Prostate forms an important part of male reproductive system. Prostate is located just beneath the bladder encircling the urethra at its origin.
The main function of the prostate is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that, and along with spermatozoa, constitutes semen. The rest of the seminal fluid is produced by the two seminal vesicles. The alkalinity of seminal fluid helps neutralize the acidity of the vaginal tract, prolonging the lifespan of sperm.
Prostate is anatomically divided into 5 lobes – Anterior, Median, Posterior and two lateral lobes.
Histologically, it is divided into 3 lobes
Incidence of prostate cancer in US is 190/100,000 men. It forms about 33% of all non skin cancers in US. Highest incidence rates have been seen in Scandinavia and lowest in Asia. African Americans have higher incidence and mortality rate in US.
According to the Indian National Cancer registry report of 2001-2004 prostate cancer rank among the five most common cancers in Delhi, Mumbai and Bangalore registries. Incidence has increased primarily because of two reasons
1. Increased life expectancy: Median age of diagnosis is 68 yrs. Incidence increases sharply after 65 yrs. According to the autopsy data 70% of men older than 80 yrs of age and 40% men more than 50 yrs have pathological evidence of disease.
2. Increased prostate cancer screening owing to increased awareness.
All cancers if detected in early stage can be cured. In early stages of most cancers are asymptomatic. Most of the time when these cancers start producing symptoms, they have actually reached large sizes or have metastasized (i.e. spread to other body parts). Complete cure in these patients becomes very challenging. However if cancer is detected at early stage when the cell burden is less and disease is localized to organ of origin, cure rates can be very good. In addition smaller disease requires fewer treatment modalities to completely eradicate the cancer cells.
Prostate is one of the cancers where screening can help in detecting the disease at very early stages, giving us an option for complete cure.
Though there is some controversy regarding the necessity of prostate screening. The reason for the same is the fact that prostate cancer is very slow growing, and in patients in whom the life expectancy is less, either because of higher age or other co morbid conditions generally seen in older age group patients, symptoms may not actually appear. Another important thing to be considered is that screening tests should only be performed provided the patient is ready for further investigation if the screening test comes positive or suspicious.
Various organizations (the ACS, AUA, ACP, NCI, AAFP, ACPM, and the USPSTF) recommend that patients should discuss with health care professionals regarding the possible benefits, side effects, and assess for the need of screening tests considering their own situation.
* For general population with average risk of developing prostate cancer and life expectancy of atleast 10 years, screening should begin at the age of 50 years with Prostate-specific antigen (PSA) blood test and digital rectal exam (DRE) done on yearly basis.
* For men at high risk of developing prostate cancer (African American men and men who have a first-degree relative (father, brother, or son) diagnosed with prostate cancer at an early age (younger than age 65)), screening should begin at an age of 45 years.
* For men at even higher risk (those with several first-degree relatives who had prostate cancer at an early age), screening should begin at even early age (40 years).
Normal PSA levels depend on the age of the patient
40-49 years: < 2.5 ng/ml
50-59 years: < 3.5 ng/ml
60-69 years: < 4.5 ng/ml
70-79 years: < 6.5 ng/ml
In general values ranging from 0-4 ng/ml are considered normal, those between 4-10 ng/ml are considered suspicious, and that >10 ng/ml are mostly associated with prostate cancer.
Some non cancers pathologies like prostatitis and BPH can be associated with raised PSA, although the rise will always be less than that seen in prostate cancer. A course of antibiotics can lower serum PSA levels if the cause is prostatitis. Further diagnostic tests as discussed in work up need to be carried out to confirm the diagnosis.
Serum PSA levels along with digital rectal examination is the standard approach for screening. Other tests available act as an adjunct when doubt remains while interpreting of the results of screening tests, generally for PSA levels between 4-10 ng/ml. These include Prostate-Specific Antigen Density, Prostate-Specific Antigen Velocity and Free Prostate-Specific Antigen.
Prostate-Specific Antigen Density
A higher PSA density is associated with malignancy. For men with PSA between 4 to 10 ng/ml & a normal DRE; a prostate specific antigen density of > 0.15 has been suggested as discriminatory for presence of carcinoma.
Prostate-Specific Antigen Velocity
Basis of this test is that men with cancer should have more rapid rises in PSA levels than men without cancer. Serial PSA measurements are done to calculate the rate of rise in PSA, or PSA velocity. A rate of rise of >0.75 ng/mL per year has been associated with a higher frequency of cancer.
Free Prostate-Specific Antigen
PSA exists in body in two forms –free and complexed form. Ratio of the two will define the nature of the disease. The percent-free PSA in serum is higher in men with BPH than in men with a normal prostate or cancer and can be used to discriminate cancer from BPH.
The complexed-to-total ratio was higher and free PSA lower in patients with prostate cancer relative to those with benign prostatic hyperplasia.
A ratio of free to total PSA of ≤0.2 was most likely associated with prostate cancer. A ratio of ≤0.15 was associated with a higher Gleason score and poorer prognosis.
1. Endometrial biopsy
2. Endometrial Curettage
3. Ultrasonography (TAS and TVS)
4. Contrast Enhanced Computed Tomography
5. Magnetic Resonance Imaging
* Patients with localized prostatic carcinoma are frequently asymptomatic; the diagnosis is often made with a screening PSA test.
* Patients with locally advanced tumors have presented with bladder outlet obstructive symptoms such as urinary hesitancy, decreased force of the urinary stream, and post void dribbling s the tumor impinges on the membranous urethra.
