ONCOLOGY

UNIT
PROSTATE CANCER
 INTRODUCTION

• Prostate cancer is a malignant neoplasm that arises from the

prostate gland.
• Prostate cancer has an indolent course; localized prostate
cancer is curable by surgery or radiation therapy but
advanced prostate cancer is not yet curable.

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 PATHOPHYSIOLOGY

• In prostate cancer, the cells of these prostate glands mutate

into cancer cells. Mutation is majorly in p53 gene, BCL2 and
ERK5 or alteration in Akt kinase signaling contribute toward
the development of prostate cancer.
• The prostate glands require hormones, known as androgens
that are involved in cell survival and apoptosis. Androgens
include testosterone, dehydroepiandrosterone and
dihydrotestosterone.

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 PATHOPHYSIOLOGY

• Initially, small clumps of cancer cells remain confined to prostate

glands, a condition known as carcinoma in situ or prostatic
intraepithelial neoplasia (PIN).
• Over time, these cancer cells begin to multiply and spread to the
surrounding prostate tissue forming a tumor. Eventually, the tumor
may grow large enough to invade nearby organs such as the nearby
lymph nodes or the rectum, or metastasize to bone, lymphatic system
and bladder.
• The lung, liver, brain, and adrenal glands are the most common sites of
visceral involvement.

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 CLINICAL PRESENTATION
• Localized prostate cancer is usually asymptomatic.
• Locally invasive prostate cancer is associated with ureteral dysfunction ,
such as alterations in micturition.
• Patients with advanced disease present with back pain and stiffness.
• Untreated spinal cord lesions can lead to cord compression. Lower
extremity edema can occur as a result of lymphatic obstruction.
Anemia and weight loss are nonspecific signs of advanced disease.

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 Risk Factors
• A complete understanding of the causes of prostate cancer remains
elusive.
Obesity
Age
Family History
Lower levels of Vit. D
Prostatitis
Elevated Blood levels of Testosterone

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 SCREENING

• Screening for prostate cancer is controversial. The American Cancer

Society recommends baseline prostate-specific antigen (PSA) and digital
rectal exam (DRE) beginning at age 50 years for men of normal risk.
• PSA is a glycoprotein produced and secreted by the epithelial cells of
the prostate gland. Acute urinary retention, acute prostatitis, and
benign prostatic hypertrophy (BPH) influence PSA, therefore limiting
the usefulness of PSA alone for early detection.
• PSA is a useful marker for monitoring response to therapy.

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 SCREENING

• Biopsy
• MRI and CT Scan: To access the extension into the bladder
and lymph nodes for staging the cancer and to evaluate bone
metastasis.

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 GENERAL APPROACH TO TREATMENT

• The initial treatment for prostate cancer depends on the disease stage,
Gleason score, presence of symptoms, and patient’s life expectancy.
• Expectant management, also known as observation or watchful
waiting, involves monitoring the course of the disease and initiating
treatment if disease progresses or the patient becomes symptomatic.
PSA and DRE are performed every 6 months.
• Radical prostatectomy and radiation therapy are generally considered
equivalent for localized prostate cancer, and neither has been shown to
be superior to observation alone.

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 • Men with disease confined to the prostate (T1 or T2a), no symptoms,
Gleason score of 2 to 6, or PSA of less than 10 ng/mL are at low risk for
recurrence and have a high 10-year survival rate.
• Men with disease involving more than Gleason score of 7, or PSA of 10
to 20 ng/mL are at intermediate risk for recurrence. If life expectancy
is less than 10 years, options are expectant management, radiation
therapy, or radical prostatectomy. If life expectancy is more than 10
years, options are prostatectomy or radiation therapy.

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 • Men with disease localized to the periprostatic area (T3), Gleason
score of 8 to 10, or PSA of more than 20 ng/mL are at high risk for
recurrence and should be treated with androgen ablation for 2 to 3
years combined with radiation therapy.
• Men with disease fixed or invading adjacent structures other than the
seminal vesicles (T4) are at very high risk for recurrence. Androgen
ablation should be initiated at diagnosis instead of waiting for the
onset of symptoms.
• The major initial treatment modality for advanced prostate cancer is
androgen ablation. After disease progression, secondary hormonal
manipulations, cytotoxic chemotherapy, and supportive care are
used.

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 SURGERY AND RADIATION THERAPY
• Prostatectomy and radiation therapy are potentially curative but are
associated with complications that must be weighed against expected
benefit. Consequently, many patients postpone therapy until the onset
of symptoms.
• Acute complications of radiation therapy include cystitis, proctitis,
hematuria, urinary retention, penoscrotal edema, and impotence.
Chronic complications of radiation therapy include proctitis, diarrhea,
cystitis, enteritis, impotence, urethral stricture, and incontinence.

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 HORMONAL THERAPY

• The goal is to reduce levels of hormones, called androgens, in

the body, or to prevent them from reaching prostate cancer
cells. There are different types of drugs that lower
testosterone levels.

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 Luteinizing Hormone-Releasing
Hormone Agonists
• Drugs called luteinizing hormone-releasing hormone (LHRH) agonists,
which prevent the secretion of a hormone called luteinizing hormone.
• LHRH agonists provide response rates of approximately 80%, which is
similar to that of orchiectomy.

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• Examples of LH blockers include
Leuprorelin
Goserelin Acetate
Buserelin
Triptorelin
Histrelin
• LH blockers are given as injections or as implants under the skin.

