, and it is usually considered in patients who have failed primary treatment with medication. Patients with persistent lower urinary tract symptoms who fail medication therapy may require surgery. Any patients with BPH-related renal failure also meet the criteria for surgical interventions. (Scher et al., nd).

Surgical therapy focuses on reducing the prostate gland's size and removing any obstruction to urine flow. Several surgical approaches are used in practice, with the most common procedures being transurethral resection of the prostate (TURP) and transurethral incision of the prostate (TUIP). Other prostatectomy approaches can be perineal, retropubic, or suprapubic. Transurethral ultrasound-guided laser-induced prostatectomy (TULIP) is a surgical approach also used in specialized centers. The choice of surgical approach is dependent upon the size of the prostate gland, surrounding anatomy, patient comorbidities, and technical skill of the surgeon (Scher et al., nd).

Prostate Cancer

In 2017, 26,730 patients died from prostate cancer in the United States (Scher et al., nd). Approximately 161,000 men were diagnosed with prostate cancer. Over the past decade, the total number of men dying from prostate cancer has decreased. This decline in prostate cancer-related deaths has been linked to the ubiquitous use of PSA detection screening strategies. In the United States, 1 in 6 men will be diagnosed with prostate cancer in their lifetime, making it the second leading cause of cancer deaths among men (Scher et al., nd). Out of every 30 men diagnosed with prostate cancer will die from the disease (Scher et al., nd).

Autopsies of men in their 80's have shown that up to 70% of all patients surveyed had malignant changes in their prostate. At the same time, more than 90% of patients had hyperplastic changes in their prostate gland (Scher et al., nd). Given that elderly patients are at increased risk for adverse effects based on concomitant comorbidities, the diagnosis and treatment of prostate cancer must be adapted to the risk imposed on the patient.

More than 2 million men in the United States live with prostate cancer. Morbidity and mortality from prostate cancer increase linearly with age. According to the Surveillance Epidemiology and End Results, data gathered between 2005 – 2009, 58% of men diagnosed with prostate cancer were 65 years or older. 90% of men who died from prostate cancer were over 65 years or older (Scher et al., nd). Currently, the 5-year prostate cancer survival rate is approximately 99% raising more questions about the value of over screening men with an average risk for prostate cancer. Most prostate cancers occur in the peripheral zone, and these cancers can be assessed on physical examination during a digital rectal exam (Scher et al., nd).

Risks factors for Prostate Cancer

Prostate cancer can be hereditary; there is a five-fold increased risk of the disease if two or more relatives are affected. There is an increased risk in patients with hereditary prostate cancer (HPC 1) gene locus. Certain dietary and environmental factors affect the growth and progression of prostate cancer (Pritchard et al., 2016). A high intake of dietary fats and aromatic hydrocarbons is believed to increase the risk of prostate cancer (Bilen & Corn, nd). The risk of prostate cancer in Asian men increases when they move to the west and adopt a western lifestyle (Scher et al., nd).

A few dietary factors are considered protective against prostate cancer, such as lycopene found in tomatoes isothiocyanate sulforaphane seen in cruciferous vegetables (Scher et al., nd). The use of statins and their role in inhibiting cholesterol biosynthesis has also been characterized as a protective factor.

Most prostate cancers develop adjacent to a lesion known as proliferative inflammatory atrophy, which suggests a role for inflammation in the pathogenesis of prostate cancer (Bilen & Corn, nd). Abstaining from smoking, regular exercise, and maintaining a regular body weight may reduce the risk of progression.

Diagnosis and Treatment of Prostate Cancer

To minimize the overdiagnosis of clinically insignificant disease, patient risk factors and clinical presentations are carefully considered. Clinically important questions to answer include is there a biopsy-proven cancer present?; Is there any metastatic disease or regional spread based on imaging studies? What is the testosterone level? Every time the patient is assessed, a decision must be made regarding the benefits and risks of treatment instead of leaving the disease untreated.

In general, the greater the disease burden, the greater the need for treatment. Patients who already have a cancer diagnosis must carefully consider the adverse effects of treatment based on the patient's life expectancy (Bilen & Corn, nd).

