autopsy studies-27% of men between 30 and 40 years of age and more than 60% of men in their eighties.
Small amounts of low-grade prostate cancer can be found in 30% of men over the age of 50.
Prostate cancer-in 2007 an estimated 218,890 new cases will be diagnosed and 27,000 are expected to die as a result of this disease.
Of the 27,000 men destined to die of prostate cancer in 2007 the great majority were diagnosed before the age of 75 years, therefore PSA screening unlikely the benefit most men who have a low probability of surviving 10 years.
The annual incidence of prostate cancer is about 176 cases per 100,000 men per year.
Most prevalent cancer among men in the U.S. with approximately 1.8 million men living with prostate cancer.
Mortality rate approximately 28 per 100,000 per year.
5-year survival for men diagnosed with local or regional disease was 61% in 1973, 74% in 1981 and 100% in 1995-2000 suggesting that the increased survival rates likely an artifact of PSA screening lead time bias.
The most common non-skin cancer in the U.S.
7th leading cause of death in the U.S.
Second most common cause of cancer related death in African-American men.
One in 6 men will be diagnosed with prostate cancer during their lifetime.
Lifetime rate of death from prostate cancer 3-4 percent.
Increase in the incidence over the last two decades related to use of prostatic specific antigen and the increasing rates are now reaching a plateau.
Second leading cause of cancer death in men.
Median age at diagnosis 68 years in white men and 65 years in African American men in 2002.
Older age, African American race and family history are the three nonmodifiable risk factors
Modifiable lifestyle factors include diet, smoking, exercise and weight may affect risk.
Obesity at time of diagnosis associated with increased risk of metastases and death.
Obesity associated with poor prognostic factors such as high grade and non localized disease.
Higher risk of biochemical recurrence of disease progression after radical prostatectomy.
Highest risk ethnic group is among African-Americans.
Mortality rate from prostate cancer among African Americans approximately twice that of white Americans.
Highest age standardized incidence in the U.S
Lower socioeconomic status associated with decreased survival rate in men with local or regional stage prostate cancer.
Median age at death due to prostate cancer is 78 years in white men and 76 years in African American men. Mortality rates have declined in the last 10 years from approximately 40,000 deaths per year in the early 1990s to estimated 29,900 in 2004.
Risk factors include age, family history, African American race and possible dietary fat intake. International incidence rates vary more than 65-fold from low-risk to high-risk populations.
Tomatoes and tomato based products, cruciferous vegetables, soy, legumes may be beneficial for prostate cancer.
Tomato source intake associated with a decreased risk of prostate cancer.
Vitamin E, selenium, omega 3-fatty acids, soy, polyphenols and isoflavones in the diet may be protective.
Milk and other dairy products, saturated fat, calcium high doses of zinc, grilled meats and heterocyclic amines may increased risk .
Daily use of aspirin and NSAIDs associated with reduced risk.
Substantially higher incidence in African American men compared to aged-matched white American men.
Migrant population studies show that men who move from low-incidence to higher-incidence countries experience a shift in risk toward that of men from the higher-risk areas, implying a role of environmental factors in the development of this disease.
Arises and develops mainly in the peripheral zone of the prostate.
The presence of prostate cancer in the fibroadipose tissue surrounding the prostate is referred to as extraprostatic extension.
50% of men with prostate cancer die of other causes, especially cardiovascular disease.
Expectant management is applicable for patients who are potentially curable.
Expectant management, known as active surveillance, considers the possibility that the malignancy is indolent, such that treatment can be deferred to possible avoided.
For patients managed with expectant care the PSA and digital rectal exam are required every three months for 2 years.
With expectant management the patient should be rebiopsied at three months or 1 year, or both.
With expectant management if the disease is stable for 2 years frequency of follow-up can be relaxed to 6 months-1 year.
With expectant management active treatment should begin if the PSA doubled in less than 3 years, an abnormal rectal exam manifested, or progression to a higher Gleason system score occurred.
Expectant management acceptable results have been obtained with observational periods up to 10 years (Klotz).
The risk of death within 15 years is estimated to be 4 to 30 percent, depending upon the age of the patient at diagnosis, the grade of the tumor.
Most men die with rather than from prostate cancer.
Men with low-grade disease rarely develop detectable metastases within 10 years of diagnosis.
Doubling times may exceed 4 years in patients with low-grade disesae
A minimum of 10-15 years of follow-up is desirable to provide a complete picture of prognosis.
Patients with nonmetastatic hormonally refractory prostate cancer have a median survival of 68 months, whereas patients with bone metastases have a median survival of only 40 months.
Androgen deprivation is the backbone of treatment for advanced prostate cancer but ultimately all patients develop disease progression even with castrate levels of testosterone.
