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Prostate cancer overview
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ELEVEN THINGS TO KNOW ABOUT PROSTATE CANCER
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A careful reading of materials on treatment of prostate cancer reveals that for those who need active intervention (versus wait-and-see) the rescission of the cancer produces the highest long-term survival.  It permits examination of the tissue, and better imaging results later.  Moreover, rather than having a dormant cancer, which can at a future date resume growth, those cells are removed.  See bottom of page for textbook explanation—jk.   

 

PROSTATE CANCER:

230,000 cases and 29,900 deaths in 04.  Median age at diagnosis 72.  Prostatic intraepithelial neoplasia (PIN) is precancerous histologic change.

 

Prostate cancer, left untreated, almost universally metastasizes to bone.

 

Once prostate cancer has left the gland, treatment makes little difference as to outcome--the same is true for the all but a few cancers.  It is widely acknowledged that surgery produces 50% of the cures, radation 40%m and chemotherapy 10%.  

 

An excellent technical site http://www.health.am/cr/prostate-cancer/#7   

 

STAGING (Merck)

T1        clinically inapparent by palpation or imaging.

 

T1c      Identified by needle biopsy

 

T2        Is palpable or reliably visible by imaging; confined to prostate

 

T2a      Involves of one love or less

 

T2b      >

 

T2c      both loves

 

T3        Extends through the prostate capsule

 

T3a      Unilaterally or bilaterally

 

T3b      Invades seminal vesicles

 

T4        Is fixed or invades adjacent structures other than seminal vesicles

 

 

Grading, based on the resemblance to tumor architecture to normal glandular structure, helps define the aggressiveness of the tumor.  Grading takes into account histologic heterogeneity  in the tumor.  2-4 well differentiated, 5-7 = moderate4ly differentiated, and 8-10 = undifferentiated. 

 

Undifferentiated prostate cancer, squamous cell, and transitional carcinomas respond poorly to the usual control measures.

 

http://www.health.am/cr/prostate-cancer/#7

CA Cancer J Clin 2002; 52:154-179
2002 American Cancer Society

 

The Current State of Hormonal Therapy for Prostate Cancer,

Beth Hellerstedt & Kenneth Pienta

 

http://caonline.amcancersoc.org

In general androgen deprivation induces a remission in 80 to 90 percent of men with advanced prostate cancer, and results in a median progression-free survival of 12 to 33 months.  At that time, an androgen-independent phenotype usually emerges, leading to a median overall survival of 23 to 37 months from the time of initiation of androgen deprivation.

 

The first VACURG study, published in 1967, randomized 1,764 Stage III and IV patients to one of four treatment options: placebo, orchiectomy plus placebo, DES 5 mg per day, or orchiectomy plus DES 5 mg per day.8 Orchiectomy was associated with a one-year survival rate of 73 percent and a five-year survival rate of 35 percent in Stage IV patients, compared with 66 percent and 20 percent in placebo-treated patients.  15% more survived 5 years and 7 % more 10 years. 

 

Diethylstilbestrol (DES), a semi-synthetic estrogen compound, was one of the first nonsurgical options for the treatment of prostate cancer. Widespread use has been limited, however, by the potential for significant cardiovascular and thromboembolic toxicity.  Initial studies from VACURG and the European Organization for Research and Treatment of Cancer (EORTC) used 3 to 5 mg of DES per day, and showed the remission rate of DES to be equivalent to orchiectomy.  DES at a dose of 3 mg per day has also shown equivalence to LHRH agonists in patients with locally advanced and metastatic disease in terms of overall survival and subjective improvement.  DES proved to be superior to flutamide alone in the treatment of metastatic disease.22 Several EORTC trials (30761 and 30762) demonstrated DES 3 mg per day to be equivalent to estramustine23 and cyproterone.24 The introduction of the LHRH analogs, with no significant cardiovascular toxicity, lack of breast enlargement, and significant reimbursement for clinicians, essentially ended the use of DES as a first-line hormonal therapy. DES is no longer mass produced for human use in the United States.

 

 

Meta study of 8,275 patients with metastic cancer had a survival rate of 25.4%, 23.6% for montherapy.  The five-year survival for all patients receiving CAB was 25.4 percent compared with 23.6 percent for patients receiving monotherapy.

