Screening Works: Prostate Cancer

 

Death Rate Drops to Lowest Mark Ever

Rate for African American men lowest in 29 years

Prostate cancer death rates dropped 32.5 percent in 10 years, according to new reports, possibly as a result of a dramatic increase in early detection. The mortality rate for African American men is the lowest since 1977, but it is still 2.36 times the rate for Caucasian men.

If the disease is caught early, nearly 100 percent of men are still alive five years after diagnosis, but if the cancer has already spread to a distant location, the five-year survival rate is only 34 percent. Since 1993, the percentage of men with distant prostate cancer at the time of diagnosis has dropped by 40 percent.

The PSA test, introduced in the mid 80’s, spurred an increase in prostate cancer diagnoses peaking at around 1992. The rapid increase in early detection and subsequent drop in the death rate since 1993 could be attributed to widespread use of the PSA test, adding to the growing body of evidence the PSA test saves lives.

“More lives are being saved every day, through advances in treatment and early detection,” said National Prostate Cancer Coalition CEO Richard N. Atkins, M.D. “It’s important to get active, and tell elected officials to spend more funds on prostate cancer research. Together, we can drop the mortality rate by another 32 percent in a few years.”

The NPCC using results from the SEER Database reported a reduction of 32.5% in the mortality rate. This reduction is directly related to early detection and treatment by the use of PSA testing. How will anti-screening forces explain such reduction while supporting the notion that PSA is not a useful marker?

Source: NPCC Website: http://www.fightprostatecancer.org/site/PageServer?pagename=homepage

LEARNING FROM HISTORY

THE NATURAL HISTORY OF UNTREATED PROSTATE CANCER

CURRENT EVIDENCE

A survivor’s view

Ralph Valle

Prostate cancer has a natural history. It was written long before the advent of the PSA era, and the

best documented details of that history exist in the Scandinavian countries cancer registries and

prostate cancer studies that depict what happens when prostate cancer goes untreated.

For the most part, between 1970 and 1990 prostate cancer in that part of Europe was treated

conservatively. This treatment consisted in the palliation of symptoms if they existed. Otherwise, if

a man was asymptomatic nothing was done. By looking at what happened with untreated prostate

cancer we could learn how the disease behaves undisturbed.

There is need to clarify that the existing data is a bit corrupt because as mentioned before, if a man

was symptomatic he might have been hormonally suppressed with an orchiectomy or treated with

estrogen to abate symptoms and STILL reported as on conservative treatment. As we know,

depending on the stage of the disease, hormone suppression can alter the natural progression of

prostate cancer and potentially increase survival. This complicates the situation when the data is

mixed, but it still gives an indication of how prostate cancer behaves in such setting; that is untreated

or treated with hormone suppression in a delayed form and no definitive localized treatment.

What then has happened when prostate cancer goes untreated? There are several studies with several

conclusions:

1. Johansson JE et al did a population-based study at Orebro, Sweden. A group of 642 patients with

prostate cancer of any stage, consecutively diagnosed between 1977 and 1984 at a mean age of 72

years with complete follow-up to 1994. RESULTS: In the entire cohort, prostate cancer accounted

for 201 (37%) of all 541 deaths. Among 300 patients with a diagnosis of localized disease (T0-T2),

33 (11%) died of prostate cancer. In this group, the corrected 15-year survival rate was similar in 223

patients with deferred treatment (81%; 95% CI, 72%-89%) and in 77 who received initial treatment

(81%; 95% CI, 67%-95%). The corrected 15-year survival was 57% (95% CI, 45%-68%) in 183

patients with locally advanced cancer (T3-T4) and 6% (95% CI, 0%-12%) in those 159 who had

distant metastases at the time of diagnosis. CONCLUSION: Patients with localized prostate cancer

have a favorable outlook following watchful waiting, and the number of deaths potentially avoidable

by radical initial treatment is limited. Without reliable prognostic indicators, an aggressive approach

to all patients with early disease would entail substantial overtreatment. In contrast, patients with

locally advanced or metastatic disease need trials of aggressive therapy to improve their poor

prognosis.

2. Gronberg H et al did a similar study, but the study population was composed of 6514 patients

diagnosed with prostate cancer during 1971 to 1987 in northern Sweden. For those who died during

follow-up, the cause of death was determined from the comprehensive Swedish registry data

(population registries and causes of death registry). RESULTS: About 85% of these patients died

during the 7 to 23 years of follow-up, and the prostate cancer-specific mortality was estimated to be

55%. Age at diagnosis was found to be a strong predictor of prostate cancer death. Patients

diagnosed before the age of 60 had an 80% risk of dying of prostate cancer, whereas those over 80

years of age at diagnosis had less than a 50% risk of prostate cancer-related death. CONCLUSIONS:

The prostate cancer mortality is high but decreases with older age at diagnosis. We found, using data

from the causes of death registry, that the relative survival and the cause-specific survival of these

patients were compatible with each other.

