Prostate Cancer

Epidemiology

Prostate cancer represents 32% of all cancers and cause 13% of all cancer deaths. In America Prostate cancer is the most common cancer (excluding skin cancer), and the 2nd leading cause of cancer death

In Romania the estimated incidence for 2000 was 28.08 to 100,000 inhabitants and mortality 12.93 per 100,000 inhabitants

Risk Factors

Age. The chance of prostate cancer increases rapidly after age 50. More than 60% of prostate cancers are diagnosed in men older than 65 years.

Race. African-american. Men have the highest incidence of prostate cancer documented in the world. In addition to the US prostate cancer death rate is 2 higher in African Americans compared with white men. Lifetime risk of cancer of poor black men is 9.8% and 8% in Caucasian men. The incidence of prostate cancer is 1.8 higher among men compared to white men blacks.

Family history. A father or brother with prostate cancer doubles a patient’s risk of prostate cancer. The risk is higher for men with several affected close relatives of prostate cancer, especially if their relatives were young when they were detected with cancer. An individual who has two first degree relatives with prostate cancer has increased 9 times higher lifetime risk of cancer prostate.

Diet A diet high in fat may play a role in prostate cancer. Studies have shown dietary risk factors for incidence and progression of various prostate cancer. African-American race, family history, low consumption of tomatoes, increased consumption of alpha-linolenic acid is associated with an increased incidence of prostate cancer. Weight, muscle mass index, low physical activity, smoking, low consumption of tomato juice, increased intake increased calcium and alpha-linolenic acid, African-American race and family history was associated with advanced stages of prostate cancer.

Histological Types

1. Acinar carcinoma 95% of all prostate tumors. It is derived from acinar cells of the prostate. Carcinomas tend to be multifocal and show a pattern heterogeneous glandular malignant growth. Adenocarcinoma of the prostate is the Gleason histological grade according to the system, giving points to 1-5 for two predominant histological types of prostate cancer. The two scores are added together to determine the Gleason score 2-10 noted.

Gleason score:

2-6 is a well differentiated adenocarcinoma, moderately differentiated adenocarcinoma July 1,

a poorly differentiated adenocarcinoma 8-10.

2. Mucinous adenocarcinoma 1% has frequently disseminates to the bone aggressive and is resistant to hormone therapy.

3. Endometrioid carcinoma. This variant is more aggressive than adenocarcinoma simple. It is associated with metastasis and has a poor prognosis.

4. Cell carcinoma signet ring has a poor prognosis

5. Comedocarcinoma reminds of poorly differentiated adenocarcinoma and has a poor prognosis

6. Adenochistic carcinoma

7. 0.5-1% squamous cell carcinoma is more aggressive than adenocarcinoma. Serum markers acid phosphatase and PSA (prostate specific antigen) is normal.

8. Primary transitional cell carcinoma of the prostate. Do not respond to hormone therapy, but respond to chemotherapy

9. Sarcomas 0.1% with two types rhabdomyosarcoma and leiomyosarcoma

10. Malignant Lymphoma

11. Metastases in prostate from other cancers are rare: acute lymphoblastic leukemia, the extension of the rectum or bladder cancer.

Signs and Symptoms: Most cancers early does not cause any symptoms, but some early signs are frequent urination, especially at night, blood in urine, difficulty starting urination or inability to urinate and urinary weak or painful. Subsequently signs of advanced disease: urinary frequency with nocturia, bladder tenesmus, weak urinary stream, terminal hematuria. Rarely inguinal lymphadenopathy with bilateral edema of the limbs, bone pain due to metastasis.

Paraneoplastic syndromes:

1. Systemic Fibrinolysis

2. Neuromuscular abnormalities

   Screening

At the moment there are insufficient data to recommend routine screening or prostate cancer. The American Cancer Society (ACS) does not recommend routine prostate cancer screening. ACS recommends for men at average risk, beginning with age 50 to be informed of the possibility of screening, early detection discussing the limits and benefits of prostate cancer.

Men at high risk include African-Americans that men with first-degree relative diagnosed with prostate cancer before age 65, should have a discussion on the appropriateness of screening starting age of 45 years. Men with high risk (have two or more close relatives diagnosed with prostate cancer at early ages) must have this discussion on the appropriateness of screening beginning with age 40 years. If a man chooses to be to be tested, the test is recommended PSA (prostate specific antigen) with or without rectal examination.

Prostate Biopsy

a) ultrasound guided needle biopsy is indicated in patients with PSA level> 4 ηg / ml and / or abnormal digital rectal. The best is the transrectal guided ultrasonography. Classic biopsies were made in June, three on each side of the gland at the top, middle and base. Recently insist that more targeted biopsies lateral peripheral zone of the gland cancer detection rate increases to 14-20%. If the biopsy is negative because it is not ruled out the presence of cancer in 13% -31% of patients with negative initial biopsy, subsequent biopsy will detect cancer. Therefore these patients will be evaluated further 6-12 months with PSA and rectal examination.