 

The authors concluded that neoadjuvant androgen deprivation before radical prostatectomy was not indicated.

 

The retrospective review of the Mayo Clinic data included 707 men who underwent prostatectomy for Stage pT3bN0M0 disease, 147 of whom received adjuvant hormonal therapy (orchiectomy or oral hormones). Adjuvant therapy was associated with a significant improvement in biochemical progression-free survival (67 percent versus 23 percent at 10 years), systemic progression-free survival (90 percent versus 78 percent) and cause-specific survival (95 percent versus 87 percent). Which is to state a lower replace rate of 12%.

 

The Eastern Cooperative Oncology Group (ECOG) randomized 98 men with positive lymph nodes at the time of surgery to receive immediate antiandrogen therapy (with either goserelin or orchiectomy) or to be followed until disease progression.45 After 7.1 median years of follow-up, 7 of 47 men who received immediate antiandrogen treatment had died, as compared with 18 of 51 men in the observation group (p = 0.02). In the adjuvant group, three men died of prostate cancer, compared with 16 men in the observation group.  Very significant survival for those on antiandrogen therapy.

 

Interest has been increasing in the use of nonsteroidal antiandrogens as adjuvant therapy in patients with localized disease.46 Early results of a study of 365 patients with pT3N0 disease investigating the efficacy of flutamide (250 mg twice daily) given after radical prostatectomy demonstrated a 10% clinical recurrence rate at four years in the flutamide-treated patients compared with a rate of 31 percent for those receiving placebo (p = 0.002).

 

http://www.health.am/cr/prostate-cancer/#7

 

There are 3 zones, the peripheral zone accounts for 70% of the volume, central zone 25%, transition zone 5%.  Percentages of carcinoma are approximate the based on volume. About 40% of the deaths from prostate cancer occur in men over 80 years. 

 

Radiation therapy is preferred if complete surgical removal of the tumor is unlikely. A Gleason score of 7 or higher, a PSA level greater than 20, or evidence the tumor has penetrated the prostate capsule (stage T3) is an indication for primary radiation therapy.

 

 

 

HORMONE THERAPY IN CONJUNCTION WITH EXTERNAL BEAM RADIATION THERAPY

In 1997, the EORTC reported the results of 415 patients with locally advanced prostate cancer treated with external beam radiation versus external beam radiation plus goserelin for three years.50 At a median follow-up of 45 months, the Kaplan-Meier estimates of overall survival at five years were 79 percent for patients who received combined treatment versus 62 percent in the group treated with external beam radiation therapy alone (p = 0.001).  Eighty-five percent of surviving patients were free of disease at five years in the combined-treatment group and 48 percent in the group that received external beam treatment alone (p < 0.001). These data strongly suggested that adjuvant treatment in patients with locally advanced prostate cancer improved both local control and survival at five years. 85% DISEASE FREE VERSUS 38 WITH HORMONE THERAPY.  How ever other studies have revealed no improvement for those with 7-10 tumors, but 18%  advantage for those with 2 to 6 tumors. 

 

BRACHYTHERAPY  (radiation placed close to the surface of the body or within a body cavity.  Stone and colleagues biopsied a series of 296 patients, 115 of whom received complete androgen blockade for three months prior to implant and for three months after implant.57 Biopsies were positive in 4 of 115 (3.5 percent) who had received androgen deprivation versus 26 of 181 (14 percent) in those who had not (p = 0.002). When patients were separated into low risk (PSA < or = 10 ng/ml, Stage < or = T (2a), and Gleason score < or = 6) and high risk (all others), it was observed that low-risk patients did not benefit from the addition of hormonal therapy while the high-risk patients not treated with androgen deprivation had a significantly higher rate of positive biopsies (3.4 percent versus 21.1 percent; p = 0.003).   However, the next study failed to demonstrate an advantage for hormone therapy—conclusion was “remains unclear.”