Long term androgenic deprivation hormone therapy with locally advanced prostate cancer associated with decreased local failures and distant metastases, improved biochemical control and improved absolute survival compared to hormonal treatment given at the time of recurrent disease.
Estrogens effective treatment in prostate cancer but has more adverse cardiovascular risks than other approved hormonal treatments.
Tumor volume predictor of tumor recurrence.
With tumor volume less than 3.0 cm3 pelvic lymph nodes are cancer free.
More than 85% of patients with tumor volume less than 2cm3 remain free of disease.
In patients with tumor volume of 7 cm3 or greater tumor progression will occur in 85% of cases.
Patients with tumors with volume less than 0.5-1.0 cm3 rarely progress.
In peripheral and transition zone tumors smaller than 4 cm3 in volume the tumor remains confined to the zone but with larger tumor volumes bilateral prostate spread is more frequent.
Men with low testosterone levels have a much worse prognosis during subsequent chemical androgen ablation therapy.
The Gleason system is the standard grading system in the U.S.
D’Amico risk stratification categories patients as low (Gleason 6 or less, PSA 10 ng/mL or less and stage T2a or less), intermediate (Gleason 7, PSA 10-20 ng/mL and or stage T2b) and high risk (Gleason 8-10, PS greater than 20 ng/mL and or stage T2c or higher.
Prostate cancer-percent positive biopsies identified as an independent predictor of biochemical outcome.
Only 52% of patients with clinical organ-confined carcinomas are actually pathologically organ-confined at the time of radical prostatectomy.
96% of patients with extraprostatic extension have disease within 2.5 mm of the outer margin of the prostate capsule.
Newly diagnosed and untreated prostate cancer patients should undergo bone scan if there is bone pain, or elevated alkaline phosphatase.
From 70-80% of patients with metastatic prostate cancer have disease limited to bone.
The routine use of bone scan when the PSA is <20 ng/mL is to be discouraged.
Hormonal therapy results in tumor regression in the large majority of patients and reduces the PSA by over 95% in 90-99% of patients.
Use of second-line hormonal therapy is associated with lower response rates and no documented survival advantage.
Local recurrence incidence increases with pathologic Stage C disease, extracapsular extension and involvement of the seminal vesicles by tumor.
Involvement of the seminal vesicles is associated with a high-incidence of local tumor recurrence, distant metastases and decreased survival.
MRI and CT scans to evaluate lymph node metastases in the pelvis have low sensitivity of 0-30% for prostate cancer.
Adjuvant radiotherapy improves local control but does not increase survival in patients with pathologic stage T3/4.
In a trial of radiation plus permanent androgen deprivation therapy with T1-T4 disease there was a survival benefit of 53% for the combination treatment vs. 38% in patients treated with radiation alone at 10 years.
Randomized studies reveal an overall cancer specific survival advantage when androgen suppression therapy is added to external beam radiation compared to radiation alone in treating patients with unfavorable localized disease or with locally advanced prostate cancer.
Androgen deprivation therapy-RTOG 92-02 study of 1554 patients with locally advanced prostate cancer (T2c-T4N0-X and PSA less than 150 ng/mL treated with combined androgen blockade for 2 months before and 2 months after radiation therapy of 65-70 Gy, with subsequent randomization of monthly ADT for 2 additional years or no further treatment-resulted in an absolute 10% improvement in disease free survival, from 40 to 50%, in patients with extended ADT therapy, at 5 years.
10 year analysis of the RTOG 92-02 study revealed disease free survival higher for patients receiving 2 additional years of ADT 22.5% vs. 13.2%, while the overall survival was similar at 53.9% vs. 51.6%.
The addition of 6 months of androgen suppression therapy to external radiation therapy increases overall survival in localized but unfavorable risk prostate cancer (D'Amico).
More than 80% of prostate cancer patients develop erectile dysfunction as a result of surgery or external beam radiation therapy.
Approximately one-third of patients who undergo prostatectomy will have positive surgical margins.
Recent surgical series with selected patients with clinical stage T3 have survival rates of with 5 and 10 year prostate cancer specific survival rates around 85-99% and 72-92%, respectively.
Of patients treated with prostatectomy for T3a disease those that develop a PSA recurrence with have a PSA doubling time of ≥ 9 months in nearly 50% and ≥ 15 months in 33% of patients.
At 15 years after radical prostatectomy for selected patients with T3a disease only 16% of patients die from prostate cancer.
Serum PSA levels increase two decades before the clinical detection of cancer, indicating that early cancers begin when the PSA is below 0.5 ng per milliliter.
Only 15% of stage T1a untreated patients progress to clinical disease.
Stage III (T3N0M0) locally advanced disease 50%-60% have microscopic evidence of extraprostatic disease.
Metastasizes to supraclavicular lymph nodes in fewer than 1% of patients.