Diagnosis is established at 24% of annual cases when the indication is PSA levels> 4 ηg / ml and 45% of cases when the indication is PSA> 10 ηg / ml, abnormal rectal examination and ultrasonography hypoechogenyc injury.

b). Biopsy by TURP (transurethral prostate resection) for prostate adenoma detected in 5-10% of prostate cancer.

TNM classification

Primary Tumor (T)

Tx- tumor cannot be evaluated

T0- no signs of tumor

Tis – carcinoma in situ (PIN – prostatic intraepithelial neoplasia)

Injury impalpable

T1a- tumor found incidentally, involve less than 5% of pathological specimen

T1b – tumor found incidentally represent more than 5% of pathological specimen.

T1c – tumor detected by biopsy (after screening with PSA increased)

Palpable lesions limited to the organ

T2a – transrectal ultrasonography palpable or detected in one lobe <1.5 cm

T2b – transrectal ultrasonography palpable or detected in both lobes> 1.5 cm

Palpable lesions that surpassed body

T3a – Extracapsular extension

T3b – seminal vesicle invasion

T4 – invasion bladder, the external sphincter, levator muscles, pelvic wall invasion

Lymph nodes (N)

Nx – lymph nodes cannot be assessed

N0 – lymph nodes are invaded

N1 – pelvic lymph node metastases <5 cm

N2 – voluminous pelvic lymphadenopathy> 5 cm

N3 – para-aortic lymphadenopathy

Metastasis (M)

Mx – distant metastasis cannot be assessed

M0 – no distant metastases

M1a – non regional lymph node invasion

M1B – bone invasion

M1c – other metastatic locations

Adenocarcinoma of the prostate is the Gleason histological grade according to the system (due to marked morphological heterogeneity of prostate cancer), giving points to 1-5 for two predominant histological types of prostate cancer. The two scores are added together to determine the Gleason score of 2 to 10. Note If there is a single focal Gleason pattern 3, then reported Gleason score 3 + 3 will be = 6.

Gleason x – Gleason score cannot be assessed

Gleason ≤ 6-well differentiated (slight anaplasia)

Gleason 7 – moderately differentiated (moderate anaplasia)

Gleason 9-10- poorly differentiated / undifferentiated (marked anaplasia)

The diagnosis is confirmed by histopathological examination.

For primary tumor diagnosis and staging rectal examination is recommended, transurectala ultrasound, CT and M.R.I. Pelvic.

Lymph node dissection is necessary? For staging? Or for healing? Pelvic lymphadenectomy performed and the current standard is warranted in cases with PSA> 20 ng / ml, Gleason score greater than 6 and clinical stage T2, T3. A considerable controversy remains adequate treatment of patients with positive lymph nodes. Discussions remain on addressability initial treatment if hormone therapy or prostatectomy alone (with delaying hormone therapy until relapse is documented increases or PSA) is preferable, or whether androgen deprivation should start immediately after radical surgery. Currently any approach for the treatment of positive lymph nodes should be considered standard therapy.

For staging visceral metastatic disease are recommended: bone scan, bone scan, MRI, tumor markers (acid phosphatase, PSA). Bone scintigraphy is indicated in cases of poorly differentiated tumors, persistent bone pain, PSA values> 20 ηg / ml

Tumor markers

1. PSA (prostate specific antigen) is less than 4 normal ηg / ml.

Values ​​of PSA> 10 ηg / ml are suspicious of prostate cancer. The difficulty in interpretation occurs in PSA values ​​between 4 and 10 ηg / ml in benign conditions that may occur. PSA serum values ​​are not altered by digital rectal examination so PSA analysis can be performed before and after digital rectal examination.

Approximately 25% of patients with biopsy proven prostate cancer have normal PSA levels. The PSA values ​​between 4-10 ηg / ml if associated with prostate ultrasound and trans-urethral biopsy, prostate cancer is detected in 20% of patients, and the PSA levels of greater than 10 ηg / ml in 60% of patients.

PSA can be used to monitor therapeutic response. Increased PSA may precede relapse. After surgery a marked decrease in PSA levels confirm removing cancer. PSA levels correlate with tumor volume.

The PSA levels <10 ηg / ml in tumors limited to the prostate capsule.

The PSA value of 50 ηg / ml or more appears seminal vesicle invasion and pelvic lymphadenopathy. Values ​​of PSA> of 100ηg / ml is associated with disseminated disease.

2. The acid phosphatase is a glycoprotein which is increased in 60% and 80% of patients with disseminated disease (metastasis lymph nodes or visceral).

10% of patients with metastatic prostate cancer have normal levels of acid phosphatase. There are increases in acid phosphatase by digital rectal examination so that harvesting it is before DRE or 1-2 weeks after the operation.

TREATMENT

Therapeutic Indication

Std.T1a

1. Surveillance with clinical examination and determination of PSA frequency. Wait and watch (AU) is indicated as a primary option for patients with clinically localized tumors or moderately well differentiated, a life expectancy 15 years lower in patients with T1a tumors). PSA is repeated at 6 months, digital rectal repeat prostate biopsy at 12 months and repeated at 12 months.

