3. Epidemiology, risk factors, prevention, and nutrition – Prostate Cancer
3.1 Epidemiology
In Germany, prostate cancer is the most common malignant tumor in men. The age-standardized disease rate has been largely constant since 2003 and declined between 2011 and 2016 [1]. The age-standardized incidence of prostate cancer varies worldwide. In Europe, a North-South divide is evident. For Sweden, age-standardized incidences of 175.2 diseased/100,000 men can be found, for Greece it is 34.2 diseased/100,000 men [2]. In Germany, 58,780 men were newly diagnosed with this cancer in 2016, corresponding to an age-standardized incidence of 91.6 per 100,000 population [1]. The highest incidence described worldwide is found in the United States (124.8/100,000), particularly in African-American men (185.4/100,000) [3]. Prevalence data based on autopsy findings are not available for Germany. From international studies, a prevalence between 70/100,000 (US African-American men) and 14/100,000 (Greek men) can be calculated for the age group between 60 and 70 years.
The mean onset age in 2016 was 72 years [1]. This cancer is an age-related disease. Before the age of 50, prostate cancer is rare. Prostate cancer represents the third most common entity among causes of cancer-associated death in men. 14,417 men died from the disease in 2016, corresponding to an age-standardized mortality rate of 19.5 per 100,000 population in Germany [1]. By 2050, the proportion of men over 60 in the German population is expected to grow to about 28 million (37 %), twice the current level [4]. Already by 2014, about half a million men were living with a diagnosis of prostate cancer made in the previous 10 years [4]. Due to demographic trends, both incidence and prevalence are expected to increase. This demographic change must be taken into account in the diagnosis, treatment, and follow-up of prostate cancer.
In particular, the proportion of early-stage diseases is increasing. This shift in stage is attributed to the testing for the tumor marker PSA (prostate specific antigen). Overall, approximately 40 % of the male population in Western industrialized countries carry the risk of developing prostate cancer during their lifetime, but only about 10 % become symptomatic and only 3 % die from the disease [5]. By far the most common cause of death in Western industrialized countries is cardiovascular disease [6]. Currently, the gap between incidence and mortality of prostate cancer (PCa) is still increasing. Presumably, the average life expectancy of men who die from prostate cancer is higher than the life expectancy of men who die from other causes. The impact of other diseases (comorbidities) on survival is proportionately greater than the impact of PCa itself for all age groups [7].
3.2 Risk factors
3.2.1 Risk factors for the occurrence of prostate cancer
Men shall be made aware that age is the most important risk factor for developing prostate cancer.
(For consequences with regard to early detection and screening, see chapter 4.1 “PSA and DRE in early detection/screening“).
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 4
- Consensus
- Consent (95%)
Men whose brothers and/or fathers have/had prostate cancer shall be made aware of an increased risk of over two-fold for developing prostate cancer in their lifetime.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 2++
- Consensus
- Strong consensus (98%)
- References
- [8] [9] [10]
Evidence tables (1)
3.2.1 EvT 3.2Re: Recommendation 3.1
This recommendation is based on epidemiological data from cancer registries, which show a strongly age-dependent incidence of prostate cancer, while the causes for the development of prostate cancer are essentially unknown. According to the Center for Cancer Registry Data, the incidences of this cancer in the 45-49 age group are 17.3/100,000 men in Germany (age-specific crude rate), while the peak incidence is 653.7/100,000 in the 70-74 age group and 692.7/100,000 men in the ≥ 85 age group [4]. According to the U.S. National Cancer Institute database “Surveillance Epidemiology and End Results“ (SEER), the incidence is close to 0 in the 30- to 34-year-old age group, 0.7/100,000 men in the 35- to 39-year-old age group, and, by contrast 905/100,000 in the 65- to 69-year-old age group [11].
No data are available from Germany on the autopsy-based prevalence of prostate cancer. For the USA, a higher prevalence has been shown in comparison to the only diagnosis-based SEER database. This increases from 8/100,000 in 20-30 year old white males to 83/100,000 in 71 to 80 year olds. For Greece, autopsies only identified prostate cancer from the 41-50 year old groups (3/100,000), the prevalence in 71-80 year olds in Greece is 31/100,000 [3].
Re: Recommendation 3.2
The association between a positive family history and the risk of developing prostate cancer has been adequately proven on the basis of two meta-analyses [8], [9]. The relative risk is 2.5 to 4.3% for any first-degree relative.