Measurements of PSA indicate persistent or recurrent tumor in up to 27-53% of patients treated for localized prostate cancer by curative potential of surgery or radiation therapy.
Approximately half of patients with clinical stage T3a disease after surgery will have not developed PSA recurrence at 15 years.
Patients with localized disease treated with radical prostatectomy 35% will have recurrent disease by 10 years.
With biochemical recurrence after radical prostatectomy 37% will develop clinical evidence of metastatic disease and 57% will die of prostate cancer within 5 years.
Biochemical recurrence defined as 3 consecutive increases in PSA level after external beam radiation.
Majority of patients with positive lymph nodes exhibit disease progression by 5 years.
99% of prostate cancers can be diagnosed at the localized and potentially curable stage by screening.
Disease specific 10-year survival following radical prostatectomy is about 85% and ranges from 94% for men with well differentiated cancer to 67% for men with poorly differentiated disease.
Bolla found the combination of hormonal therapy plus external beam radiation form locally advanced disease with a 5-year survival rate of 94% compared with 79% for men treated with radiation alone.
External beam radiation has a 10-year disease specific survival of 76% and ranges from 90% for well differentiated to 53% for poorly differentiated prostate cancer.
External beam radiation in low-risk patients with a PSA of 10 ng/ml or less, a Gleason score of 6 or less and a clinically staged T1c or T2a result in a less than a 2% a decade prostate-cancer specific mortality, whereas in patients with higher PSA levels or Gleason scores the estimated range is from 12-30%.
Prostate cancer-70 Gy external radiation is the standard dose at this time.
External beam radiation planning includes an approximate 5 mm safety zone around the prostate to account for subclinical extension of disease.
External beam radiation conventionally 70.2 Gy.
High dose conformed radiation rather than conventional dose external beam radiation for clinically localized prostate cancer results in fewer patients with increased PSA level 5 years after treatment and less likely to have locally persistent disease.
Randomized control study of patients with T1b through T2b localized prostate cancer with PSA levels less than 15 ng/mL to receive 70.2 Gy by external beam radiation vs. 79.2 Gy by conformal high dose radiation treatment resulted in 61.4% of men free of biochemical failure in the conventional group and 80.4% in the high dose group, i.e., a 49% reduction in the risk of failure at a median follow-up of 5.5years.
High dose conformal radiation 79.2 Gy.
Patients ideally suited for brachytherapy have a PSA<10, Gleason score <6 and stage T2a or lower.
Increasing radiation dose in localized prostate carcinoma undisputedly lowers the rate of biochemical recurrence and probably distal metastases as well.
Brachytherapy treatment only group 10-year disease free survival 66%, while patients treatment with the addition of external pelvic radiation achieve a disease free survival of 79%.
Involvement of seminal vesicle implies poor prognosis.
DES 1 mg per day improves 5-year survival of metastatic prostate cancer from 50% to 30% compared to placebo.
Orchidectomy with DES is better than orchidectomy alone and equal to DES alone in slowing prostate cancer progression.
The probability of a positive bone scan is less than 5% until total PSA is increased between 40 and 45 ng/mL.
After detection of an elevated PSA following a prostatectomy men develop clinically apparent metastases after a median of 8 years and die after a median of another 5 years.
Patients with Gleason score of <8 have a 73% chance of remaining free of disease at 5 years compared to a 40% probability for men with higher Gleason scores.
Tumor volume highly correlated with capsular penetration, positive surgical margins, seminal vesicle invasion and PSA.
With androgen ablation disease progression occurs in approximately 50% of patients within 12 the 18 months after the initiation of treatment.
DNA aneuploidy and a high proliferation index are related in prostate cancer.
High levels of RANKL (receptor activator of NF-κB ligand), its receptor (RANK), and protein osteoprotegerin (OPG) in prostatic cancer tissue than in normal prostate tissue.
Expression of RANKL, RANK and OPG correlates with Gleason score, tumor stage, tumor grade.
Serum PSA levels and androgen receptor status, suggesting they are involved with growth of prostate cancer and bone metastases.
Alterations in PTEN common with loss of protein expression occurring in >50% of advanced prostate tumors.
The use of three-dimensional conformal radiation techniques results in improved biochemical and clinical outcomes compared with conventional radiation treatment techniques for the treatment of clinically localized prostate cancer.
Patients with newly diagnosed prostate cancer do not require a bone scan if PSA < 20 ng/mL.
PSA declines of greater than 50% correlate with improved survival in patients treatment with second-line hormones or chemotherapy.
Median survival after becoming refractory to hormone therapy is generally less than 1 year.
Antiandrogen withdrawal response may be observed in up to 30% of patients, and a response to other secondary hormonal manipulations can be seen in up to 65% of patients.
Androgen deprivation as the primary treatment for advanced prostate cancer reduces the PSA by over 95% in 90-99% of patients.