2. young patients 40-60 years with high Gleason score (8-10), obtained by resection specimen weight less than 30g or more than 3 containing adenocarcinoma specimens indicate cure: radical prostatectomy or external beam radiotherapy

Std.T1b, T1c, T2a, PSA <10 ng / ml, Gleasson <6 (lower relapse risk)

Prostate cancer is found early. Treatment consists of either lymph node dissection radical retro-pubic prostatectomy plus pelvic lymph node invasion if probability is ≥2% or brachytherapy or external beam radiotherapy. The chances of healing are equally by both modalities. Patients with comorbidities in age with poorly differentiated tumors should be treated with radiotherapy.

25-30% of patients with pelvic lymph node metastasis were T1b state and local treatment outcomes are poor.

If you find lymph node metastases is recommended observation or androgen deprivation therapy.

In patients with seminal vesicle invasion, positive margins, extension Extracapsular or increased PSA after radical prostatectomy is recommended postoperative radiotherapy or observation. If you find lymph node metastases is recommended observation or androgen deprivation therapy.

Std. T2b, T2c, or Gleason> 7 or PSA10-20ng / ml (intermediate risk)

It is considered locally advanced prostate cancer.

a). Pelvic lymph node dissection Radical Prostatectomy plus node invasion if probability is ≥2%.

In patients with seminal vesicle invasion, positive margins, extracapsular extension or increased PSA after radical prostatectomy is recommended postoperative radiotherapy or observation. If you find lymph node metastases is recommended observation or androgen deprivation therapy. Or

b). Indicate external radiotherapy plus / minus neoadjuvant hormonal deprivation therapy / concomitant / adjuvant over a period of 4-6 months plus / minus brachytherapy and unlock endoscopic bladder neck.

Std T3a, or Gleasson 8-10 or PSA> 20 ng / ml (high risk of relapse)

a). Indicate external radiotherapy plus hormonal deprivation therapy neoadjuvant / concomitant / adjuvant over a period of 2-3 years and unlock endoscopic bladder neck.

b). Brachytherapy plus external beam radiotherapy is indicated plus brachytherapy plus / minus hormone deprivation therapy neoadjuvant / concomitant / adjuvant over a period of 4-6 months and unlock endoscopic bladder neck.

c). Pelvic lymph node dissection plus radical prostatectomy (selected patients without tumor fixed).

 In patients with seminal vesicle invasion, positive margins, extension Extracapsular or increased PSA after radical prostatectomy is recommended postoperative radiotherapy or observation. If you find lymph node metastases is recommended observation or androgen deprivation therapy.

Std T3b, T4 (very high risk of relapse)

a). Indicate external radiotherapy plus hormonal deprivation therapy neoadjuvant / concomitant / adjuvant over a period of 2-3 years and unlock endoscopic bladder neck. Or,

b). Brachytherapy plus external beam radiotherapy is indicated plus / minus hormone deprivation therapy neoadjuvant / concomitant / adjuvant over a period of 4-6 months and unlock endoscopic bladder neck. Or,

c). Pelvic lymph node dissection plus radical prostatectomy (selected patients without tumor fixed).

 In patients with seminal vesicle invasion, positive margins, extension Extracapsular or increased PSA after radical prostatectomy is recommended postoperative radiotherapy or observation. If you find lymph node metastases is recommended observation or androgen deprivation therapy. Or

d). Androgen Deprivation Therapy

Metastatic disease lymph node (N1)

a). Androgen Deprivation Therapy

or

b) . External radiotherapy is indicated, plus hormonal deprivation therapy neoadjuvant / concomitant / adjuvant over a period of 2-3 years and endoscopic unlocking of the bladder neck

Visceral metastatic disease (M1)

Combined androgen blockade is recommended (LHRH agonists combination with flutamide)

Therapeutic Methods

1. radical retro-pubic prostatectomy and staging lymphadenectomy is indicated in patients with localized tumors with life expectancy at least 10 years.

Contra prostatectomy are:

– Physiological age greater than 75 years

– Cancers with high Gleason score 9-10, higher PSA values

– Seminal vesicle invasion

– Pelvic lymph metastases

– Visceral metastases

Survival at 10 years for stage T1a, T1b, T1c, T2a is 92-97%.

2. Curative external radiotherapy

It is recommended:

– In patients with tumors T1, T2 and in combination with hormone ablation for tumors T3;

– In patients with contraindication for surgical treatment;

– Residual pelvic disease patients after surgery

Pelvic lymph node invasion patients

1. Endocrine therapy is the mainstay of treatment for advanced prostate cancer symptomatically.

Hormone therapy for first line:

a) In patients with bone invasion minimal (less than 5 lesions) and minimal symptoms it is recommended androgen deprivation therapy (ADT). Leuprolide is made by orchiectomy or 7.5 mg sc Goserelin 3.6 mg monthly or sc monthly.

b) In patients with disseminated bone disease or visceral metastases combined androgen blockade is recommended. After orchiectomy or medical castration, for 1 month add an antiangrogen (Flutamide or Casodex).

Hormone Therapy II line

Initial hormone ablation controls symptoms f or an average of two years, then the signs of metastatic disease reappear.

a) In patients who were treated with combined androgen blockade withdrawal of flutamide cause an improvement in symptoms in 10-25% of patients.