 

 

 

Side Effects of Androgen Deprivation Therapy
Initially, hormonal therapy was considered to be well tolerated. Loss of libido was often the only adverse side effect mentioned to the patient. Several other toxicities have now been noted (Figure 4
). These include fatigue,65 weight gain,66 depression, osteopenia,67 anemia, muscle atrophy, gynecomastia,68 hot flashes,69 loss of cognitive function, and decrease in high-density lipoprotein.

 

Osteopenia/Osteoporosis
Once initiated, most men remain on hormonal therapy for years, if not the rest of their lives. Long-term treatment with androgen deprivation can lead to debilitating osteoporosis.
72,73 Even in a study of inter-mittent androgen blockade, evaluation of bone mineral density in the lumbar spine and hip revealed osteopenia in 46 percent and osteoporosis in 20 percent of patients.74 A similar study found that 50 percent of men on androgen blockade for at least 12 months had asymptomatic vertebral fractures.75 The precise incidence of clinically relevant fractures remains undefined.

 

the study was only of a 48-week duration, it underscored the startling amount of bone loss in patients on leuprolide alone for this period: 3.3 percent in the lumbar spine, 2.1 percent in the trochanter, and 1.8 percent in the total hip.

 

Cost also enters into decision-making when considering monotherapy versus CAB. A recent study evaluated the cost-effectiveness of different types of androgen ablation (DES, orchiectomy, medical monotherapy, and CAB), incorporating a quality-of-life analysis.97 Orchiectomy, LHRH agonists, antiandrogens, and CAB had similar effects on quality of life and survival estimates. The annual cost estimates included: DES: $36, LHRH agonist depot injection: $4,995, and antiandrogens: $2,842. Orchiectomy had a one-time cost of $3,360. CAB was associated with the smallest degree of benefit for the most relative cost. In this study, the lifetime cost of an antiandrogen plus orchiectomy was $20,700, while the cost of an antiandrogen plus LHRH agonist was $40,300. Figure 6 illustrates the relative lifetime costs of each therapy in comparison to effectiveness.

 

Data from multiple studies support a growing trend to treat patients earlier in their disease course, but currently, there is no single correct answer regarding timing of hormonal therapy for patients with PSA progression or asymptomatic metastatic disease.  

Cost and patient preference may assist in this choice. DES is available in the United States, but only from a few pharmacies. Because of cardiovascular toxicity, DES may be best reserved as a secondary hormonal option. Some patients may opt for alternative strategies, such as nutritional therapy or herbal supplements.

 

1989 August J Urology , 332-6

Node metastases & dying risk

1.  negative nodes 31% metastases & dying of prostate cancer17% at 10 years

single microscopic positive node risk of distant 80% & dying of 40%

multiple microscopic positive nodes, 84% & dying 66%

grosly or juxtaeregional nodes, 88% & dying 58%

 

Once prostate cancer is found within the pelvic lymph nodes the patient has systemic disease unlikely to be controlled by pelvic lymph node dissection and radiotherapy.

 

JAMA. Vol. 277 No. 6, Feb 12, 1997.

15 year study of men in Sweden average age 72 with prostate cancer.  642 patients all stages followed up until 1994.  Of the 541 deaths, prostate cancer accounted for 201 (37%).  Those with localized disease 11%; those with deferred treatment in this group had a similar survival rate to those who received initial treatment.  For those with locally advanced (T3-T4) the survival rate was

57%.  Those with distant metastases at the time of diagnosis the survival rate was 6%.  Conclusion for those with localized prostate cancer and without a reliable prognostic indicator, aggressive approach would result in substantial over treatment.

 

NATIONAL CANCER INSTITUTUE AT http://www.cancer.gov/cancertopics/treatment/prostate/hormone-therapy-use

Which urologist a patient with prostate cancer chooses may be more important in determining whether he receives hormone therapy than other factors such as his age or type of tumor, a new study reports.

"The urologist seems to play a role that is at least as important, if not more important, than tumor grade and patient characteristics," says lead researcher Dr. Vahakn B. Shahinian of the University of Texas Medical Branch in Galveston.

The findings suggest that a patient could go to two urologists and receive different opinions about whether to have the treatment, called androgen deprivation therapy because it blocks androgen hormones such as testosterone.

"This scenario is cause for concern because patients might be getting therapy that may not be in their best interest," says Dr. Shahinian.

