No evidence treatment of localized prostate cancer associated with improved surv

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Mon, 27 Sep 2004 22:27:29 -0400

 

 

[sSRI-Research] Cancer: No evidence that treatment of

localized prostate cancer associated with improved survival

Measurement of prostate specific antigen as screening test for

prostate cancer. Trials of treatment are needed before trials of

screening.

 

Sandhu S; Morris R; Matveev V; Kaisary AV.

BMJ, 312(7032):709; 1996 Mar 16.

 

This article emphasizes that there is no evidence demonstrating that

treatment of localized prostate cancer is associated with improved

survival.

When a patient is diagnosed with early prostate cancer, three options

are presented: watchful waiting (with treatment only when disease

progresses), radiation therapy, and prostate gland removal. There is

no evidence indicating that prostate gland removal is associated with

improved outcome.

In fact, the procedure carries a risk of mortality and significant

morbidity including impotence and incontinence. In addition, treatment

with radiation therapy has not been proven to yield better survival

rates than placebo. The role of prostate cancer screening is

questioned in light of the lack of benefits associated with available

prostate cancer treatments and in view of its negative psychological

impact on men. The authors conclude that before a screening program

can be recommended, evidence of a treatment benefit must be provided.

 

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Prostate cancer in Saskatchewan Canada, before and during the PSA era.

Skarsgard D, Tonita J.

Cancer Causes Control 2000 Jan;11(1):79-88.

 

The results of this study show that prostate cancer-specific death

rates in Canada have not decreased since introduction of prostate

specific antigen (PSA) screening, and routine use of this test is

therefore not recommended.

 

The researchers evaluated all cases of prostate cancer that were

diagnosed in Saskatchewan from 1970 to 1997. While the incidence of

prostate cancer rose sharply in 1990 after introduction of the PSA

screening, prostate cancer-specific death rates did not change from

the early 1980s to the late 1990s, suggesting that screening detects a

large number of cancers that would have probably never become

malignant, without affecting cancer specific mortality rates.

 

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Prostate carcinoma incidence and patient mortality: the effects of

screening

and early detection.

Brawley OW.

Cancer, 80(9):1857-63 1997 Nov 1.

 

This article emphasizes that, in the U.S., prostate cancer screening

is widely utilized, although there is no evidence indicating that it

use is associated with improved survival. While mortality rates from

prostate cancer don't seem to have been affected by screening, this

practice has resulted in the detection of a greater number of early

cancers and in the unnecessary treatment of many men in whom the

cancer would have remained dormant.

 

Until new evidence will demonstrate a survival advantage associated

with screening, unnecessary treatment and treatment-related

complications remain the only established consequences of prostate

cancer screening programs.

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Screening for prostate cancer is neither appropriate nor cost-effective.

Albertsen PC.

Urol Clin North Am, 23(4):521-30 1996 Nov.

 

This article underlines that screening for prostate cancer is

ineffective and puts a significant burden on health care resources.

The results of three studies have indicated that the health benefits

that can be associated with prostate cancer screening can be measured

in terms of days of life gained, not of months or years. In addition,

for one man to benefit from screening several patients will undergo

unnecessary treatment and some will be harmed from it. Given this

premises, the appropriateness of screening for prostate

cancer is seriously questioned.

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Prostate cancer screening: more harm than good?

Lefevre ML.

Am Fam Physician 1998 Aug;58(2):432-8.

 

This article emphasizes that the current recommendation of the

American Cancer Society and other medical organizations that men over

50 years of age be screened for prostate cancer is not supported by

scientific evidence. It is believed that early screening results in

the detection and treatment of a certain number of early stage cancers

that would have had an indolent course if left untreated. Some men,

therefore, as a result of screening, will undergo unnecessary

radiation treatment and prostate gland removal, and will

suffer from complications such as impotence and incontinence, without

receiving any proven benefit from treatment.

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Changes in prostate cancer incidence and treatment in USA.

Lu-Yao GL, Greenberg ER.

Lancet 1994 Jan 29;343(8892):251-4.

 

The results of this study indicate that between 1983 and 1989, the

incidence of prostate cancer in the U.S. rose by 6.4% per year. This

increase is attributed to the detection of a greater number of early

cancers through screening, while the incidence of advanced prostate

cancers has remained stable. Concurrently, during the same time

period, the number of prostatectomies (prostate gland removals) more

than trebled, particularly among older patients (aged 70-79). However,

the increase in number of patients undergoing prostate surgery did not

translate in an improved survival, since mortality rates remained

unchanged throughout the study period. These data indicate that

increasing screening efforts and increased surgical interventions were

not associated with improved survival in patients with prostate

cancer. Strikingly, surgeries were performed most often on older

patients, who are the least likely to benefit from it.

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Psychological reactions in men screened for prostate cancer.

Gustafsson O, Theorell T, Norming U, Perski A, Ohstrom M, Nyman CR.

Br J Urol 1995 May;75(5):631-6.