Many patients with prostate cancer may opt for cancer control which puts the patient in a category where the disease is determined to be extremely slowed down to the point where it is deemed unlikely to metastasize or shorten the patient's life expectancy. This is in contradistinction to disease cure, which focuses on eliminating all cancer cells. From the patient's perspective, both outcomes are considered equivalent since they do not experience any disease symptoms in both scenarios. When disease recurrence is documented, the implementation of an intervention is based on the rate of disease spread and the risk-to-benefit ratio of the intervention being considered.

Prostate Cancer Prevention

Currently, there is no agent approved for the prevention of prostate cancer. Several trials have been conducted to evaluate the reduction in the future risk of a prostate cancer diagnosis with different agents. For example, in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, a decrease in the incidence of prostate cancer from 25% with placebo to 20% with a Dutasteride was noted (Bilen & Corn, nd). The Prostate Cancer Prevention Trial showed a reduction in the incidence of prostate cancer from 24% with placebo to 18% with finasteride (Bilen & Corn, nd). However, most studies reported that most cancers prevented were low-risk cancers. Despite the trials, no drug has been approved to prevent prostate cancer. Vitamin E, Vitamin C, and Selenium have also been studied to treat prostate cancer but have not shown any benefit compared to placebos.

Screening and Early Detection of Prostate Cancer

The diagnosis of prostate cancer must be balanced against the benefit of detecting and treating clinically significant cancers that will negatively affect the patient's quality of life if left untreated. It is important to not over-diagnose and over-treat clinically insignificant cancers. The decision to pursue prostate cancer diagnosis and or treatment is best made as a shared decision between the patient and their physician. Multiple factors warrant the decision to pursue a prostate cancer diagnosis, including an elevated serum PSA, abnormal digital rectal examination, and genetic risk factors (Bilen & Corn, nd). History taking should focus on outlet obstruction symptoms, incontinence, change in ejaculatory pattern, and potency.

Physical Examination

The digital rectal examination focuses on the prostate size and consistency within the prostate gland. Most prostate cancers occur in the peripheral zone and are palpated on digital rectal examination (Scher et al., nd). In general, carcinomas are irregular, hard, with or without induration caused by benign prostatic hyperplasia.

Prostate Specific Antigen

Prostate-specific antigen was initially approved by the United States Food and Drug Administration in 1994 for early detection of prostate cancer (Buyyoungouski et al., 2017). The ubiquitous use of the test has had a significant role in diagnosing men with early-stage prostate cancers. Up to 80% of newly diagnosed cancers are confined to the organ at diagnosis. The PSA level is strongly associated with the disease extent and disease outcome. A single measurement of PSA at age 60 has a balanced sensitivity and specificity of approximately 0.9 (on a scale from 1-10). Despite this data, the routine use of PSA levels for screening remains controversial.

The United States Preventive Services Task Force published a review in 2017 about the evidence for PSA based screening for prostate cancer; they made a recommendation of a "C" on screening for prostate cancer using PSA levels in patients between the ages of 55 and 99 The USPSTF recommendation of a "C" means that providing this service to individual patients based on professional judgment and patient preferences may provide a small benefit. The USPSTF also recommends that men above 70 should not be screened using PSA levels (Thrasher, 2018).

The American Urological Association maintains that the benefits of screening for prostate cancer using PSA levels are moderate for men between the ages of 55 and 69 years of age. Men outside of this age group have not been shown to benefit from screening; rather, it has been shown that they may be harmed by overdiagnosis and overtreatment (Thrasher, 2018). As of 2013, the American Urological Association does not recommend that men outside this age group be screened (Thrasher, 2018).

The USPSTF recognizes that the increased use of active surveillance when managing prostate cancer patients with low-risk cancers have reduced the risks associated with increased screening for prostate cancer. Active surveillance is defined as observation with selective delayed treatment for low-risk prostate cancers (Thrasher, 2018).