* Chronic obstruction and bladder distention can lead to decreased compliance of the detrusor muscle that is manifested by symptoms of urinary frequency, urgency, and nocturia (increased urination at night).
* With local invasion into the urethra or ejaculatory ducts, patients may experiencehematuria (blood in urine) or hematospermia (blood in semen).
* As the disease penetrates the capsule of the prostate, there may be invasion into the neurovascular bundles that course along the lateral aspects of the prostate, leading to erectile dysfunction.
* Disseminated disease frequently manifests as Bone pain from distant osseous metastases.
Clinical history and clinical examination
Digital rectal examination
* Laboratory Complete blood cell count, blood chemistry profile
Serum PSA (total, free, percentage free)
Plasma acid phosphatases (prostatic/total)
* Radiographic imaging Magnetic resonance imaging ( MRI )with endorectal coil
Radioisotope bone scan (PSA >20)
Computed tomography ( CT )of pelvis
Chest radiograph (Chest X-Ray )(in patients with high risk for metastatic disease)
Transrectal ultrasonography (for biopsy guidance)
* Needle biopsy of prostate (transrectal, transperineal): A 6 quadrant and nowadays preferably a 8 quadrant biopsy is advisable
* Staging lymph node dissection (high risk for lymph node metastases)
Transrectal Ultrasonography: TRUS is used routinely for guidance during the transrectal biopsy and during prostate brachytherapy. However, only prostate cancers located in the peripheral zone can be reliably detected by ultrasonography.
Computed Tomography (CT Scan): The primary role of CT in prostate cancer is to determine the size of the gland, radiation therapy treatment planning, and assessment of pelvic nodal metastases. It is however difficult to detect any capsular extension, or seminal vesicle involvement.
Magnetic resonance imaging (MRI): Soft tissues are clearly identified using MRI. Currently, the best imaging study for prostate cancer is endorectal MRI. Both T1- and T2-weighted images are taken. T1 images can detect blood in the prostate, whereas T2 images help define the internal architecture of the prostate and seminal vesicles including any suspicious lesion. Any extracapsular extension (ECE) and seminal vesicle invasion (SVI), or invasion of the neurovascular bundles (NVBs) can be better picked up using MR Spectroscopy used along with MRI
Bone Scan: A bone scan detects for any distant site of bony involvement. Chances of having a positive bone scan are seen in patients with high PSA (>20 ng/ml).
All patients are staged depending on the disease extent. AJCC classifies patients into 4 stages
Stage I :Tumor limited to prostate gland detected histologically in <5% of the resected specimen, and the disease is low grade.
Stage II :Tumor limited to prostate gland detected histologically in <5% of the resected specimen, and the disease is intermediate or high grade.
Any tumor limited to the prostate of any grade.
Stage III : Tumor extending beyond the prostate capsule toextracapsular tissue or seminal vesicle of any grade
Stage IV : Tumor extending to other pelvic structures beyond the seminal vesicles, or involving lymph nodes , or extending outside the pelvic cavity
Staging of Endometrial Carcinoma
Prostate-Specific Antigen:In general, higher values are associated with larger tumor volumes and a more advanced stage, although there may be a wide range of values within any clinical T category
Gleason Grade:This entity is mentioned on the pathology report done for either biopsy or post operatively. Higher Gleason score is strongly associated with larger tumor volume, extension outside the prostate, probability of metastases, and duration of response to therapy.
Stage:Stage of the disease predicts outcome. Higher the stage poorer is the prognosis and less are the chances of complete cure
It is based on risk categorization
Low Risk: T1-T2 and Gleason Score 2-6 and PSA <10ng/ml
Intermediate risk : T2b-T2c or GS 7 or PSA 10-20ng/ml
High Risk: T3a or GS 8-10, or PSA >20ng/ml
Very High risk: T3b- T4
T1-T2a and Gleason Score 2-6 and PSA <10ng/ml
|For life expectancy < 10 yrs
RT (3D CRT/IMRT with IGRT or Brachytherapy)
|For life expectancy >= 10 yrs
RT (3D CRT/IMRT with IGRT or Brachytherapy)
T2b, Gleason Score 7, PSA 10-20
|For life expectancy < 10 yrs
RT + Short term hormonal treatment (4-6 months)
|For life expectancy >= 10 yrs
||RT + Short term hormonal treatment (4-6 months) ( preferred),
Surgery + adjuvant RT +/- short term HT (preferred)
|High Risk: T3a, GS 8-10, or PSA >20
||Long term hormonal treatment (2-3 yrs) + RT (3D CRT or IMRT with IGRT)
RT + Short term hormonal treatment (4-6 months) in selected patients with a single adverse high risk factor
|Locally advanced Very High risk: T3b- T4
||Definitive RT + Short term hormonal treatment (4-6 months)
Long term hormonal treatment (2-3yrs) alone
||Androgen ablation +/- palliative RT +/- bisphosphonates.
For Hormone refractory disease, Chemotherapy docetaxel + predinosolone or estramustine
|Residual disease or recurrence after surgery
||If persistent local disease or high risk of local residual disease à RT +/- HT.
If no evidence of persistent local disease or high risk of metastases à HT or observation +/- RT
|Residual disease or recurrence after RT
||If Bx +ve & no evidence (or low risk) of metastases, surgery or salvage brachytherapy.
If metastatic and not a candidate for local therapy, androgen ablation or observation