 

The results of this study show that prostate cancer screening is

associated with considerable psychological distress, especially in

patients who undergo prostate biopsy. The study evaluated levels of

serum cortisol (an hormone released in response to stress),

psychological reactions, and sleep patterns in a sample population of

2,400 men invited for prostate cancer screening.

 

The investigators found significantly higher levels of cortisol in the

blood of individuals during screening, compared to the levels found in

a correspondent sample of men during normal daily activities. The

highest levels were found in men who, after prostate screening, were

scheduled for biopsy. The results of a questionnaire also revealed

that screening was associated with significant psychological distress

and sleep disturbances.

 

The authors conclude that is important to direct screening to

high-risk individuals in order to reduce the risk of adverse

psychological reactions; furthermore they highlight the need for a

test with high specificity in order to reduce the incidence of false

positive tests leading to unnecessary diagnostic work-up and

interventions.

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Screening digital rectal examination and prostate cancer mortality: a

case-control study.

Richert-Boe KE; Humphrey LL; Glass AG; Weiss NS.

J Med Screen, 5(2):99-103 1998.

 

The results of this study indicate that prostate cancer screening

through digital rectal examination is not associated with a reduction

in prostate cancer mortality.

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Cancer Prevention in Primary Care: Screening for ovarian, prostatic,

and testicular cancers.

J Austoker.

BMJ 1994;309:315-320 (30 July).

 

This article highlights that none of the tests used for screening of

prostate cancer (rectal examination, prostate specific antigen, and

ultrasounds), have lead to a decrease in mortality. Prostate cancer

screening results in the detection of an increased number of early

stage cancers, most of which would have remained silent and never

progressed into aggressive cancer. Furthermore, the test leads to a

significantly high number of false positive cancer diagnoses. Some of

the cancers that are detected can be successfully removed, but for one

patient whose cancer has been detected before it has spread outside

the capsule, a large number of patients had undergone unnecessary

treatment.

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PROSTATE CANCER

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Causes of death in elderly prostate cancer patients and in a

comparison nonprostate cancer cohort.

Newschaffer CJ, Otani K, McDonald MK, Penberthy LT.

J Natl Cancer Inst 2000 Apr 19;92(8):613-21.

 

The results of this study show that men with prostate cancer who

receive aggressive treatment are significantly less likely to have

reported on their death certificate prostate cancer as a cause of

death, compared to men with prostate cancer who receive no treatment.

 

The study was conducted to determine the reliability and validity of

the information reported on the death certificates of men with

prostate cancer. For this purpose, the authors compared rates of death

in patients with prostate cancer with that of patients from the

general population without this disease. Forty percent

of patients with prostate cancer died from the disease.

 

While at a first look both groups had similar rates of death from

diseases other than prostate cancer, when the researchers evaluated

independently death rates of patients who received cancer treatment

from those of patients who did not receive treatment, they found that

patients who received treatment had a 51% greater chance to have

reported other cancers as a cause of death in their death certificate,

compared to the control group without prostate cancer. On the other

hand, patients who did not receive treatment had a 34% lower chance to

have reported other cancers as cause of death on their death

certificate, compared to the control group.

 

These data indicate that physicians introduce a bias when reporting

the cause of death in individuals with prostate cancer. In particular,

physicians of patients who have received prostate cancer treatment are

more likely to report other causes of death on their patients' death

certificates, while, on the contrary, physicians of patient with

prostate cancer who did not undergo treatment are significantly more

likely to report prostate cancer as a cause of death on their death

certificate, compared to other causes of death. These findings have

important implications since several epidemiological studies use death

certificates as a source of information. If the benefits of a

treatment for prostate cancer, for example, are evaluated on the basis

of death certificates data, than it may be wrongly concluded that

treatment is associated with a reduction in death from prostate cancer.

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Radical prostatectomy versus expectant primary treatment in stages I

and II prostatic cancer. A fifteen-year follow-up.

Graversen PH, Nielsen KT, Gasser TC, Corle DK, Madsen PO.

Urology 1990 Dec;36(6):493-8.

 

The results of this study show that prostate gland removal (radical

prostatectomy) does not improve survival in patients with localized

prostate cancer. One hundred eleven patients with stage I-II prostate

cancer were randomly assigned to undergo either surgical removal of

the prostate gland or no treatment. Survival rates in both groups were

evaluated during a 15-year follow-up period. No differences in

survival were observed between the two groups, indicating that

prostatectomy is not effective in the management of early stage

prostate cancer.

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Recent results of management of palpable clinically localized prostate

cancer.

Adolfsson J, Steineck G, Whitmore WF Jr.

Cancer 1993 Jul 15;72(2):310-22.

 

This study reviewed all available literature published from 1980 on,

to determine rates of survival in patients with localized prostate

cancer managed with watchful waiting (with treatment delivered only

when disease progresses), prostatectomy (prostate gland removal), or

radiation therapy.

 

Ten year-survival rates were 93%, 83% and 62% for patients managed

with prostatectomy, watchful waiting and radiation therapy, respectively.

A

lthough these data seem to show a survival advantage associated with

surgical treatment, this advantage is likely due to bias contained in

the trials, where patients were assigned to different treatments

without being randomized. Since individuals selected for surgery are

normally fitter than those who receive radiotherapy or no treatment,

they an inherent survival advantage which, if not taken in account,

may be wrongfully attributed to the procedure.

