Prostate cancer 61
Definition Prostate cancer is a malignant neoplasm that arises from the prostate gland and the most common form of cancer in men. localized prostate cancer is curable by surgery or radiation therapy but advanced prostate cancer is not yet curable.
Etiology The aetiology of PC is multi-factorial. Testosterone and DHT have an important role in the disease as males who undergo castration before puberty do not develop PC. Other factors which can influence the risk of developing PC include the following: Age Race Family history Diet Exposure to cadmium ( found in cigarette smoke), pesticides alkaline batteries, radionuclides and heavy metals.
Pathology The normal prostate is composed of acinar secretory cells that are altered when invaded by cancer. The major pathologic cell type is adenocarcinoma, more than 95% of cases. Prostate cancer can be graded. Welldifferentiated tumors grow slowly, whereas poorly differentiated tumors grow rapidly.
Metastatic spread can occur by local extension, lymphatic drainage, or hematogenous dissemination. Skeletal metastases from hematogenous spread are the most common sites of distant spread. The lung, liver, brain and adrenal glands are the most common sites of visceral involvement, but these organs are not usually involved initially.
Clinical presentation Localized disease / asymptomatic Locally invasive disease/ patients complain of alternation in urination manifested by urinary frequency, hesitancy, dribbling and impotency. Advanced disease/ back pain, spinal cord compression, lower extremity edema, pathologic fractures, anemia and weight loss.
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.
Digital rectal exam Digital rectal exam is commonly employed for screening of prostate cancer.
Prostate-specific antigen Prostate-specific antigen 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.
Imaging Trans rectal ultrasound (TRUS) of the prostate is commonly used to aid the diagnosis of PC. CT, MRI scan of the pelvis and isotope bone scan are also useful to stage PC, but they are not effective as screening method.
Diagnosis TRUS guided biopsy will help obtain samples from the peripheral and transitional zones of the prostate and other suspicious area.
Treatment GENERAL APPROACH TO TREATMENT The initial treatment for prostate cancer depends on the disease stage, Gleason score ( used to help evaluate the prognosis of men with prostate cancer ), 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 or radiation therapy is generally considered for localized prostate cancer. Complications of radical prostatectomy include blood loss, stricture formation, incontinence, fistula formation, anesthetic risk, and impotence. Nerve-sparing techniques facilitate return of sexual potency after prostatectomy.
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.
Recurrence risk Low: T1- T2a Gleason score 2-6 PSA< 10 ng/ ml Expected patient survival < 10 yr 10-20 yr Initial therapy - observation or Radiation - observation or Radiation or Radical prostatectomy ± pelvic lymph node dissection > 20 yr Radical prostatectomy ± pelvic lymph node dissection or Radiation
Recurrence risk Expected patient survival Initial therapy Intermediate: T2b- T2c Gleason score 7 or PSA 10 20 ng/ ml < 10 yr > 10 yr observation or Radiation or Radical prostatectomy ± pelvic lymph node dissection Radical prostatectomy ± pelvic lymph node dissection or Radiation
Recurrence risk Expected patient survival Initial therapy High : T3a- T3b Gleason score 8-10 or PSA > 20 ng/ ml < 5yr > 5 yr Observation or Androgen ablation Androgen ablation + radiation Or radiation (gleason < 7, PSA < 10ng/l ) Radical prostatectomy ± pelvic lymph node dissection( low volume)
Recurrence risk Very high: T3c-T4 Any T, N1-3 Any T, Any N, M1 Expected patient survival Initial therapy Androgen ablation or radiation+ Androgen ablation Androgen ablation or radiation + Androgen ablation or observation Androgen ablation
The major initial treatment modality for advanced prostate cancer is androgen ablation (e.g., orchiectomy ( testes removal) or luteinizing hormone-releasing hormone [LHRH] agonists with or without antiandrogens). After disease progression, secondary hormonal manipulations, cytotoxic chemotherapy, or supportive care is used for the patient who progresses after initial therapy.
Non pharmacologic therapy Bilateral orchiectomy rapidly reduces circulating androgen levels. Orchiectomy is the preferred initial treatment in patients with impending spinal cord compression or ureteral obstruction.
Pharmacologic therapy LH- RH agonists LH- RH agonists are a reversible method of androgen ablation and are as effective as orchiectomy in treating prostate cancer. LH-RH agonists available as Leuprolide, Leuprolide depot, Leuprolide implant, goserelin acetate implant. Leuprolide acetate is administrated once daily. Leuprolide and Goserelin acetate implant can be administered monthly, or every 12 or 16 weeks (Leuprolide depot, every 4 months).
Antiandrogens 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. In combination, with an LHRH agonist antiandrogens can reduce the LHRH agonistinduced flare.
Combined Hormonal Blockade The role of combined hormonal therapy, also referred to as maximal androgen deprivation or total androgen blockade. Some investigators consider combined androgen blockade to be the initial hormonal therapy of choice for newly diagnosed patients & for metastatic prostate cancer.
Drug treatment of second choice The selection of secondary or salvage therapies 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 testosterone levels are not suppressed (i.e., greater than 20 ng/dl) after initial LHRH agonist therapy, an antiandrogen or orchiectomy (surgical procedure to remove a testicle ) may be indicated. If testosterone levels are suppressed, the disease is considered androgen independent and should be treated with palliative salvage therapy. If initial therapy consisted of an LHRH agonist and antiandrogen, then androgen withdrawal should be attempted.
Androgen synthesis inhibitors can provide symptomatic relief such as aminoglutethimide and ketoconazol. After hormonal options are exhausted, palliative supportive therapy can be achieved with strontium-89 or samarium-153 lexidronam for bone-related pain, analgesic, corticosteroids, bisphosphonate, or local therapy.
Chemotherapy Docetaxel every 3 weeks, combined with prednisone, twice daily, has been shown to prolong survival in hormone-refractory metastatic prostate cancer. Androgen ablation is usually continued when chemotherapy is initiated. The combination with estramustine also improves survival in hormone-refractory metastatic prostate cancer. estramustine+ vinblastine Estramustine+ etoposide Estramustine + paclitaxel
Other combination exist such as Mitoxantrone + prednisone Ketoconazole + doxorubicin