Tumors from patients with metastatic prostate cancer have a higher degree of vascularization compared to prostate tumors from patients without clinical disease.
There is a higher microvessel density in prostate cancer than in adjacent hyperplastic or benign tissue.
Docetaxel therapy results in a greater than 50% decline of PSA in 38-46% of patients with metastatic prostate cancer refractory to hormones.
TAX 327 trial with 1006 patients with metastatic hormone refractory prostate cancer treated with prednisone 10 mg daily and randomized to docetaxel 75 mg/m2 every 21 days, docetaxel 30 mg/m2 weekly for 5 of every 6 weeks, or mitoxanthone 12 mg/m2 every 21 days for 30 weeks: resulted in median overall survival of 18.9 months in every three week docetaxel group vs 16.5 months in the mitoxanthone group.
TAX 327 trial analysis revealed that administration of every three week docetaxel with prednisone increased survival over the combination of mitoxanthone and prednisone.
Docetaxel survival benefit in hormonally refractive prostate cancer is 20-25% over mitoxanthone and prednisone therapy.
Mitoxanthone in combination with prednisone increases response rate and longer duration of response without increasing overall survival compared to patients treated with prednisone alone.
Docetaxel increases median survival benefit by 2-3 months compared to mitoxanthone.
Taxane based treatment results in a median time to PSA progression of 6-8 months.
In a randomized study of hormonally refractive patients with metastases treated with docetaxel plus estramustine or mitoxanthone plus prednisone revealed a marked improvement in survival time in the docetaxel and estramustine combination treatment, with a median survival time of 17.5 v. 15.6 months, a median time to progression of 6.3 vs. 3.2 months and PSA declines of at least 50% of 50% vs. 27% with no difference in objective tumor responses. Docetaxel/estramustine combinations result in a greater than 50% decline in PSA in 68% of chemotherapy naive prostate cancer patients refractory to hormones
Adding thalidomide to docetaxel may produce greater PSA reductions than docetaxel alone in patients with metastatic disease. Epidermal growth factor receptor (EGFR) signaling overexpressed more commonly in African American than in white patients.
Epidermal growth factor receptor (EGFR) signaling crucial for prostate cancer carcinogenesis and is critical to the development of androgen-independent disease.
Presence of HCGß in prostatic cancer cells associated with a poor prognosis.
Longer repeat polymorphisms in IGF1 and CYP19 genes are significantly associated with poorer survival in patients with metastatic disease.
There is a significant increase in risk of prostate cancer specific mortality in patients treated with radiation when core biopsy specimens reveal more than 50% tumor involvement compared to patients with less than 50% involvement on core biopsies.
There is presently no widely accepted method to quantify cancer volume in radical prostatectomy.
Endorectal MRI has a sensitivity of 95% and a specificity of 100% in detecting local recurrence at the site of anastomosis, near retained seminal vesicles and at lateral and anterior surgical margins, suggesting its role in defining local recurrence in patients with rising PSA levels after radical prostatectomy.
Identifying local recurrence after radiation with endorectal MRI is difficult due to prostatic shrinkage and diffuse T2 signal intensity making identification of viable tumor problematic.
A magnetic field strength of al least 1.5 Tesla (T) is required for quality studies of the prostate.
The use of an endorectal coil with a pelvic array coil improves quality of images and is recommended for prostate MRI study.
T2-weighted images provides adequate anatomical imaging of the prostate and is essential for detection, localization and staging of prostate cancer.
T-2 weighted images cancer of the prostate demonstrates decreased signal intensity within the high signal intense peripheral zone of the prostate.
In prostate cancer T-2 weighted images may have homogenous low signal intensity within the heterogeneous signal intensity transition zone.
MRI spectroscopy may be a reliable test to confirm relapse in prostate cancer after external beam radiation.
Most prostate cancer metastases begin within the marrow and MRI is more sensitive than bone scan or CT scan for identifying such abnormalities.
MR spectroscopic imaging (MRSI) demonstrates cancer based on assessment of concentrations of citrate, creatine, choline and polyamines.
Normal prostate contains high levels of citrate and with prostate cancer the level is reduced or undetectable and the choline level is elevated.
Polyamines are decreased in prostate cancer.
Increased choline+polyamines+creatine to citrate ratio identifies prostate cancer in the peripheral zone on MR spectroscopic imaging (MRSI).
Indium 111 capromab pendetide (ProstaScint) a radiolabeled murine monoclonal immunoglobulin G that recognizes the intracellular epitope of prostate specific membrane antigen utilized to identify with single photon emission tomography (SPECT) lymph nodes in patients with clinically localized disease, and in post prostatectomy patients with rising PSA.
A trial of selenium and vitamin E (SELECT study) taken alone or together in 35,000 men did not reduce the risk of prostate cancer.
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