Scher and Eastham proposed some basic steps to implement when screening patients with prostate cancer (Scher et al., nd):

  • Avoid PSA screening in men who have little to gain from screening, such as asymptomatic patients or patients who have a very short life expectancy.
  • Men over the age of 75 should not be tested unless they are in excellent overall health or had a higher than average PSA measured before 70.
  • Baseline PSA is a strong predictor of the future incidence of lethal prostate cancer. For example, men with low PSAs, less than 1 ng/mL, can undergo less frequent PSA testing as infrequent as once every 5 years. In addition, if the PSA remains less than 1 ng/mL, clinicians should consider ending screening at age 60.
  • Men with above-average PSA, which does not warrant obtaining a prostate biopsy, should be instructed and encouraged to return for annual screening regularly.
  • Patients with prostate cancer who do not need treatment should never be treated as the risks may outweigh the benefits. A significant amount of men diagnosed with prostate cancer do not need immediate treatment but instead can be managed with active surveillance.
  • Patients with prostate cancer who do not meet the criteria for immediate treatment should be referred to tertiary high-volume centers so that high volume providers can manage them to improve control of the primary cancer and decrease complications from cancer treatment strategies.

A total PSA level greater than 4 ng/mL is frequently used as a threshold for a prostate biopsy. However, most men with elevated PSA based on this criterion do not have prostate cancer at the time of biopsy. Conversely, many men with PSA levels below 4 ng/mL have cancerous cells in their prostate glands (Buyyoungouski et al., 2017). The Prostate Cancer Prevention Trial demonstrates no PSA level below which the risk of prostate cancer is completely removed or becomes zero.

Prostate screening has the challenge of increasing the test's sensitivity in detecting younger men who are more likely to die of the disease while reducing the detection of low-grade cancers in older men who are more likely to die from other causes (Barry & Simmons, 2017). Patients diagnosed with prostatitis must be treated before biopsy, but patients with an elevated PSA should not be automatically treated with antibiotics, especially if asymptomatic.

Other Screening Tests for Prostate Cancer

There are second-line screening tests for prostate cancer, such as the 4K Score Test, which measures 4 prostate-specific kallikreins; namely, free PSA, intact PSA, total PSA, and human kallikrein. The 4K score test has been used to estimate a patient's risk of having prostate cancer and the chance that the tumor found will be a high-grade tumor. The 4K Score Test is performed by Opko laboratory in Nashville, TN (Scher et al., nd). The Innovative Diagnostic Laboratory performs the Prostate Health Index (PHI) in Richmond, VA. It estimates the risk of having prostate cancer by combining the Free PSA, total PSA, and the pro PSA isoform of free PSA. Together, these tests are used to calculate the PHI score. The PHI is more accurate than free PSA alone or total PSA alone (Scher et al., nd).

Prostate Biopsy

Most prostate biopsies are performed under image guidance; transrectal ultrasound, Magnetic Resonance Imaging (MRI), or a combination of the two modalities can be used to ascertain that all the prostate gland's suspicious areas are appropriately identified sampled. Most prostate biopsies include 12 samples from the peripheral zone and suspicious areas in the gland either by palpation or direct visualization (Barry & Simmons, 2017). Patients with a negative prostate biopsy may require additional testing, including a repeat biopsy, PHI testing, or 4K Score testing.

Pathology

95% of prostate cancers diagnosed are adenocarcinomas. Squamous, transitional cells and carcinosarcomas make up about 5% of all tumors diagnosed. Metastatic disease to the prostate gland is very rare; occasionally, there is a direct invasion of the prostate gland by adjacent tumors from the bladder and rectum.

