Prostate Carcinoma - Clinicals, Diagnosis, and Management

Urology

Clinicals - History

Fact Explanation
Hesitancy (difficulty initiating the stream) , poor and/or intermittent stream, straining, prolonged micturition, feeling of incomplete bladder emptying, dribbling Voiding or obstructive type of lower urinary tract symptoms (LUTS) due to bladder outflow obstruction caused by enlarged prostate Hesitancy (difficulty initiating the stream) , poor and/or intermittent stream, straining, prolonged micturition, feeling of incomplete bladder emptying, dribbling
Voiding or obstructive type of lower urinary tract symptoms (LUTS) due to bladder outflow obstruction caused by enlarged prostate
Frequency, urgency (compelling need to void that cannot be deferred), urge incontinence (sudden and strong need to urinate which cannot be controlled) and nocturia (voiding at night) Storage or irritative symptoms of LUTS due to secondary detrusor instability causing an overactive bladder Frequency, urgency (compelling need to void that cannot be deferred), urge incontinence (sudden and strong need to urinate which cannot be controlled) and nocturia (voiding at night)
Storage or irritative symptoms of LUTS due to secondary detrusor instability causing an overactive bladder
Hematuria Gross hematuria / microscopic hematuria can be a result of cancer itself, a side effect of previous treatments (acute or chronic toxicity of radiotherapy, stone formation on a suture after surgery) Hematuria
Gross hematuria / microscopic hematuria can be a result of cancer itself, a side effect of previous treatments (acute or chronic toxicity of radiotherapy, stone formation on a suture after surgery)
Progressive back pain Prostate can be spread to bones ( lumbar vertebrae through venous plexus, hip/ pelvic bones) . Back pain occur due to bone metastasis Progressive back pain
Prostate can be spread to bones ( lumbar vertebrae through venous plexus, hip/ pelvic bones) . Back pain occur due to bone metastasis
Numbness of feet Lower extremity neurologic impairment can occur due to bone metastasis Numbness of feet
Lower extremity neurologic impairment can occur due to bone metastasis
Old age Prostate cancer is very rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50. About 6 in 10 cases of prostate cancer are found in men over the age of 65 Old age
Prostate cancer is very rare in men younger than 40, but the chance of having prostate cancer rises rapidly after age 50. About 6 in 10 cases of prostate cancer are found in men over the age of 65
Family history of prostate cancer Prostate cancer seems to run in some families, which suggests that in some cases there may be an inherited or genetic factor.
Some inherited gene changes raise the risk for more than one type of cancer. For example, inherited mutations of the BRCA1 or BRCA2 genes are the reason that breast and ovarian cancers are much more common in some families. Mutations in these genes may also increase prostate cancer risk in some men, but they account for a very small percentage of prostate cancer cases.
Family history of prostate cancer
Prostate cancer seems to run in some families, which suggests that in some cases there may be an inherited or genetic factor.
Some inherited gene changes raise the risk for more than one type of cancer. For example, inherited mutations of the BRCA1 or BRCA2 genes are the reason that breast and ovarian cancers are much more common in some families. Mutations in these genes may also increase prostate cancer risk in some men, but they account for a very small percentage of prostate cancer cases.
Incidental discovery Some countries have prostate cancer screening programmes as prostate cancer is a common cancer in men, with a lifetime prevalence of 17 percent. Prostate cancer symptoms generally occur in advanced stages, making early detection desirable. Digital rectal examination and prostate-specific antigen testing are the most commonly used screening tools.
Some patients detect the cancer incidentally due to prostatic resection for benign prostatic hyperplasia ( biopsy report)
Incidental discovery
Some countries have prostate cancer screening programmes as prostate cancer is a common cancer in men, with a lifetime prevalence of 17 percent. Prostate cancer symptoms generally occur in advanced stages, making early detection desirable. Digital rectal examination and prostate-specific antigen testing are the most commonly used screening tools.
Some patients detect the cancer incidentally due to prostatic resection for benign prostatic hyperplasia ( biopsy report)

Clinicals - Examination

Fact Explanation
Digital rectal examination Prostate is enlarged, asymmetric, nodular, or tender. A firm nodule, generalized nodularity, and asymmetry are more concerning; whereas, symmetric enlargement is common in aging men Digital rectal examination
Prostate is enlarged, asymmetric, nodular, or tender. A firm nodule, generalized nodularity, and asymmetry are more concerning; whereas, symmetric enlargement is common in aging men
Neurological examination Lower extremity neurological impairment (low power, reduced sensation) occur due to bone metastasis (Spinal cord compression caused by metastasis) Neurological examination
Lower extremity neurological impairment (low power, reduced sensation) occur due to bone metastasis (Spinal cord compression caused by metastasis)