Other factors that increase the relative risk of prostate cancer are: younger age of affected family members, increasing genetic similarity to the affected family member and increasing number of individuals affected in the family.
Other possible risk factors
In addition to the above risk factors, there are a number of other factors associated with the occurrence of prostate cancer. None of the following associations were considered by the guideline group to be sufficiently convincing or clinically significant enough to develop a dedicated statement or recommendation.
- Dietary and socioeconomic factors
Globally, the incidence of prostate cancer shows a significant gradient from East to West, in favor of the Asian region; and within Europe, a North-South gradient can be seen in favor of Southern European countries (see chapter Epidemiology). This is associated with different dietary habits in the different countries, as well as socioeconomic factors [12], [13], [14].
Regarding diet, meta-analyses are available on cohort studies and case-control studies on a possible protective effect of phytoestrogens (especially soy) [15] and a diet rich in lycopene (found in tomatoes) [16], [17].
- Local inflammatory processes
In the currently accepted theory of the pathogenesis of prostate cancer, development of the disease can be divided into a nonandrogen-sensitive phase and an androgen-sensitive phase. In the first nonandrogen-sensitive phase, certain mutations as well as O2 radicals and carcinogens are believed to be responsible for the development of proliferative inflammatory atrophy. Chronic inflammatory responses are a major factor here. Additional epigenetic inactivation of certain genes then leads to prostatic intraepithelial neoplasia. From this point on, the development of prostate cancer is termed androgen-sensitive [18]. This theory supports the hypothesis that sexually transmitted diseases and the clinical picture of prostatitis are causally linked to the increased risk of prostate cancer development. If the risk for the presence of prostate cancer is assumed to be 1 in a healthy person, the odds ratio for any STD with respect to association with prostate cancer is 1.5 and 1.6 if prostatitis occurs [19], [20].
- Vasectomy
The results of a meta-analysis on the correlation between vasectomy and prostate cancer are inconsistent and insufficient to establish a sufficiently positive correlation. The authors themselves point out a possible bias in the highly heterogeneous studies [21].
- Diabetes mellitus
Unlike other tumor diseases, the presence of diabetes mellitus does not seem to increase the risk of developing prostate cancer [22]. On the contrary, meta-analyses actually show a lowered risk for prostate cancer in diabetics [23], [24].
- Obesity
Contradictory data exists on the influence of obesity on the development of prostate cancer, and these are from methodologically problematic studies [25], [26].
3.2.2 Testosterone replacement
In patients with hypogonadism with no clinically recognizable prostate cancer, testosterone can be replaced. To date, an increased risk of developing prostate cancer has not been demonstrated.
- Recommendation grade
- 0: offene Empfehlung (Option) bzgl. einer Maßnahme - verwendete Ausdrucksweise = kann
- Level of evidence
- 1+
- Consensus
- Consent (95%)
- References
- [27] [28] [29] [30] [31] [32] [33] [34] [35]
Evidence tables (1)
3.2.2 EvT 3.3If hypogonadism is detected, the patient shall undergo a digital-rectal examination and the PSA level should be determined before testosterone replacement is provided.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 4
- Consensus
- Consent (93%)
Re: Recommendation 3.3
Regarding the risk of prostate cancer in patients on testosterone replacement due to hypogonadism, our update search (2016) found three systematic reviews [33], [34], [35] whose results support the previous evidence ([27]). The meta-analyses each considered randomized placebo-controlled trials and show comparable incidences of prostate cancer diagnosed in treated patients and patients receiving placebo (Calof et al: 9.2 vs. 8.3 per 1,000 patient-years; Cui et al: cancer rate 1.57% vs. 1.60%; Boyle et al: summary odds ratio 0.87 (95% CI 0.30-2.50). Analyses of changes in PSA levels before and after testosterone replacement were also generally not significantly different. The frequency of biopsies being indicated is not suitable as an endpoint, according to the experts, because patients were presumably monitored more intensively. Data suggest that an increased risk of developing prostate cancer in hypogonadism patients on testosterone replacement has not been demonstrated to date. Although the median duration of treatment and observation of patients in the reviews is a maximum of three years, this period includes the vulnerable phase according to the assessment of the guideline authors, provided that the individual risk is dependent on testosterone replacement. Therefore, there are is no evidence against providing replacement therapy in indicated patients.