Gleason Grading System

The Gleason grading system is used to measure the histologic aggressiveness of the tumor. In general, patients are given Gleason grades, the primary grade describes the cells in the largest part of the tumor, and the secondary grade describes the cells in the next largest part of the tumor (Martin, nd). The total Gleason score combines the primary and secondary grades. Dominant and secondary histologic patterns are scored with a total score of 2 -10, with 10 being the worst score (Martin, nd). The most poorly differentiated area of the tumor will determine the overall biological behavior of the tumor. Other specific factors documented are the presence or absence of extracapsular spread and perineural invasion. In most modern practices, Gleason scores less than 6 are never assigned, and Gleason's score of 6 denotes a favorable outcome. However, because the Gleason score range has not been adjusted to reflect this practice change, this became a source of confusion for patients who believe that a tumor with a Gleason score of 6 on a scale of 2 - 10 implied that the tumor is of moderate grade. To clarify this confusion, a 5-grade system has been created (Martin, nd).:

  • Grade 1: Gleason score less than or equal to 6.
  • Grade 2: Gleason score 3 + 4 = 7. The first digit represents the primary grade, and the second represents the secondary grade.
  • Grade 3: Gleason score 4 + 3 = 7.
  • Grade 4: Gleason score 4 + 4 = 8.
  • Grade 5: Gleason scores 9 and 10.

Based on this system, the lowest risk group is Group 1, and this grading system has been accurately shown to predict prognosis (Martin, nd).

Prostate Cancer Staging

Prostate cancer staging is based on the TNM (tumor size, nodes, and metastases) system. Tumors identified only based on an abnormal PSA are generally T1 tumors. Tumors that are palpable but remain confined to the prostate gland are T2 tumors. T3 tumor extends past the prostate capsule and may invade the seminal vesicle. T4 tumors extend outside the gland and invade other adjacent structures (Barry & Simmons, 2017). Clinicians must not rely on digital rectal examination alone to assess the extent of the disease within and outside of the gland. Given the limitations of digital rectal examination, imaging has become an integral part in accurately staging the patient's extent of disease. Note that 80% of patients with prostate cancer present with local disease meaning T1 or T2 disease. Local disease at presentation is associated with a 5-year survival rate of 100% (Buyyoungouski et al., 2017). 12% of patients with prostate cancer present with a regional disease, which is defined as T3 or T4 disease without evidence of metastases which has also been shown to have a 100% 5-year survival rate. 4% of patients present with a distant disease which is T4 disease, present with metastases, and have an associated 5-year survival rate of 30% (Barry & Simmons, 2017).

According to the American Joint Committee on Cancer, the transrectal ultrasound is the imaging modality most commonly used in prostate biopsies. MRI is the most useful modality in detecting extraprostatic extension compared to computed tomography (CT). Overall, MRI is the most useful modality for prostate cancer staging and has also been valuable in surgical planning (Buyyoungouski et al., 2017). Nuclear medicine bone scans are also commonly used to evaluate metastatic to the bones (Gartrell et al., 2015).

Treatment of Prostate Cancer

Patients with clinically localized diseases are usually treated with active surveillance, radical prostatectomy, and radiation therapy. The choice of therapy is based on the probability that the untreated tumor will adversely affect patient survival and quality of life (Barry & Simmons, 2017). PSA relapse-free survival is commonly used because metastatic progression on examination or imaging may not be apparent for years. After radical prostatectomy, PSA usually becomes undetectable in the blood within 6 weeks, and if that does not occur, the patient is considered to have a residual or recurrent disease (Buyyoungouski et al., 2017). Extensive local disease increases the probability of regional lymph node extension even when they appear normal on imaging.

Several factors can help guide treatment in addition to the initial clinical T stage, including the number of biopsy cores in which cancer is detected, the biopsy Gleason score, and the baseline PSA. Other clinical practices focus on final cut-off points to determine treatment modalities, such as a Gleason score of 8 and above PSA greater than 10 ng/mL.

Prostate cancer treatment modalities can be associated with significant adverse effects. In patients who undergo a radical prostatectomy, incontinence rates can be as high as 47%, while impotence rates range from 25 - 89%. Note that with radical prostatectomy, impotence may be immediate but resolve over time. In patients who receive radiation therapy, impotence is not immediate but may develop over a long time, possibly over months (Gartrell et al., 2015). Note that bowel function can also be adversely affected by radical prostatectomy.