 

In view of these results the authors conclude that prostatectomy seem

to confer minimal benefits in terms of survival in patients with

prostate cancer, while radiation therapy may be associated

with harm.

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Localised prostate cancer: can we do better? There have been some

advances in local control, but little impact on survival. Editorial.

Prior, T. and Waxman, J.

BMJ 2000;320:69-70 ( 8 January ).

 

This article presents an overall review of the current evidence on the

impact of treatment on prostate cancer mortality. It is emphasized

that prostate cancer screening, although being associated with

increased rates of detection of early stage cancers, has not been

associated with increased survival. As for treatment, management with

radiation therapy has not resulted in improved survival, with patients

undergoing radiotherapy doing as good as those managed by simple

observation with initiation of treatment in case of disease

progression. Radical prostatectomy (prostate gland removal) has also

not been conclusively associated with improved survival, due to the

fact that the studies that found a survival advantage were not

randomized and were therefore subjected to the bias of selecting

physically fit individuals as surgical candidates. As for adjuvant

hormone therapy (anti-androgen therapy), its use was found to be

associated with better rates of local tumor control but not with

improved survival in a review of 20 randomized trials in which

patients were randomized to receive radiation therapy alone or

radiation therapy with anti-androgen therapy. Anti-hormonal

therapy is becoming an increasingly popular treatment option. But

since its use has not been translated in a clear survival advantage,

it is critical for physicians to weight the local benefits of this

form of treatment against its significant side effects: hot flushes,

loss of sexual function, and decreased sexual libido.

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The role of androgen deprivation in the definitive management of

clinically localized prostate cancer treated with radiation therapy.

 

Vicini FA, Kini VR, Spencer W, Diokno A, Martinez AA.

Int J Radiat Oncol Biol Phys 1999 Mar 1;43(4):707-13.

 

This study reviewed the available literature on the impact on survival

of a combination regimen consisting of anti-androgen treatment and

radiation therapy in patients with prostate cancer. Fourteen studies

were evaluated.

 

No study demonstrated improvement in prostate cancer survival. Four of

six studies in which patients were randomized to receive radiation

therapy only or radiation therapy plus hormone therapy, revealed no

survival benefit associated with anti-androgen treatment. Two studies

showed an improvement in overall survival. Combined data from all

studies indicated that hormone therapy improves local control without

a clear impact on survival. It is very important that physicians

weight the benefits of improved local control without survival

advantage against treatment side effects (hot flushes,

impotence and loss of sexual drive).

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Neoadjuvant total androgen suppression and radiotherapy in the

management of locally advanced prostate cancer.

Roach M 3rd.

Semin Urol Oncol 1996 May;14(2 Suppl 2):32-7.

 

This article highlights that a combination regimen consisting of

radiation therapy and anti-androgen treatment, although being

associated with increased local tumor control, does not improve

survival in patients with locally advanced prostate cancer.

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Quality of life in advanced prostate cancer: results of a randomized

therapeutic trial.

 

Moinpour CM; et al.

J Natl Cancer Inst, 90(20):1537-44 1998 Oct 21.

 

The results of this study show that treatment with flutamide, an

androgen receptor blocker, worsen the quality of life of patients with

advanced stage prostate cancer. The double-blind trial was conducted

on 739 patients with metastatic prostate cancer who, after undergoing

surgical castration, were randomized to receive flutamide or placebo.

Patients taking flutamide scored significantly worse at two of five

quality of life parameters assessed in the study. In particular,

treatment with flutamide was associated with significantly more

diarrhea and worse emotional functioning. In addition, patients

receiving flutamide benefited less from surgical removal of the

testicles than those receiving placebo.

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Does pelvic irradiation play a role in the management of prostate cancer?

 

Stock RG, Ferrari AC, Stone NN.

Oncology (Huntingt) 1998 Oct;12(10):1467-72.

 

This article highlights that whole-pelvis irradiation has not been

associated with improved survival, compared to prostate-only

irradiation, and its use is therefore not recommended in the

management of patients with prostate cancer.

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Adjuvant therapy for prostate cancer patients at high risk of

recurrence following radical prostatectomy.

 

Andriole GL.

Eur Urol, 32 Suppl 3():65-9 1997.

 

This article underlines that use of radiation therapy in patients with

prostate cancer that has spread outside the capsule is not associated

with improved survival. In addition, there is no evidence in support

of the widespread use of anti-androgen therapy.

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Maximal androgen blockade in combination with methotrexate for

treatment of metastatic prostate cancer.

 

Sagaster P; Flamm J; Micksche M; Fritz E; Donner G; Ludwig H.

J Cancer Res Clin Oncol, 122(3):171-76 1996.

 

The results of this study show that the addition of the anticancer

drug methotrexate to anti-androgen treatment with flutamide does not

result in improved tumor control or disease-free and overall survival

in patients with metastatic prostate cancer. Treatment with

methotrexate resulted in higher rates of adverse effects.

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