Feeds:
Posts
Comments

Posts Tagged ‘co-morbidities’

JUNE 28: NEW PROSTATE CANCER INFOLINK: A study on the possibility that lifestyle modification will help cancer survivors to avoid the risks that they are at for second malignancies, other co-morbidities, and accelerated functional decline seems worthwhile. READ MORE>

Read Full Post »

JUNE 13: NEW PROSTATE CANCER INFO-LINK: A new study provides substantial evidence there is now very low  risk of death in radical prostatectomy. But there is clearly still a greater risk for mortality in older patients with one or more co-morbidities, which increases the necessity for great care in determining whether surgery is an appropriate treatment option, particularly in the case of patients older than 75, in whom their life expectancy should be a key factor in determining whether any form of invasive treatment is appropriate by comparison with expectant management techniques. READ MORE>

Read Full Post »

PROSTABLOG NZ: The American Urological Association’s newly revised PSA best practice guidelines have just been posted on the association’s website and there are a couple of significant changes.

The document says these are:

  1. The age for obtaining a baseline PSA has been lowered to 40 years.
  2. The current policy no longer recommends a single, threshold value of PSA which should prompt prostate biopsy. Rather, the decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and co-morbidities.

Other key points include:

  • Recently published trials show different results with regard to the impact of prostate cancer screening on mortality, [but] both suggest that prostate cancer screening leads to over-detection and over-treatment of some patients. Therefore, the AUA strongly supports that men be informed of the risks and benefits of prostate cancer screening before biopsy and the option of active surveillance in lieu of immediate treatment for certain men newly diagnosed with prostate cancer.
  • An analysis of autopsy studies has shown that approximately one in three men over the age of 50 years had histologic evidence of prostate cancer, with up to 80% of these tumours being limited in size and grade and, therefore, clinically insignificant.
  • A recent study of incidental prostate cancer diagnosed in organ donors found prostate cancer in 1 in 3 men age 60-69, and this increased to 46% in men over age 70 (Yin 2008). Fortunately, the lifetime risk of prostate cancer death is only about 3% (Ries 2008).
  • Some studies have found that a large proportion of patients diagnosed with clinically localized prostate cancer who did not receive early aggressive treatment still had favourable clinical outcomes and normal life expectancies (Albertsen 1995, Coley 1997, Klotz 2006).
  • The general disparity between the high prevalence of prostate cancer and the relatively low lifetime risk of prostate cancer death highlights the importance of distinguishing those cancers that are destined to cause significant illness and premature death from those that are not.
  • The use of PSA testing for the early detection of prostate cancer remains controversial, however, owing to its biological variability, high prevalence, and the strong evidence for over-diagnosis and over-treatment (Schroder 2009, Woolf 1995).
  • There has been a gradual but steady decline in prostate cancer mortality in the US of approximately 30% (Ries 2008). This trend began fairly soon after the introduction of PSA testing, there is evidence from statistical modelling studies that PSA testing has played a role (Hankey 1999, Feuer 2004, Etzioni 2008b).
  • Screening with PSA is responsible for a substantial shift towards detection of prostate cancer at earlier stages (Etzioni 2008a). Moreover, recent evidence from both a randomized trial in Sweden and a well-controlled cohort study in the US indicate that active treatment of clinically localized prostate cancer may reduce prostate cancer specific mortality (Bill-Axelson 2005, Wong 2006).
  • These conclusions have not been supported in all studies, however. A recent randomized trial of prostate cancer screening with PSA, the European Randomized Study of Screening for Prostate Cancer (ERSPC), demonstrated only a modest 20 percent relative reduction in prostate cancer deaths among those screened when compared to those that were not at nine years (Schroder 2009).
  • Similarly, the Prostate, Lung, Colon, and Ovary Trial of the NCI found no difference in prostate cancer deaths at 7-10 years of follow-up when comparing those screened to those that were not (Andriole 2009).The results of this study should be reviewed with some caution as acknowledged by the authors. Many men (approximately 44%) in the experimental and control groups had undergone PSA testing previously, before entry into the trial.Such pre-screening could have eliminated some cancers, which would have been detectable in the randomized population.
  • …follow-up for both trials may not be long enough to detect a benefit for screening given the protracted natural history of many prostate cancers.
  • Thus, it is still not clear that prostate cancer screening results in more benefit than harm. Longer follow-up in these randomized trials will be necessary to address the balance of benefits and harms of screening for prostate cancer.It should be pointed out that these trials used a single cut-point of serum PSA to prompt a biopsy, a different strategy than is proposed in these updated guidelines.
  • Given the uncertainty that PSA testing results in more benefit than harm, a thoughtful and broad approach to PSA is critical. Patients need to be informed of the risks and benefits of testing before it is undertaken. The risks of over-detection and over-treatment should be included in this discussion.