Re: Recommendation 3.4
The recommendation is based on expert consensus and results from an inverse argument. Since hormone blocking therapy is effective in the treatment of prostate cancer [36], it can conversely be concluded from an inverse argument that hormone replacement could stimulate occult prostate cancer. Therefore, the presence of prostate cancer should be excluded by DRE and PSA before starting hormone replacement.
3.3 Prevention and nutrition
Men shall be advised on a healthy lifestyle. This includes aspects of nutrition, physical exercise, and the psychosocial situation.
- Recommendation grade
- A: Starke Empfehlung für oder gegen ein Maßnahme - verwendete Ausdrucksweise = soll/soll nicht
- Level of evidence
- 4
- Consensus
- Consent (93%)
The use of 5-alpha-reductase inhibitors reduces the frequency of detection of prostate cancer and preneoplasia (high-grade prostatic intraepithelial neoplasia (PIN)). However, no evidence exists on the effect on tumor-specific mortality or all-cause mortality. PSA levels are lowered by 5-alpha-reductase inhibitors. In Germany, 5-alpha-reductase inhibitors are not approved for the prevention of prostate cancer.
Evidence tables (1)
3.3 EvT 3.6Re: Recommendation 3.5
The authors of this guideline are aware of the need for men to be provided with information on possible prevention strategies with regard to the development of prostate cancer and have therefore formulated the above recommendation. It is orientated on the recommendations of the American Cancer Society (ACS) guideline on “Nutrition and physical activity guidelines for cancer prevention" [41]. The recommendations are aimed at general cancer prevention but can also be applied to aspects of the prevention of other diseases, e.g. cardiovascular diseases. Although there are risk factors for prostate cancer (see above) or other cancers, the individual risk for each person cannot be determined. Therefore, it does not seem reasonable to give specific dietary advice for the prevention of prostate cancer, thus disregarding other dangerous diseases. This applies to other malignancies as well as to the morbidity and mortality of cardiovascular diseases, which remain in first place statistically speaking.
The more general recommendations also take into account the fact that dietary supplements such as vitamin E or selenium cannot be recommended for prevention, since in randomized-controlled trials neither the intake of vitamin E nor the intake of selenium, or the combination of both substances led to a statistically demonstrable reduction in the incidence of PCa [42]. In addition, special caution should be exercised in any preventive intervention, as these are healthy and symptom-free men.
The four main recommendations of the American guideline are:
a. Aim for a healthy weight.
b. Be physically active.
c. Maintain a healthy diet with an emphasis on plant-based products.
d. Reduce your alcohol consumption.
Re: a: Aim for a healthy weight.
- Ensure a healthy balance is maintained between energy intake (calories) and physical activity.
- Avoid or reduce obesity and try to maintain the healthy weight you have achieved.
- The healthiest way to reduce calorie intake is to reduce or eliminate extra sugar, saturated or trans fats, and alcohol. All of these foods are very high in energy and have too few or no essential food components such as vitamins, minerals, or fiber. Examples of these types of undesirable foods to avoid include fried or roasted foods, cookies, cakes, sugary products, ice cream, and sweetened soft drinks.
Re: b: Be physically active
- At least 30 minutes of moderate to vigorous physical activity in addition to normal daily activities at least five days a week is recommended for adults. 45-60 minutes is desirable.
- Moderate physical activity is defined as exertion of the type that occurs with fast walking (e.g., dancing, casual bicycling, golfing, playing volleyball, mowing the lawn, gardening). Vigorous physical activity requires the use of larger muscle groups, causes an acceleration of pulse and respiration, and increased sweating (e.g., jogging or running, aerobics, swimming, fast cycling, playing soccer, squash, cross-country skiing, carpentry, digging/yard work). An increase in everyday activity (climbing stairs instead of taking an elevator, walking or biking instead of driving a car, etc.) is equivalent to exercise.
Re: c: Maintain a healthy diet with an emphasis on plant-based products.
- Eat a variety of fruits and vegetables every day.
- Eat whole grains rather than products based on white flour.
- Limit your intake of meat products and red meat.
Re: d: Reduce your alcohol consumption
- Men should have no more than two alcoholic drinks per day. One drink (12 g alcohol) is equivalent to 0.33 liters of 5% beer, 0.04 liters (4 cl) of 40% liquor, 0.14 liters (14 cl) of 12% wine or sparkling wine, 0.07 liters (7 cl) of 20% liqueur/appetizer.