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 Antiandrogens
• Anti-androgens stop androgens from working by binding to the
receptors and stop testosterone to bind with receptors so that cancer
can’t be able to grow.
• Monotherapy with flutamide, bicalutamide, and nilutamide is no
longer recommended due to decreased survival as compared with
patients treated with LHRH agonist therapy or orchiectomy.
Antiandrogens are indicated for advanced prostate cancer only when
combined with an LHRH agonist.

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 Antiandrogens
• Examples of anti androgens include
Bicalutamide
Flutamide
Enzalutamide
• Anti-androgen treatment may be combined with LH blocker as
first-line hormone therapy. This is called combined androgen
blockade (CAB).

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 DRUG DOSE ADVERSE EFFECTS
Leuprolide(depot) 7.5mg IM monthly or 22.5 mg Increased bone pain, hot
IM/3 months flashes, erectile impotence, and
injection-site reactions.

Goserlin (implant) 3.6mg SC monthly or 10.8 mg SC Hot flashes, decreased libidp

q 3 months and GI disturbances

Triptorelin depot 3.75 mg IM monthly Increased bone pain, hot

• flashes, erectile impotence, and
injection-site reactions

Flutamide 750mg/day Methemoglobinemia,

gynecomastia, hot flushes, LFT
abnormalities, diarrhea

Bicalutamide 50 mg/day gynecomastia, hot flushes, liver

function test abnormalities,
diarrhea

Nilutamide 300mg/day for first month causes visual disturbances,

then150mg/day alcohol intolerance, constipation
and interstitial pneumonitis.

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 Combined Hormonal Blockade
• The role of combined hormonal therapy, also referred to as maximal
androgen deprivation or total androgen blockade, continues to be
evaluated.
• Randomized trial results are mixed when candidates for second-line
therapy are treated with combinations of antiandrogens plus either
LHRH agonists or orchiectomy.

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 Combined Hormonal Blockade
• Some investigators consider combined androgen blockade to be the
initial hormonal therapy of choice for newly diagnosed patients
because the major benefit is seen in patients with minimal disease.
Some argue that treatment should not be delayed because combined
androgen deprivation trials demonstrate a survival advantage for
young patients with good performance status and minimal disease who
were initially treated with hormonal therapy.
• Until definitive trials are published, it is appropriate to use either LHRH
agonist monotherapy or combined androgen blockade as initial therapy
for metastatic prostate cancer.

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 •

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 SALVAGE THERAPY
• The selection of salvage therapy depends on what was used as initial
therapy. Radiotherapy can be used after radical prostatectomy.
Androgen ablation can be used after radiation therapy or radical
prostatectomy.
• If initial therapy consisted of an LHRH agonist and antiandrogen, then
androgen withdrawal should be attempted. Mutations of the androgen
receptor may allow antiandrogens to become agonists. Withdrawal
produces responses lasting 3 to 14 months in up to 35% of patients.

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 SALVAGE THERAPY
• Bisphosphonates such as pamidronate and zoledronic acid may prevent
skeletal morbidity, such as pathologic fractures and spinal code
compression, when used for hormone-refractory prostate cancer in
patients with clinically significant bone loss. Usual dosages are
pamidronate, 90 mg every month, and zoledronic acid, 4 mg every 3 to
4 weeks.
• After hormonal options are exhausted, palliation can be achieved with
strontium-89 or samarium-153 lexidronam for bone-related pain,
analgesics, glucocorticoids, local radiotherapy, or chemotherapy.

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 CHEMOTHERAPY
• Docetaxel, 75 mg/m2 every 3 weeks, combined with prednisone, 5 mg
twice daily, has been shown to prolong survival in hormone-refractory
metastatic prostate cancer. The most common adverse events were
nausea, alopecia, and myelosuppression. Docetaxel can also cause fluid
retention and peripheral neuropathy.
• The combination of estramustine 280 mg by mouth three times daily on
days 1 to 5 and docetaxel 60 mg/m2 on day 2 of a 21-day cycle also
improves survival in hormone-refractory metastatic prostate cancer.
Estramustine causes a decrease in testosterone and a corresponding
increase in estrogen, which results in an increase in thromboembolic
events, gynecomastia, and decreased libido.

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 EVALUATION OF THERAPEUTIC OUTCOMES

• For definitive, curative therapy, objective parameters to monitor

include primary tumor size, involved lymph nodes, and tumor markers
such as PSA. PSA level is checked every 6 months for the first 5 years,
and then annually.
• With metastatic disease, clinical benefit can be documented by
evaluating performance status, weight, quality of life, analgesic
requirements, and PSA or DRE at 3-month intervals.
• Patients should be monitored for treatment-related adverse events,
especially events that are amenable to intervention.

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 Refrences
• Wolf AM, Wender RC, Etzioni RB, Thompson IM, et al. American Cancer Society guideline for
the early detection of prostate cancer: update 2010. CA Cancer J Clin. 2010 Mar-Apr.
60(2):70-98
• [Guideline] U.S. Preventive Services Task Force. Screening for Prostate Cancer: US Preventive
Services Task Force Recommendation Statement. JAMA. May 8, 2018. 319(18):1901-1913.
• PDQ Adult Treatment Editorial Board. Prostate Cancer Treatment (PDQ®). National Cancer
Institute. Available at
http://www.cancer.gov/cancertopics/pdq/treatment/prostate/HealthProfessional/page4.
February 5, 2019; Accessed: August 6, 2019.

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