Because there is now evidence from a randomized, controlled trial regarding a mortality decrease associated with PSA screening, the AUA is recommending PSA screening, as proposed in this document, for well-informed men who wish to pursue early diagnosis.

  • The AUA recommends that all discussions of treatment options include active surveillance as a consideration, since many screen-detected prostate cancers may not need immediate treatment.
  • Studies have shown that long-term survival is considerably diminished in men diagnosed with prostate cancer that has already spread beyond the confines of the prostate to regional lymph nodes or to more distant sites.
  • There is currently no universally accepted definition of clinically significant or insignificant prostate cancer. 
  • More recently, investigators have shown that the number of biopsies showing cancer, as well as the extent of cancer in individual cores, may both be helpful in assessing the likelihood of insignificant disease (Antunes 2005, Ochiai 2005, Cheng 2005).
  • Tumour grade appears to be the strongest prognostic factor, although such assessments, even from multiple biopsy specimens, are subject to sampling errors (Stamey 1993, Epstein 1994).
  • No currently available non-invasive imaging method can consistently and reliably measure tumour volume.
  • Accumulated data suggest that combinations of preoperative data, including PSA level, clinical stage, and Gleason score from biopsy, can significantly enhance the ability to predict actual pathologic stage and outcome following treatment (Kattan 1998, Cooperberg 2005, Partin 1997, Partin 2001).
  • Evidence from three uncontrolled studies suggests that combining both tests (digital rectal examination and PSA) improves the overall rate of prostate cancer detection when compared to either test alone (Bretton 1994, Muschenheim 1991, Richie 1993). Recent evidence from the ERSPC found that DRE did not improve prostate cancer screening over PSA testing alone, however (Gosselaar 2006).
  • The widespread use of PSA testing has caused many men to be diagnosed with prostate cancer much earlier in their lives when compared to the pre-PSA era.
  • Unfortunately, prostate cancer poses an epidemiologic conundrum. Recent studies have shown that the lifetime risk of prostate cancer diagnosis is about 16%, but the lifetime risk of dying from this disease is only 3.4% (Ries 2008).
  • …men, whose PSA was previously thought to be ‘normal’, 15% were found to have cancer. However, it remains unknown what proportion of these cancers includes clinically significant disease (Schroder 2008a). A significant proportion of men harbour small foci of latent prostate cancer, many of which are not destined to become clinically significant.
  • Widespread, repeated PSA testing has raised a concern over the possible over-detection of prostate cancer. Over-detection refers to the ability of a screening test to identify a condition that would have remained silent and caused a patient no morbidity during his lifetime.
  • This is in contrast to over-treatment, although in the United States these two are unfortunately often linked, in some cases to the detriment of patient quality of life. For example, despite a decrease in risk category of disease at the time of diagnosis, approximately 90% of men still elect some type of intervention, including surgery, radiation therapy, or androgen deprivation (Cooperberg 2007).
  • …the likelihood of detecting smaller, more indolent tumours, that will never progress to clinical significance, remains high. Draisma et al have estimated that at age 55 years, PSA testing results in an over-detection rate of 27% (Draisma 2003). By age 75, the rate of over-detection increases to 56%. Similar concerns have been raised by others (Ciatto 2005, Etzioni 2002).