Re: Statement 3.6
Based on experimental and clinical observations, the Prostate Cancer Prevention Trial (PCPT) was initiated in 1993 [37]. This investigated the preventive effect of the 5-alpha-reductase inhibitor type-II, finasteride, in a prospective randomized double-blind trial. 18,882 healthy men over 55 years of age with a negative palpation exam and a PSA level below 3.0 ng/ml were randomized to a control arm with placebo, or a treatment arm with 5 mg finasteride. The study duration was seven years. A prostate biopsy was performed in case of PSA increase, abnormal palpation and at the end of the study.
At the time of early study termination, 24.1% fewer prostate cancers were found in the finasteride group (p < 0.0001), with statistically significantly fewer precancerous lesions (high-grade PIN) also found [38]. With regard to the Gleason score of the cancers, there were statistically significantly more tumors with a Gleason score of 7-10 in the intervention arm. After adjusting for age, race, family history, and PSA value, a relative risk of 1.28 with regard to the detection of cancers with a Gleason score of 7-10 was demonstrated to the disadvantage of the intervention group with finasteride (p=0.005). Follow-up studies in the following years indicate that the observed difference is due to the reduced prostate volume when treated with finasteride, thereby influencing the accuracy of the biopsy. When comparing the surgical specimen, the difference in detection of cancers of a high Gleason score was no longer statistically significant (Lucia et al. 2007 [43]). The present analyses are retrospective evaluations.
Finasteride is the first substance for which a preventive effect in prostate cancer has been demonstrated [39], [40], [44]. In another similarly designed, prospective randomized double-blind study, 8,231 patients with suspected prostate cancer were treated with the 5-alpha-reductase type I and II inhibitor dutasteride (REDUCE) for four years after a negative punch biopsy. Initial reports [45] suggest that the results are broadly consistent with those from PCPT. When weighing up the benefits and risks, it should also be borne in mind when considering possible preventive administration that the potential users are healthy and symptom-free men. 5-alpha-reductase inhibitors have not yet been approved for the prevention of prostate cancer.
Evidence tables
3.2.1 EvT 3.2
|
Studientyp |
Autoren, Jahr |
untersuchte Studien/ |
Welche Risikofaktoren oder präventiven Interventionen wurden geprüft |
Ergebnisse |
Bemerkungen |
LoE |
Literaturbelege |
|
Metaanalyse |
Taylor |
29 Fall-Kontroll-Studien aus systematischer Suche in Medline und Cinahl 1966 bis August 2004 |
Geschlechtskrankheiten und PCa-Risiko. |
OR für jegliche Geschlechtskrankheit 1,48 (95%CI 1,26-1,73) OR für Gonorrhoe 1,39 (95%CI 1,05-1,83) OR für Syphilis 1,42 (95%CI 0,76-2,64) OR für HPV 1,52 (1,12-2,06). |
17 Studien auch in Metaanalyse zu Sex und PCa-Risiko enthalten, hier keine Kohorten-Studien enthalten; Übereinstimmung mit Daten von Dennis 2002 bzgl. jeglicher Geschlechtskrankheit und Gonorrhoe, interessante starke Diskrepanz bzgl. Syphilis. |
2+ |
5-32 |
|
Metaanalyse |
Zeegers |
28 Studien (33 Publikationen) (8 Kohorten- und 20 Fall-Kontroll-Studien) aus systematischer Suche in Medline, Embase, Cancerlitbis Dezember 2002. |
Verwandtschaft |