Radical Prostatectomy

The primary purpose of radical prostatectomy is to remove cancer with clear margins while avoiding the external urethral sphincter and sparing the autonomic nerves in the neurovascular bundles that control potency. Radical prostatectomy is usually performed in patients with a life expectancy of more than 10 years. It can be performed through a perineal or retropubic approach (Buyyoungouski et al., 2017). Minimally invasive approaches have been linked to shorter hospital stays.

Neoadjuvant hormonal treatment with gonadotropin-releasing hormone (GnRH) agonists/antagonists. Several large trials had shown that a few months of androgen depletion before surgery led to serum PSA levels decreasing by 96% with a concurrent decrease in the volume of the prostate gland itself (James et al., 2017). This was also linked to a decrease in positive margins from 41% to 17%. However, these specific metrics have not been shown to improve PSA-free survival in patients with prostate cancer.

Factors linked to incontinence in patients who undergo a radical prostatectomy include urethral length, older age, and the surgeon's skill operating.

Recovery of erectile function after radical prostatectomy is associated with better quality of erections before surgery, younger age, and failure to damage the neurovascular bundles. On average, the erectile function returns about 6 months after surgery, provided that the neurovascular bundles are preserved. If one of the neurovascular bundles is affected, the patient's potency is reduced by 50% (Scher et al., nd). However, most patients recover satisfactory sexual function with the use of intraurethral inserts, phosphodiesterase inhibitors, or intracavernosal injections (Barry & Simmons, 2017).

Radiation Therapy

Radiation therapy is usually administered by external beam therapy or the radioactive source implanted into the gland. External beam radiation therapy focuses on delivering high doses to the prostate while reducing exposure to the surrounding tissues (Thrasher, 2018). Advances in technology have permitted the safe delivery of radiation doses higher than 80 Gy, allowing for greater local disease control rates and fewer side effects (Thrasher, 2018). After cancer control has been achieved using radiation therapy, biochemical failure is defined as a rise in PSA by more than 2 ng/mL higher than the lowest PSA achieved (Scher et al., nd) Fractionating radiation doses and minimizing the use of multiple high radiation dose treatments have been shown to improve cancer control rates while reducing treatment-related morbidity. In some cases, radiation doses can be fractionated in as many as 26 treatments or as few as 5 treatments (Scher et al., nd)

Androgen deprivation therapy has been used in combination with radiation to improve overall patient survival, especially in high-risk diseases. The purpose of administering hormone therapy before radiation therapy is to decrease the prostate's size to limit exposure of the normal prostate gland to radiation therapy (James et al., 2017). Using hormone therapy before radiation therapy on patient survival remains unclear. Prostatectomy has increased urinary incontinence and loss of sexual function (James et al., 2017). Bowel function was worse in the radiotherapy group than in the other treatment modalities.

Brachytherapy

This is the implantation of radioactive seeds into the prostate gland (Scher et al., nd). The goal of brachytherapy is to maximize radiation delivery to the prostate gland while minimizing the radiation of surrounding tissues. The brachytherapy seeds are placed with the assistance of imaging. The implantation is done through a transperineal approach. Most patients tolerate brachytherapy well, with a few patients reporting symptoms of urinary urgency and frequency which can take months to resolve. Patients who have had prior transurethral resection of the prostate tend to have higher rates of complications (Scher et al., nd).

Active Surveillance

Most patients diagnosed with prostate cancer in the United States present with early-stage disease (Scher et al., nd). In these cases, active surveillance is recommended. Active surveillance was previously called deferred therapy or watchful waiting. In general, it is recommended in patients with non-aggressive tumors. These patients are usually monitored at intervals via PSA measurements, imaging with prostate MRI protocols, and digital rectal examinations. These patients are followed with repeat prostate biopsies as indicated based on serologic and imaging findings until disease progression necessitates treatment with curative intent.

The challenge with active surveillance is predicting pathology despite multiple core biopsies being obtained. In addition, the multifocal disease can make active surveillance challenging. Finally, clinicians may miss an opportunity to cure the disease when the tumor is surveilled. There is continued research into identifying patients best treated by active surveillance.