Investigations - Diagnosis

Fact Explanation
Prostate specific antigen (PSA) PSA as a serum marker that is 70 to 80 percent sensitive for prostate cancer.However, the PSA test is not very specific, since only one third of men with an abnormal serum PSA level actually have cancer.
Low-risk: PSA < 10
Intermediate-risk: PSA 10-20
High-risk: PSA > 20
Prostate specific antigen (PSA)
PSA as a serum marker that is 70 to 80 percent sensitive for prostate cancer.However, the PSA test is not very specific, since only one third of men with an abnormal serum PSA level actually have cancer.
Low-risk: PSA < 10
Intermediate-risk: PSA 10-20
High-risk: PSA > 20
Trans rectal ultra sound scan (TRUS) To identify the prostatic enlargement, solid areas and the echogenicity.
Almost all prostate carcinomas arise in the
outer gland. The outer gland is located in
the posterior, lateral, and apical portions of
the gland. This is fortuitous, as these portions s of the gland are most easily
imaged by TRUS
Trans rectal ultra sound scan (TRUS)
To identify the prostatic enlargement, solid areas and the echogenicity.
Almost all prostate carcinomas arise in the
outer gland. The outer gland is located in
the posterior, lateral, and apical portions of
the gland. This is fortuitous, as these portions s of the gland are most easily
imaged by TRUS

Investigations - Management

Fact Explanation
alkaline phosphatase level Elevated alkaline phosphatase level due to bone metastasis alkaline phosphatase level
Elevated alkaline phosphatase level due to bone metastasis
Prostate specific antigen (PSA) PSA levels of 4 to less than 10 ng per mL, 10 to 20 ng per mL (10 to 20 mcg per L), and greater than 20 ng per mL are associated with a low, intermediate, and high risk of prostate cancer recurrence after treatment, respectively Prostate specific antigen (PSA)
PSA levels of 4 to less than 10 ng per mL, 10 to 20 ng per mL (10 to 20 mcg per L), and greater than 20 ng per mL are associated with a low, intermediate, and high risk of prostate cancer recurrence after treatment, respectively
X ray lumbar spine Plain radiographs (X-rays) demonstrate characteristic osteoblastic lesions in lumbar vertebrae due to bone metastasis X ray lumbar spine
Plain radiographs (X-rays) demonstrate characteristic osteoblastic lesions in lumbar vertebrae due to bone metastasis
Serum creatinine Serum creatinine determination to evaluate renal function as urinary obstruction can give rise to kidney damage Serum creatinine
Serum creatinine determination to evaluate renal function as urinary obstruction can give rise to kidney damage
Serum electrolytes To evaluate renal function as urinary obstruction can give rise to kidney damage Serum electrolytes
To evaluate renal function as urinary obstruction can give rise to kidney damage
transrectal ultrasonography-guided prostate biopsy The most recent guideline from the American Cancer Society recommends transrectal ultrasonography-guided prostate biopsy as a reasonable option in men with PSA levels of 4 ng per mL (4 mcg per L) or greater.

GX: cannot assess grade
G1: the tumor closely resembles normal tissue (Gleason 2–4)
G2: the tumor somewhat resembles normal tissue (Gleason 5–6)
G3–4: the tumor resembles normal tissue barely or not at all (Gleason 7–10)
transrectal ultrasonography-guided prostate biopsy
The most recent guideline from the American Cancer Society recommends transrectal ultrasonography-guided prostate biopsy as a reasonable option in men with PSA levels of 4 ng per mL (4 mcg per L) or greater.

GX: cannot assess grade
G1: the tumor closely resembles normal tissue (Gleason 2–4)
G2: the tumor somewhat resembles normal tissue (Gleason 5–6)
G3–4: the tumor resembles normal tissue barely or not at all (Gleason 7–10)
CT / MRI pelvis, PET scans / bone scans To stage the cancer ( to detect the extent of spread )
TNM staging:

TX: cannot evaluate the primary tumor
T0: no evidence of tumor
T1: tumor present, but not detectable clinically or with imaging
T1a: tumor was incidentally found in less than 5% of prostate tissue resected (for other reasons)
T1b: tumor was incidentally found in greater than 5% of prostate tissue resected
T1c: tumor was found in a needle biopsy performed due to an elevated serum PSA
T2: the tumor can be felt (palpated) on examination, but has not spread outside the prostate
T2a: the tumor is in half or less than half of one of the prostate gland's two lobes
T2b: the tumor is in more than half of one lobe, but not both
T2c: the tumor is in both lobes but within the prostatic capsule
T3: the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2)
T3a: the tumor has spread through the capsule on one or both sides
T3b: the tumor has invaded one or both seminal vesicles
T4: the tumor has invaded other nearby structures
It should be stressed that the designation "T2c" implies a tumor which is palpable in both lobes of the prostate. Tumors which are found to be bilateral on biopsy only but which are not palpable bilaterally should not be staged as T2c.