RR für jeglichen erstgradigen Verwandten 2,53 (95%CI 2,24-2,85) RR für Söhne von betroffenen Vätern 2,17 (95%CI 1,90-2,49) RR für Brüder 3,37 (95%CI 2,97-3,83) RR für jeglichen erstgradigen Verwandten jünger als 65 Jahre 3,34 (95%CI 2,64-4,23) RR für jeglichen erstgradigen Verwandten älter als 65 Jahre 2,35 (95%CI 2,05-2,70) RR für erstgradige Verwandten, deren Vater oder Bruder im Alter von <65 Jahren diagnostiziert wurde 2,47 (95%CI 1,71-3,55) RR für erstgradige Verwandten, deren Vater oder Bruder im Alter von >65 Jahren diagnostiziert wurde 1,72 (95%CI 1,41-2,10) RR für einen erstgradigen erkrankten Verwandten 2,57 (95%CI 2,32-2,84) RR für zwei oder mehr erstgradige erkrankte Verwandte 5,08 (95%CI 3,31-7,79). |
Überlappung mit Publikation von Johns 2003 in 11 Studien, insgesamt mehr Studien eingeschlossen, Ergebnisse stimmen mit den Johns-Resultaten überein; deutliche familiäre Assoziation. |
2++ |
5-37 |
|
Metaanalyse |
Johns |
14 Studien (2 Kohorten- und 12 Fall-Kontroll-Studien) aus systematischer Suche in Medline 1966 bis August 2002. |
Verwandtschaft 1. Grades und PCa-Risiko |
RR für jeglichen erstgradigen Verwandten 2,5 (95%CI 2,2-2,8) RR für Söhne von betroffenen Vätern 2,5 (95%CI 2,1-3,1) RR für Brüder 3,4 (95%CI 2,9-4,1) RR für jeglichen erstgradigen Verwandten jünger als 65 Jahre 4,3 (95%CI 2,9-6,3) RR für jeglichen erstgradigen Verwandten älter als 65 Jahre 2,4 (95%CI 2,0-2,9). |
Verlässliche und gering bias-anfällige Daten, die für deutliche genetische Komponente sprechen. |
2++ |
5, 13-25 |
3.2.2 EvT 3.3
|
Studientyp |
Autoren, Jahr |
Untersuchte Studien/ Materialien |
Welche Behandlungen wurden geprüft |
Ergebnisse |
Bemerkungen |
LoE |
Literaturbelege |
|
Metaanalyse von RCTs |
Calof 2005
|
19 randomisierte placebo-kontrollierte Studien zur Behandlung von 651 + 433 Männern; Publikationen aus systematischer Suche in Medline, Old Medline, PubMed bis April 2004 |
Testosteron-Substitution bei Männern mit niedrigen oder niedrig-normalen Testosteron-Spiegeln versus Plazebo |
Einzige signifikante Unterschiede zwischen den Gruppen: erhöhte Wahrscheinlichkeit für „prostate event „ (Biopsien, PCas, IPSS>4, PSA >4 oder PSA-Anstieg >1,5) OR 1,78 (95%CI 1,07-2,95) erhöhte Wahrscheinlichkeit für Hämatokrit >50% OR 3,69 (95%CI 1,82-7,51) Keine erhöhte Wahrscheinlichkeit für PCa: OR 1,09 (95%CI 0,48-2,49)
|
Klinische Signifikanz von Zahlen, die auf einem mittleren Zeitraum (Therapie +follow-up) von 10 Monaten beruhen? Die meisten Männern werden sicher viel länger behandelt! Die Entstehung des Prostatakarzinoms nimmt wohl auch mehr als 10 Monate in Anspruch. |
1++ |
Amory 2004, Blackman 2002, Christmas 2002, Drinka 1995, Ferrando 2002, Ferrando 2003, Kenny 2002, Kenny 2004, Marin 1992, Munzer 2001, Sih 1997, Simon 2001, Snyder 1999, Snyder 1999, Snyder 2001, Tenover 1992, Wittert 2003 |
|
Artikel |
Studientyp |
Anzahl der Patienten |
Patientenmerkmale |
Intervention |
Vergleichsintervention |
Beobachtungszeitraum |
Outcomes |
Effekte |
Bemerkungen |
Evidenz-Niveau (SIGN) |
|
Gerstenbluth |
Retrospektive Studie |
54 |
Hypogonadale Männer mit ED, vor Therapie PSA<4ng/ml und DRE o.B. oder negative Biopsie |
Testosteron i.m. 2-4 wö |
keine |
Mittelwert: 30 Mo (2-82) |
PSA-Level vor und unter Therapie, Risiko für Prostata-karzinom |
Mittl. PSA vor Beh: 1.86 ng/mL (median 1.01 ng/mL, range 0.0–15.80), Mittl. PSA unter Beh: 2.82 ng/mL (median 1.56 ng/mL, range 0.–32.36 ) P<0,01 11,1% (6/54) mit Prostatabiopsie wegen PSA-Anstieg unter Therapie > 4ng/ml. 1x Diagnose ProstataCa |
Aufgrund der kleinen Fallzahl keine valide Aussage möglich |
2- |
|
Hajjar |
retrospektive Kohorte-studie |
58 |
Hypogonadale Männer ohne Prostata-Karzinom aus Sexualsprechstunde einer US-Klinik |
Testosteron i.m. (31 Pat.) |
KeineTestosteron-Substitution (27 Pat.)