  • In men with clinically significant prostate cancers, complications associated with treatment are most often considered acceptable if the treatment prolongs life or reduces morbidity from the disease.
  • In men who harbour indolent disease or disease that is not likely to become symptomatic during the patient’s lifetime, however, any morbidity from treatment likely lowers quality of life and should be considered a potential harm associated with PSA testing.
  • …short term fluctuations in PSA…can lead to inappropriate biopsy and potential over-detection of indolent or small-volume cancer. Laboratory variability can range from 20-25% depending upon the type of standardization used.
  • One way to improve sensitivity of PSA is to use a lower threshold value for all men. Doing so improves the likelihood of detecting cancers, including some aggressive tumours that are present at PSA levels below 4.0 ng/mL, but also risks the detection of clinically-insignificant tumours.
  • Another way to improve sensitivity is to adjust the “threshold” PSA level to a lower value for younger men (age-specific or age-adjusted PSA). Men in their 40s that are cancer-free, for example, most likely have a serum PSA value of 2.5 ng/mL or less (Oesterling 1993a).
  • Several studies suggest that lower PSAV thresholds of 0.4 ng/ml per year may improve prostate cancer detection for younger men and for those with PSA levels below 4.0 ng/ml (Moul 2007, Loeb 2007, D’Amico 2004, Carter 2006).
  • To correctly measure PSAV (PSA velocity or rate of change), use of at least three PSA values over a time period of at least 18 months is recommended (Carter 2006, D’Amico 2004).
  • Estimating PSAV with values spread over a longer interval is problematic because when significant prostate cancer is present, PSA increases exponentially and a linear estimate of PSA slope is less valid.
  • Both age-specific PSA and age-specific PSAV will increase the number of cancers detected, and both will also increase the number of younger men undergoing biopsy. However, when added to total PSA, PSAV was not shown to be a useful independent predictor of positive biopsy, in the ERSPC and PCPT trials, or in other analyses (Etzioni 2007, Wolters 2008, Vickers 2009).
  • Only about one prostate biopsy in four currently finds prostate cancer (Arcangeli 1997). One method to improve PSA specificity is to set higher “normal” PSA levels for older men. Because serum PSA tends to increase with age, the use of higher “normal” levels for older men results in fewer biopsies (Richardson 1997).
  • All four methods – age-adjusted PSA, free/total PSA ratio, complexed PSA, and PSA/TZPSAD density – can be used to improve the sensitivity (detect more cancers) and/or specificity (avoid unnecessary biopsies) of PSA testing. To what extent such methods will do either is heavily dependent on the cut-points used and the subset of PSA levels to which they are applied.
  • Because of potential tradeoffs between sensitivity and specificity, there is at present no consensus on optimal strategies for using the different modifications of PSA testing.
  • The Prostate Cancer Prevention Trial demonstrated that there is no safe PSA value below which a man may be reassured that he does not have biopsy-detectable prostate cancer. Instead, there is a continuum of risk at all values, with higher values of PSA associated with a higher risk of prostate cancer.

Because of this, the AUA is not recommending a single threshold value which should prompt prostate biopsy. The decision to proceed to prostate biopsy should be based primarily on PSA and DRE results, but should take into account multiple factors, including free and total PSA, patient age, PSA velocity, PSA density, family history, ethnicity, prior biopsy history and co-morbidities.