Evaluation of the regional lymph nodes ('N')
NX: cannot evaluate the regional lymph nodes
N0: there has been no spread to the regional lymph nodes
N1: there has been spread to the regional lymph nodes

Evaluation of distant metastasis ('M')
MX: cannot evaluate distant metastasis
M0: there is no distant metastasis
M1: there is distant metastasis
M1a: the cancer has spread to lymph nodes beyond the regional ones
M1b: the cancer has spread to bone
M1c: the cancer has spread to other sites (regardless of bone involvement)
CT / MRI pelvis, PET scans / bone scans
To stage the cancer ( to detect the extent of spread )
TNM staging:

TX: cannot evaluate the primary tumor
T0: no evidence of tumor
T1: tumor present, but not detectable clinically or with imaging
T1a: tumor was incidentally found in less than 5% of prostate tissue resected (for other reasons)
T1b: tumor was incidentally found in greater than 5% of prostate tissue resected
T1c: tumor was found in a needle biopsy performed due to an elevated serum PSA
T2: the tumor can be felt (palpated) on examination, but has not spread outside the prostate
T2a: the tumor is in half or less than half of one of the prostate gland's two lobes
T2b: the tumor is in more than half of one lobe, but not both
T2c: the tumor is in both lobes but within the prostatic capsule
T3: the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2)
T3a: the tumor has spread through the capsule on one or both sides
T3b: the tumor has invaded one or both seminal vesicles
T4: the tumor has invaded other nearby structures
It should be stressed that the designation "T2c" implies a tumor which is palpable in both lobes of the prostate. Tumors which are found to be bilateral on biopsy only but which are not palpable bilaterally should not be staged as T2c.

Evaluation of the regional lymph nodes ('N')
NX: cannot evaluate the regional lymph nodes
N0: there has been no spread to the regional lymph nodes
N1: there has been spread to the regional lymph nodes

Evaluation of distant metastasis ('M')
MX: cannot evaluate distant metastasis
M0: there is no distant metastasis
M1: there is distant metastasis
M1a: the cancer has spread to lymph nodes beyond the regional ones
M1b: the cancer has spread to bone
M1c: the cancer has spread to other sites (regardless of bone involvement)

Management - Supportive

Fact Explanation
Patient education Because of long-term side effects, the integration of survival outcomes with quality of life is important. One recent study used decision modeling to estimate quality-adjusted life years (QALYs) for patients with clinically localized prostate cancer. Patients with Gleason 2 to 4 cancer had a decreased number of QALYs following treatment; conversely, patients with Gleason 7 to 10 cancer had an increased number of QALYs following treatment. Outcomes for patients with Gleason 5 to 6 cancer were less clear.

Long term side effects of treatment-

Bowel dysfunction:
Estimated risk after prostatectomy (%) - 2-7
Estimated risk after external radiation therapy (%) - 0-30
Estimated risk after brachytherapy (%) - 1-10

Erectile dysfunction:
Estimated risk after prostatectomy (%) - 50-90
Estimated risk after external radiation therapy (%) - 30-85
Estimated risk after brachytherapy (%) -
∼ 20 at 2 to 3 years,
∼ 50 at 5 to 6 years

Urinary dysfunction:
Estimated risk after prostatectomy (%) - 15-60
Estimated risk after external radiation therapy (%) - 2-30
Estimated risk after brachytherapy (%) - 12-30
Patient education
Because of long-term side effects, the integration of survival outcomes with quality of life is important. One recent study used decision modeling to estimate quality-adjusted life years (QALYs) for patients with clinically localized prostate cancer. Patients with Gleason 2 to 4 cancer had a decreased number of QALYs following treatment; conversely, patients with Gleason 7 to 10 cancer had an increased number of QALYs following treatment. Outcomes for patients with Gleason 5 to 6 cancer were less clear.