3. Gronberg H et al. Patient age per se can be a significant prognostic factor in prostate cancer. To

investigate this issue age-specific relative survival was analyzed, and the number of years lost due

to this disease was calculated in a large and unselected cohort of 6,890 prostate cancer patients

diagnosed between 1971 and 1987 in the northern region of Sweden. The tumor grade was derived

from filed notification forms, which showed 26.4% well (grade 1), 40.0% moderately (grade 2) and

17.7% poorly (grade 3) differentiated tumors. There was an overrepresentation of grade 3 tumors

among the youngest patients. The age-specific relative survival rate did not differ significantly

among different age groups and slight differences almost vanished when adjusting for tumor grade.

This finding does not support the view that tumors appearing in younger patients are more aggressive

per se. However, loss of life expectancy differed significantly among all age classes and in all 3

grades. In patients with grade 1 tumors the years lost due to prostate cancer ranged from 11.0 to 1.2

in the youngest and oldest age strata, even though the relative survival was approximately 0.70 in

all age classes. It was concluded that even if relative survival is constant with patient age, the

absolute impact of prostate cancer at different ages varied substantially as indicated by loss of life

expectancy. This finding might indicate that younger prostate cancer patients should be given more

aggressive treatment than older patients.

4. Adolfsson J et al., PURPOSE: We prospectively investigated long-term survival in select men

with locally advanced, nonmetastatic prostate cancer managed with deferred treatment.

MATERIALS AND METHODS: A total of 50 patients with prostate cancer clinically outside the

prostatic capsule and without distant metastases were included in a surveillance protocol. The men

were treated if and when symptoms occurred or upon request. The series was followed until

December 1994. No patient was lost to followup. RESULTS: Median patient age at diagnosis was

71 years. All patients were followed more than 144 months or died before then. Actual (cumulative

incidence) overall and disease specific survival rates at 5, 10 and 12 years were 68 and 90, 34 and

74, and 26 and 70%, respectively. A third of the patients had not received antitumor treatment at

followup or before death. CONCLUSIONS: When managed with deferred treatment non-poorly

differentiated, locally advanced nonmetastatic prostate cancer seems to have a poorer survival

outcome than similarly managed clinically localized prostate cancer. However, compared with other

treatments and in terms of survival deferred treatment may be an option for select patients with such

tumors and a life expectancy of 10 years or less.

5. Adolfsson J From 1978 to 1982, 172 patients with T1-3, Nx, M0 prostate cancer were included

in a surveillance protocol with deferred treatment on symptomatic progression. The median age at

diagnosis was 68 (38-89) years. The disease-specific survival at 10 years was 80% for the total

series, 84% for the subgroup with T1-2 tumors, and 92% for patients with T1-2 tumors diagnosed

when the patients were less than 70 years old . For the subgroup with T3 tumors, the disease-specific

survival at 9 years was 70%. In all subgroups the competing mortality was higher than the prostate

cancer mortality. Deferred treatment appears to be an acceptable treatment option for patients with

a tumor clinically confined to the prostate with a life expectancy of 10 years or less.

As you can see, there is great variability of results, but one thing seems to be obvious. Early disease

can be treated successfully with conservative therapy in older men with at least 10 years of life

expectancy. More aggressive prostate cancer results in a high rate of mortality when left untreated.

Age is an important factor in decision-making. If early disease is diagnosed at a young age there is

a high risk of dying from prostate cancer if treated conservatively. The bottom line is that men need

to evaluate their disease and understand the uncertainties of the present diagnostic methods before

they jump into any treatment or decide to do just plain observation.

Outside of the Scandinavian studies, Albertsen P et al.here in the U.S.A., have published a study

about the risks of surviving prostate cancer. "Competing risk analysis of men aged 55 to 74 years at

diagnosis managed conservatively for clinically localized prostate cancer." CONTEXT: The

appropriate therapy for men with localized prostate cancer is uncertain. Until results of clinical trials

are available, men and their physicians need guidance. OBJECTIVE: To estimate survival based on

a competing risk analysis stratified by age at diagnosis and histologic findings for men diagnosed

as having clinically localized prostate cancer and who were managed conservatively. DESIGN:

Retrospective cohort study. SETTING: Connecticut Tumor Registry. PATIENTS: A total of 767

men with localized prostate cancer diagnosed between 1971 and 1984, aged 55 to 74 years at

diagnosis, either not treated or treated with immediate or delayed hormonal therapy, and followed

up for 10 to 20 years after diagnosis. MAIN OUTCOME MEASURES: Estimates of the probability

of dying from prostate cancer or other competing hazards. RESULTS: Men with tumors that have

Gleason scores of 2 to 4, 5, 6, 7, and 8 to 10 face a 4% to 7%, 6% to 11%, 18% to 30%, 42% to 70%,

and 60% to 87% chance, respectively, of dying from prostate cancer within 15 years of diagnosis

depending on their age at diagnosis. CONCLUSIONS: Men whose prostate biopsy specimens show

Gleason score 2 to 4 disease face a minimal risk of death from prostate cancer within 15 years of

diagnosis. Conversely, men whose biopsy specimens show Gleason score 7 to 10 disease face a high

risk of death from prostate cancer when treated conservatively, even when cancer is diagnosed as

late as age 74 years. Men with Gleason score 5 or 6 tumors face a modest risk of death from prostate

cancer that increases slowly over at least 15 years of follow-up.