  • It should also be acknowledged that there are likely to be other serum markers, which will, in the future, either replace or complement the use of serum PSA for prostate cancer early detection. (Varambally 2008, Vickers 2008, Makarov 2009, Sreekumar 2009, Chun 2009, Fujita 2009).
  • There is no PSA level below which a man can be reassured that prostate cancer does not exist. Because of this, the use of risk assessment tools is an attractive alternative to a traditional threshold value.
  • The proportion of men with higher volume cancers, extraprostatic disease, higher grade disease, and biochemical failure after treatment all increase as the PSA level increases (Loeb 2006a, Thompson 2006a, Catalona 1997, Rietbergen 1999, Partin 1993, Han 2001, Roehl 2004).
  • …even after accounting for age, race, grade, stage, and year of surgery, the pre-operative PSA level is significantly associated with the risk of biochemical failure after surgical treatment of prostate cancer; for each 2-point increase in PSA level, the risk of biochemical progression increases by approximately 2-fold (Freedland 2005b).
  • Numerous investigators have found that the integration of clinical stage, histologic tumour grade, and PSA level can further refine the ability to predict outcomes after treatment for prostate cancer.
  • Based on a randomized trial of prostate cancer screening, there appears to be a modest reduction in prostate cancer mortality among those screened when compared to those that are not (Schroder 2009).
  • In another screening study, there was no difference in prostate cancer mortality when comparing men that were and were not screened (Andriole 2009).
  • However, there is a large amount of over-diagnosis and over-treatment associated with screening (Schroder 2009, Andriole 2009) and at this point it is not possible to state that screening is associated with more benefit than harm.
  • Decisions regarding early detection of prostate cancer should be individualized, and benefits and consequences should be discussed with the patient before PSA testing occurs. Not all men are appropriate candidates for screening efforts for this disease.
  • Although family history of prostate cancer confers a higher risk of prostate cancer diagnosis, it is not associated with an increased risk of high-grade disease.

Early detection and risk assessment of prostate cancer should be offered to asymptomatic men 40 years of age or older who wish to be screened with an estimated life expectancy of more than 10 years.