Long term side effects of treatment-

Bowel dysfunction:
Estimated risk after prostatectomy (%) - 2-7
Estimated risk after external radiation therapy (%) - 0-30
Estimated risk after brachytherapy (%) - 1-10

Erectile dysfunction:
Estimated risk after prostatectomy (%) - 50-90
Estimated risk after external radiation therapy (%) - 30-85
Estimated risk after brachytherapy (%) -
∼ 20 at 2 to 3 years,
∼ 50 at 5 to 6 years

Urinary dysfunction:
Estimated risk after prostatectomy (%) - 15-60
Estimated risk after external radiation therapy (%) - 2-30
Estimated risk after brachytherapy (%) - 12-30

Management - Specific

Fact Explanation
Conservative management Conservative management, with or without androgen ablation reserved for symptomatic disease, is one option for prostate cancer patients.
Compared with an age-matched cohort of men without prostate cancer, patients with well-differentiated prostate cancer (i.e., Gleason score of 2 to 4) did not have an increased risk of death; patients with Gleason scores of 8 to 10, however, had about a two- and threefold increase in the risk of death, respectively
Conservative management
Conservative management, with or without androgen ablation reserved for symptomatic disease, is one option for prostate cancer patients.
Compared with an age-matched cohort of men without prostate cancer, patients with well-differentiated prostate cancer (i.e., Gleason score of 2 to 4) did not have an increased risk of death; patients with Gleason scores of 8 to 10, however, had about a two- and threefold increase in the risk of death, respectively
Prostatectomy Surgical removal of the prostate is an option for patients with clinically localized cancer.
Several case series have suggested that patients with early prostate cancer have a good disease-free survival rate following radical prostatectomy.
Among patients in whom cancer was detected clinically (not by PSA screening), those who underwent radical prostatectomy (RP) had fewer prostate cancer–related deaths than patients who chose watchful waiting, although this benefit was limited to patients younger than 65 years
Prostatectomy
Surgical removal of the prostate is an option for patients with clinically localized cancer.
Several case series have suggested that patients with early prostate cancer have a good disease-free survival rate following radical prostatectomy.
Among patients in whom cancer was detected clinically (not by PSA screening), those who underwent radical prostatectomy (RP) had fewer prostate cancer–related deaths than patients who chose watchful waiting, although this benefit was limited to patients younger than 65 years
External beam radiotherapy treatment (EBRT) Another treatment for patients with localized prostate cancer is external or interstitial radiation.
Conformal external beam radiation generally has replaced conventional external radiation because higher doses of radiation can be directed to the prostate with less radiation to the surrounding tissues.
Differences between radiation and radical prostatectomy were attributable to pretreatment PSA and T-stage (lead time) and biopsy Gleason score (length time). Several case series also have shown that disease-free survival following radiation is comparable with radical prostatectomy

A systematic review found that surgery and external beam radiation therapy (EBRT) were equivalent in effectiveness, especially if the baseline PSA level was greater than 10 ng per mL. EBRT is given over eight to nine weeks and is associated with more bowel adverse effects than surgery. Surgery is more difficult if cancer recurs after EBRT
External beam radiotherapy treatment (EBRT)
Another treatment for patients with localized prostate cancer is external or interstitial radiation.
Conformal external beam radiation generally has replaced conventional external radiation because higher doses of radiation can be directed to the prostate with less radiation to the surrounding tissues.
Differences between radiation and radical prostatectomy were attributable to pretreatment PSA and T-stage (lead time) and biopsy Gleason score (length time). Several case series also have shown that disease-free survival following radiation is comparable with radical prostatectomy

A systematic review found that surgery and external beam radiation therapy (EBRT) were equivalent in effectiveness, especially if the baseline PSA level was greater than 10 ng per mL. EBRT is given over eight to nine weeks and is associated with more bowel adverse effects than surgery. Surgery is more difficult if cancer recurs after EBRT
Brachytherapy The efficacy of brachytherapy is comparable with external radiation.
In patients with low-risk cancer, brachytherapy using iodine-125 or palladium-103 pellet implantation is recommended as monotherapy. It is a preferred option in these patients because it controls the cancer as effectively as surgery or EBRT, and patients experience much less urinary incontinence and erectile dysfunction.
Brachytherapy
The efficacy of brachytherapy is comparable with external radiation.
In patients with low-risk cancer, brachytherapy using iodine-125 or palladium-103 pellet implantation is recommended as monotherapy. It is a preferred option in these patients because it controls the cancer as effectively as surgery or EBRT, and patients experience much less urinary incontinence and erectile dysfunction.
Active surveillance Compared with observation and watchful waiting, active surveillance is a more structured program to track the progression of prostate cancer, allowing for earlier intervention if the patient's risk is found to increase on follow-up.
Active surveillance is recommended for low- and very low-risk patients.
Men following this have been found to have favorable levels of anxiety and distress.
Active surveillance
Compared with observation and watchful waiting, active surveillance is a more structured program to track the progression of prostate cancer, allowing for earlier intervention if the patient's risk is found to increase on follow-up.
Active surveillance is recommended for low- and very low-risk patients.
Men following this have been found to have favorable levels of anxiety and distress.

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