Approximately half of all prostate cancer patients receive the therapy over the course of their disease. When given with radiation, the therapy can extend the survival of patients with locally advanced disease.

But there are not clear data for urologists to follow about when androgen deprivation therapy should be used for other patients. The treatment is expensive and potentially toxic, with side effects such as an increased risk of fractures and loss of sexual function.

During the 1990s, there was a dramatic increase in the use of androgen deprivation therapy for prostate cancer, even in cases where its benefit was unproven or highly improbable. This in part led to the new study.

The researchers linked the Surveillance, Epidemiology, and End Results (SEER) and Medicare databases to identify 1,800 urologists who treated 61,000 men diagnosed with prostate cancer at age 65 years or older. The most recent data were from 1999.

The urologist was responsible for about 20 percent of the variation in the use of hormone therapy, versus 10 percent for tumor grade and stage, and 4 percent for patient characteristics, according to findings in the June 21, 2006, issue of the Journal of the National Cancer Institute (JNCI). (See the journal abstract.)

Dr. Shahinian and his colleagues have begun to try to identify the characteristics of urologists that cause them to select the treatment.

A limitation of the study was the lack of information about prostate-specific antigen ( PSA) levels in participants. Rising PSA levels can be an indication for the therapy, so some patients might have received it based on evidence rather than physician judgment.

Nonetheless, the study shows that a powerful anticancer therapy is often selected based on a physician's intuition rather than on hard facts or evidence-based medicine, says Dr. Paul Schellhammer of Eastern Virginia Medical School, who wrote an editorial in JNCI.

Prostate cancer is an extraordinarily heterogeneous disease, and many cancers are diagnosed that will not affect the length or the quality of a man's life. "But hormone therapy represents a powerful remedy for patients who have progressive disease," Dr. Schellhammer adds.

The challenge for physicians, he suggests, is to offer androgen deprivation therapy to men with high-risk, potentially lethal prostate cancer early in their course of treatment and to withhold it from men with low-risk disease, thereby avoiding unnecessary risks.

Clinical trials are under way to clarify the picture of how and when the therapy should be used. Dr. Schellhammer predicts that a day will come when the treatment's use is guided by physicians but based on evidence rather than directed by physicians, as it is today.

 

 

Int J Radiat Oncol Bio Phys. 2005 Aug 1; 62(5): 1322-31

 

 Lack of benefit from short course of androgen deprivation for unfavorable prostate cancer patients treated with an accelerated hypofractionated regime.  1260 patients were treated with HDR prostate brachytherapy PSA ./= 10, Gleason score >/= 7 and .>/= T2b.  The androgen therapy did worse—possible because of delay in treatment with brachytherapy. 

 

 

 

 

The section below explains why the excision of the cancerous tissue is preferred when aggressive treatment is advisable. 

 

Campbell-Walsh, Urology, 9th ed., 2007

PROSTATE CANCER TREATMENT

 

The main advantage to radical prostatectomy is that if it is skillfully performed, it offers the possibility of cure with minimal collateral damage to surrounding tissue.  Further, it provides more accurate tumor staging by pathologic examination of the surgical specimen.  Also, treatment failure is more readily identified and the postoperative course is much more readily identified and postoperative course is much smoother than in the past.  Hospital stay is 1-3 days.  Moreover, radical prostatectomy significantly reduces local progression and distant metastases and improves cancer-specific and overall survival rates compared with watch and waiting.  Erectile dysfunction and rectal complications are less likely with nerve-sparing surgery than with radiotherapy.  Other common side effects include inguinal hernia and urethral stricture. 

 

Approximately half of patients develop erectile dysfunction after radiotherapy for prostate cancer.  This is caused by injury to the vasculature of the cavernous nerves and to the corpora cavernosa of the penis, usually beginning about 1 year after the completion of treatment.  (p. 2939) Comparisons of radical prostatectomy to radiation therapy are misleading because of different endpoints—surgery having the longer endpoint.   

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Disclaimer:  The information, facts, and opinions provided here is not a substitute for professional advice.  It only indicates what JK believes, does, or would do.  Always consult your primary care physician for medical advice, diagnosis, and treatment. 

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