  • Among men in their 40s and 50s, a baseline PSA level above the median value for age is a stronger predictor of future risk of prostate cancer than family history or race (Fang 2001, Loeb 2006b).
  • One way to identify this high-risk group of men with a PSA level above the median value in their 40s is to obtain a baseline PSA level at age 40, and then to determine future screening intervals based upon this number. Men in their 40s with a PSA value above the median (0.6 to 0.7 ng/mL) are at higher risk for prostate cancer (Fang 2001, Loeb 2006b).
  • Although prostate cancer prevalence is low among men younger than 50, there are a number of reasons to offer early detection prior to age 50:
  1. First, the age adjusted mortality rate for prostate cancer per 100,000 males (all races) between ages 55 and 64 is 18 (Ries 2008). Since death from prostate cancer occurs, on average, 15 to 20 years after diagnosis of an early cancer (Horan 2000, Johansson 2004), men dying at age 55 to 64 likely could have been cured by diagnosis and effective treatment prior to age 50.
  2. Second, when compared to men more than age 50, younger men are more likely to have curable prostate cancer (Carter 1999, Smith 2000, Khan 2003).
  3. Third, measurement of the PSA level is a more specific test for cancer in younger men compared to older men because prostatic enlargement is less likely to confound the interpretation of the estimated PSA value (Morgan 1996).
  4. Fourth, infrequent testing of men in their 40s and after age 50 might reduce prostate cancer mortality and the cost of screening when compared to annual testing beginning at age 50 (Ross 2000).
  5. Finally, given the relationship between PSAV and death from prostate cancer decades later (Carter 2006), establishing baseline PSA values against which to compare future PSA measurements after age 50 could help identify those men with life threatening prostate cancer at a time when cure is still possible.
  • Recent analyses from sections of the European Randomized Study of Prostate Cancer Screening suggest that most cancers detected at two to four years after an initial screen (1st round) will be curable (Hugosson 2003, van der Cruijsen-Koeter 2003, Hoedemaeker 2001, Postma 2004, Hugosson 2004)
  • Because of the long natural history of prostate cancer and the ability of PSA screening to uncover most cases of advanced life-threatening cancer at the initial screen, frequent screening will contribute to the cumulative risk of undergoing a biopsy and appears unnecessary for most men.
  • Because of the long natural history of most prostate cancers and competing causes of death (Albertsen 2005a), the benefits of screening may decline rapidly with age (Ross 2005, Holmberg 2006).
  • The incidence of high-risk prostate cancer in fact increases with age, accounting for 43% of cancers diagnosed in men >75 vs. 25% among men <75 (Konety 2008).Additionally, there must be a distinction made between screening for prostate cancer and treatment of prostate cancer. Diagnosis of prostate cancer in this age group may be informative for a man’s overall health, but may never require treatment beyond active surveillance.
  • Conversely, men with aggressive prostate cancer in this age group should not be denied the opportunity for the diagnosis and treatment which could affect their length and quality of life.
  • Once the concept of diagnosis automatically prompting treatment is dispelled, the issue of prostate cancer screening in any age group becomes less controversial.
  • The early biochemical (PSA) detection of recurrence after definitive local therapy may prompt further treatment.The optimal strategy for such adjunctive therapy, including time of initiation, remains uncertain, and it is the focus of ongoing clinical trials and study.
  • A detectable PSA following radical prostatectomy is associated with eventual clinical disease recurrence in some, but not all patients. It may also be due to the presence of benign glands (Furusato 2008).
  • The utility of “ultra-sensitive” PSA testing has not been established as yet. Although its use seems to distinguish between those who are less likely and those who are more likely to recur, there may be considerable variability and inconsistency of results at low PSA levels (Shen 2005, Taylor 2006).
  • Serum PSA should fall to a low level following radiation therapy, high intensity focused ultrasound and cryotherapy and should not rise on successive occasions.A consistently rising PSA level usually, though not always, indicates cancer recurrence.
  • The number of rises needed to define a failure has been a matter of debate, but a consensus is emerging in support of the American Society for Therapeutic Radiation and Oncology (ASTRO) definition of failure: three successive rises above nadir (American Society for Therapeutic Radiology Oncology, 1997).More recently it has been recognized that this end-point is relevant only for external beam radiotherapy and even then it is easily confounded by biological variability.
  • The change in PSA following interstitial prostate brachytherapy is complex. Over the first year, the PSA level declines, then rises again in the second or third year in up to 40% of cases, only to fall back to much lower values by year four (Critz 2000, Merrick 2003, Stock 2003).Although these rises (or “benign bounces”) are generally small (<0.8 ng/mL), they can, on occasion, be as high as 10.0 ng/mL, and they may last for 6 to 18 months. Their cause is uncertain, but they may correspond to infarction of the prostate occurring as a late vascular effect of the radiation.The principal concern regarding the benign bounce is that it may be confused with failure and lead to the initiation of unnecessary additional therapy. Ironically, bounces may actually predict a particularly good ultimate outcome (Patel 2004). By the fifth year after interstitial prostate brachytherapy, the PSA level is <0.6 ng/mL in 90% of patients who are clinically disease free. The median PSA level of these patients is <0.1 ng/mL (Zelefsky 2006).
  • A Consensus Committee convened in Phoenix in 2005 arrived at the following conclusions: that any rise in PSA level of 2.0 ng/mL or more, over and above the nadir, predicted true failure with great sensitivity and specificity after both external beam radiotherapy and interstitial prostate brachytherapy, irrespective of whether either of these treatments was accompanied by androgen deprivation.
  • …data clearly support the prognostic importance of the value of the PSA nadir after androgen deprivation therapy and suggest that careful PSA monitoring after the initiation of such therapy can effectively identify those patients with a poor prognosis.
  • For patients with hormone-refractory disease (defined as disease progression despite castrate levels of testosterone), the relationship between PSA decline and prognosis remains controversial. Despite multiple studies indicating that PSA declines of >50% correlate with survival (Small 2001, Oudard 2005, Sartor 1998), large well-controlled studies have shown mixed results (Tannock 2004, Petrylak 2004, Armstrong 2007).
  • For patients with a rising PSA level after surgery or radiation for localized prostate cancer, the estimate of total PSA alone is an imperfect predictor of a positive bone scan.
  • Excellent data now indicate that patients with a long PSADT (>15 months) have a low likelihood of prostate cancer-specific mortality over a 10 year period (Freedland 2005a), and active surveillance may be considered for those with a life expectancy of <10 years.

Read Full Post »