|
2/3 der Probanden über 2 J |
Vergleich der Libido und Serumwerte beider Gruppen nach 2 Jahren (u.a. PSA), Langzeit-Verträglichkeit der Hormonsubstitution |
Vergleich Serumwerte nach 2 Jahren: signifikant höherer Hämatokrit in Substitutionsgruppe Kein signifikanter PSA-Unterschied (diesem Vergleich liegt eine Zahl von 26 Substitutionspatienten und 15 Kontrollen zu Grunde) Libido-Veränderung stärker in Substitutionsgrupppe (es ist anzunehmen, dass die Kontrollgruppe gar keine Libidostörungen hatte und deshalb auch die Testosteronsubstitution nicht wollte) Plazebo-Effekt? 31% Therapie-Abbrecher in der Substitutionsgruppe wegen NW |
Viel zu kleine Gruppen für valide Aussagen, statistisch unterpowert!! Keine Randomisation, keine Angabe von Gründen, auf Grund welcher Beschwerden Studien-Pat. überhaupt Testosteron erhielten. |
2- |
|
Marks 2006 |
RCT |
44 |
Hypogonadale Männer (Gesamt-Testosteron £ 300ng/dl |
alle 2 Wochen Testosteron-Enanthat 150 mg über 6 Monate |
Placebo i.m. |
6 Mo |
Primär: Prostate-tissue-androgen-level
Sekundär: Prostatabezogene klinische Parameter: Histologie, Biomarker, epitheliale ‘cell gene expression’ (u.a.PSA) |
1. Bei Hypogonadalen beeinflusst die exogene Testosteron-Substitution das gewebespezifische Testosteron-Milieu in der Prostata nicht signifikant 2. Für Behandelte gibt es wie für Nicht-Behandelte ein spontanes Prostatakarzinomrisiko von 1/7 3. PSA-Level stiegen in beiden Gruppen statistisch signifikant an PSA TRT vor Beh.: 1.55 (0.30-5.80) Nach Beh: 2.29 (0.40-7.10) p<0,001 PSA Placebo vor Beh: : 0.97 (0.10-2.50) Nach Beh: 1.10 (0.02-6.90) P=0,006 |
Zu kleine Studiengruppen, um anhand der erhobenen Parameter eine Aussage über das Prostatarisiko unter TRT zu machen! Auch in Bezug auf Kurzzeittherapie. Dieser RCT war geplant als short-term efficacy-trial für größeren Safety-RCT (gepl. N=6000) mit viel längerer Nachbeobachtung! |
1- |
|
Rhoden |
retrospektive Kohorten-studie |
75 |
Hypogonadale Männer davon: 20 mit highgrade PIN, der Rest ohne, Durchschnittsalter 59,6 J |
Testosteron-Substitution |
Keine, Vergleich zwischen Männern mit PIN (20) und ohne PIN (55) |
1 J |
PSA, DRE-Befund, bioptisches PCa (Biopsie bei allen PIN-Patienten, bei allen Patienten mit PSA-Anstieg um >1 oder auffälliger DRE) |
Durchschnittl. PSA-Werte baseline in beiden Gruppen nicht signifikant verschieden (1,53 bzw. 1,49) Durchschnittl. PSA-Anstieg nach 1 J in beiden Gruppen nicht signifikant verschieden (0,25 bzw.0,33) in highgrade PIN-Gruppe entwickelte 1 Proband ein PCa unter der Testosteron-Substitution (ein weiterer Patient mit auffälligem PSA verweigerte Biopsie), in Gruppe ohne PIN kein PCa (vier Biopsien mit negativem Ergebnis) |
Sehr kurzes Follow-up, kleine Fallzahlen mit fraglichem statistischen Wert und ohne Generalisierbarkeit. |
2- |
|
Wang |
Fallserie (prospektiv erhobene Daten) |
123 |
Hypogonadale Männer (49 primär, 27 sekundär, übrige „symptomatisch-altersbezogen“ oder normogonadotroper Hypogonadismus), Durchschnittsalter 51,4 J. |
Testosteron transdermal in 3 verschiedenen Dosen. |
keine |
42 Mo |
Hormonspiegel, Muskelkraft, Knochendichte, sex. Funktion, Körpergewicht, PSA-Level. |
Signifikanter Anstieg des durchschnittlichen PSA-Levels aller Probanden von 0,85 auf 1,11 nach 6 Monaten, dann kein weiterer signifikanter Anstieg. 7 Probanden mit PSA-Anstieg >5,5, aber Biopsie nur bei 4 Probanden: 3 PCa |