Patients with Rising PSA After Surgery or Radiation Therapy

Some patients present with a rising PSA as the only manifestation of prostate cancer disease (Scher et al., nd). In these patients, the main issue is determining whether the disease is local or systemic, given that management is quite different for each situation. Disease limited to the primary site is typically treated with additional local therapy. After prostatectomy, a recommendation for radiation therapy is usually guided by the pathologic findings and the imaging findings, MRI of the prostate. Some clinicians recommend that a biopsy of the urethrovesical anastomosis be performed before deciding about radiation therapy. Gallium and Fluorine Positron emission tomography (PET) are commonly used to detect small disease foci in the surgical bed or more distant sites.

Metastatic Disease in a Non-castrated Patient

Non-castrate metastatic disease refers to men with levels of testosterone greater than 150 ng/dL who present with metastatic disease (Scher et al., nd). Symptoms of metastatic disease include pain from the disease in the bones, spinal cord compression, coagulopathy, or completely asymptomatic patients. Testosterone lowering drugs include GnRH agonists/antagonists, estrogens, and CYP 17 inhibitors. Estrogens have been linked to increased risk of strokes, embolic phenomenon, and phlebitis; they are now used sparingly in clinical practice. These drugs all work to produce chemical castration (Fizazi et al., 2017).

Castration-Resistant Prostate Cancer

Castration-resistant prostate cancer is defined as a disease that progresses while the testosterone levels are equal to or lower than 50 ng/dL (Fizazi et al., 2017). A disease that progresses with low testosterone levels tends to be lethal for most men. It typically presents metastatic disease to the bones combined with a rising PSA level. In such patients, it is important to define therapeutic goals. For example, pain relief may be more important than lowering PSA levels. Overall, the main goal is to delay disease progression or new symptom development. Visceral and nodal metastatic disease is rarely seen in this patient group.

Pain Control

Pain from bony metastases is one of the greatest contributors to patient morbidity. It is typically managed with large amounts of narcotics which further affects patient morbidity. Neurologic symptoms secondary to cord compression or foraminal narrowing may require urgent/emergent intervention (Gartrell et al., 2015). Focal bone pain is best treated with external beam radiation, while diffuse disease sites in the absence of neurologic symptoms are usually treated with radioisotope therapy such as Radium. Bisphosphonate use is associated with decreased frequency and severity of bone complications. Note that regression in the bone-related complications does not necessarily imply a decrease in the PSA levels.

Case Study

You are a nurse on the floor taking care of a patient who is now on post-operative day 1 from transurethral resection of the prostate (TURP). The patient has a Foley catheter and requires continuous bladder irrigation to prevent blood clot formation. Discuss why the patient requires continuous bladder irrigation and how the patient's care should be performed.

Discussion

After a TURP procedure, blood clots form copiously in the bladder putting the patient at increased risk of developing acute urinary retention. Significant blood loss can occur due to blood clots forming in the bladder. When performing bladder irrigation, a large three-way irrigation catheter is used. Large catheters with sizes between 22F to 26F are used. Normal saline irrigation fluid is continuously allowed to flow into the bladder while allowing bladder debris and blood clots to free outflow.

This process is continued until the bleeding stops or the bladder becomes decompressed. In general, fluid flows out of the bladder by gravity. However, irrigation can be performed by gentle flushing using a 60-cc syringe. Irrigation can be as brisk as 2 L per hour, provided that the volume of fluid put into the bladder equals the fluid draining out. During bladder irrigation and at the end of the procedure, the goal is to maintain clear urine.

Conclusion

Benign prostatic hyperplasia and prostate cancer are diseases that usually affect elderly patients. With BPH, treatment is dictated by controlling symptoms with medical interventions considered before surgical interventions. In patients with prostate cancer, treatment decisions are made under 2 main paradigms: disease control and cure. The decision is made with the patient's input keeping in mind their quality of life and expected life expectancy. Physicians, nurses, and other clinical providers are responsible for empowering patients in making decisions regarding treatment options, including the decision not to pursue any treatment.

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References

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