I wrote an e-mail query to Dr. Albertsen about this study, asking for guidance on what to tell a 55-

year-old man diagnosed with PCa with respect to conservative management because I meet some

of those in my support groups. Here is what he answered (I also requested authorization to publish

his response):

“Concerning your 55 year old man, I would recommend the following. If he has high-grade disease,

our study indicates that he has a high probability of dying from prostate cancer if he elects

conservative treatment. Therefore I would encourage him to do something. For men with low-grade

disease, this is a difficult problem. I would probably still recommend more aggressive treatment

because of the long life expectancy, but if the patient wanted to wait because of potency concerns

or something else, our study tries to estimate his probability of progression over a period of 15

years.”

In numerous conversations with those supportive of conservative treatment, the side effects of

treatment affecting QOL are almost always mentioned. The fact that treatment and conservative

treatment yield similar survival figures at 10 years is standard in such conversations. They tell me,

if you avoid treatment side effects and at the same time live the same number of years as those

undergoing damaging treatments, why would anyone with a sane mind undergo treatment?

The assumption that prostate cancer progression happens without inflicting any symptoms affecting

QOL is totally ignored in the above matrix. It never ceases to amaze me that such assumption is

invariably taken for granted. Prostate cancer progression can cause impotence, incontinence, urinary

blockage, kidney failure, bone metastasis, compression fractures and major organ metastatic

involvement causing major symptoms and eventually death.

The fact that diet seems to be involved in the development of clinical stages of prostate cancer is of

great preventive potential. Could the proper diet slowdown disease progression once diagnosed?

Several studies seem to support that fact although it is not known if the effect would apply to all

stages of the disease.

Going back to our historic recount, while those Scandinavian countries were exclusively applying

conservative management to prostate cancer, a more aggressive school of medicine developed here.

Surgery and radiation treatments came about as a result of this aggressive thought process. In looking

at the original attempts to improve survival with these aggressive methods, one has to conclude that

because of an ever-increasing mortality rate, nothing much was accomplished. The mortality rate

climbed steadily during this period. What is worse, studies demonstrated that the side effects of these

treatments were considerable. The medical profession, in its quest to promote survival in a few

individuals that might have benefited, caused a lot of pain in others; probably the majority, with

these ineffective methods. Remember, during this period both here and in Europe men were being

diagnosed with more advanced stages of the disease. The diagnostic methods then were DRE and

PAP, neither one very effective in establishing the presence of early disease. Bone scans did not have

or presently have the power to identify micrometastasis. Ultrasound was not available during the

early part of this period.

The historical lesson to learn from this in the U.S. is that conclusions derived from this period

represent attempts to treat more advanced disease. All early work done with hormonal suppression

for example is based on very advanced disease and the persistent conclusion as we all know, is that

hormonal suppression is effective for 18 to 24 months, then patients become refractive. Are the rest

of the conclusions derived from this period as mistaken as it is this example? Some are indeed.

There is no question that even though surgical methods have greatly improved because of better

equipment, anesthetics and surgical skills, urology uses a fudge factor to ameliorate side effects. Side

effects from surgery can't be ignored. Propensity for erectile dysfunction is high, very high.

Incontinence although improved, remains a possibility. Many men go into surgery without the

understanding of what it could do to them. This needs improvement and applies to many other less

invasive treatments. The use of robots and laparoscopic instruments count as recent improvements.

The same is true of more targeted methods of radiation therapy.

Those that proclaim the invincibility of treatments for prostate cancer always proclaim the

importance of survival over quality of life issues. It is therefore a question of preference, which has

to be addressed and well understood by the individual patient. On the other hand, opponents of

treatment tend to proclaim the suffering caused by treatment's side effects while ignoring the fact

avoidance conveys a high proportion of disease progression side effects. Urinary retention, uretric

blockade, impotence, incontinence, bone pain etc. are very prevalent during progression of prostate

cancer. Men need to understand all these facts in their decisions. In any way, it is not a clear-cut case

for one or the other.

In summary, all things said, there is no clear-cut, absolute, better way to treat or not treat prostate

cancer. It is still a very personal decision in a road full of obstacles. Awareness about all these

facts helps in defining our actual preferences. These are very personal things that dictate a

decision. What I believe is that the aggressive treatment system here is altering the natural course

of prostate cancer by reducing the mortality rate of the disease (at this time a 40% reduction since

PSA testing became available). Something has changed. The disease is treated earlier and "cures"

or freedom of disease have improved. The keyword is early and effective treatment. Let it be

surgery, new radiation modalities or early hormonal intervention. Something has changed. This

change translates to a reduced mortality rate for the past 20 years after a steady increase in the

previous 25 years. That is the current evidence....