Feasibility-Studie zur Anwendung von Testosteron-Pflaster, PCa kein primärer Endpunkt, kein Vergleichskollektiv, selbst nach Angaben der Autoren erlaubt die Studie keine Aussage zum PCa-Risiko unter Testosteron-Substitution. |
3
|
|
Zitat |
Population |
Intervention |
Suchstrategie, Studien-Einschlusskriterien |
eingeschlossene Studien |
Ergebnisse |
methodische Validität |
LoE |
|
Boyle P. Endogenous and exogenous testosterone and the risk of prostate cancer and increased prostate specific antigen (PSA): a meta-analysis. BJU Int 2016. |
mean age/ study: 39 - 80 y |
testosterone replacement therapy vs. placebo |
Cochrane library, PUBMED until May 2015 (+ reference lists) |
27 studies |
change of PSA level: |
1. a priori Design - x |
1- |
|
Kang DY. |
mean age/ study: 44 - 72 y |
testosterone replacement therapy or androgen replacement |
Medline, Cochrane |
15 studies |
change of PSA level (9 studies): |
1. a priori Design - x |
1++ |
|
Cui Y. |
median age / study: 52 - 79 y |
testosterone replacement therapy vs. placebo |
Medline, Embase, |
22 studies |
short-term TRT: |
1. a priori Design - x |
1++ |
3.3 EvT 3.6
|
Artikel |
Studientyp, prospektiv/ |
Anzahl der Patienten |
Patientenmerkmale |
Präventive |
Follow-up |
Outcome Parameter |
Ergebnisse |
Bemerkungen |
Evidenz-Niveau (SIGN) |
|
Thompson 2003 |
RCT, multizentrisch |
18.882 (9.060 ausgewertet) |
Kein Anhalt für PCa (DRE, PSA) |
Finasteride (5 mg/d) vs. keine Prävention |
7 J |
Inzidenz bioptische gesichertes PCa, Gleason-Score, Nebenwirkungen. |
PCa-Inzidenz: 803 von 4368 Finasteride-Patienten (18,4%) 1147 von 4692 Placebo-Patienten (24,4%) = 6% Reduktion durch Finasteride = 24,8%ige Reduktion des relativen Risikos (signifikant). Inzidenz höhergradiger Tumoren (Gleason 7,8,9,10): 280 von 4368 Finasteride-Patienten (6,4%). 237 von 4692 Placebo-Patienten (5,1%) = RR für höhergradige Tumoren 1,67 für Finasteride-Patienten (signifikant). Inzidenz von erektiler Dysfunktion, Libidoverlust, Gynäkomastie höher in Finasteride-Gruppe. Inzidenz von Harndrang, höherer Harnfrequenz, Prostatitis, Harnwegsinfektionen und Harnverhalt höher in Placebo-Gruppe. |
Größter existierender Prävention-Trial – der Reduktion der PCa-Inzidenz steht die erhöhte Zahl höhergradiger PCa ’s in der Finasteride-Gruppe gegenüber; mögliche Erklärungen: 1. selektive Unterdrückung niedrig-gradiger Tumoren, 2. morphologische Veränderung der PCa-Zellen durch Finasteride. |
1++ |
|
Thompson 2007 |
RCT |
18.882, davon 4.886 auswertbar in Placebo-Gruppe und 4.568 in Finasteride-Gruppe |
Keine An-zeichen von PCa (weder PSA noch DRE) |
Finasteride (5 mg/d) vs. keine Prävention |
7 J |
High-Grade intraepiethliale Neoplasie (PIN) in Biopsie |
High-grade PIN ohne invasives PCa in 276 Patienten der Finasteride-Gruppe und 347 in der Placebo-Gruppe (p=0,04). High-grade PIN mit invasivem PCa in 144 vs 233 in Finasteride- bzw. Placebo-Gruppe (p=0,0004). High-grade PIN mit oder ohne invasives PCa in 420 vs 570 in Finasteride- bzw. Placebo-Gruppe (p<0,001).
|
Leicht unterschiedlich hohe drop-out-Raten in beiden Therapiearmen (48% in Placebo-Gruppe und 52% in Finasteride-Gruppe). |
1++ |
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