The diagnosis of a low grade prostate cancer in men diagnosed at younger age (e.g. below 55- year) poses an important clinical dilemma, i.e. to treat immediately or to defer treatment. Their long life expectancy would on the one hand argue for immediate treatment, given the unknown risk of progression of disease over time, on the other hand deferred treatment would be very attractive, given the phase in their life.
The same low risk tumour found in a men > 55 year would nowadays often lead to enrollment in an active surveillance protocol, whereas a USA survey published in 2012 showed that about 95% of men < 50 years diagnosed with a Gleason score 6 prostate cancer between 2001 and 2005 had opted for immediate treatment (1). Clinical outcome data after immediate therapy of a low risk prostate cancer demonstrate a similar good prognosis for young men and older men. However, most studies agree that the prognosis after treatment of a high risk prostate cancer is significantly worse for younger men (2,3). To our knowledge, there are no outcome data available specifically for men below 55 years with low risk prostate cancer who enrolled into active surveillance. Therefore, the reluctance of clinicians and younger men with low risk prostate cancer to defer their treatment is understandable.
In literature a few different terminologies for prostate cancers identified in younger men are being used, such as young-onset, young-age and early-onset prostate cancer. We propose to restrict the terminology early-onset to those prostate cancers that became clinically detectable (at least DRE-positive) in men below the age of 55 years, to separate them from PSA detectable incidental prostate cancers. A prostate cancer manifesting symptoms in men below age 55 is a very different disease than a prostate cancer detected by PSA testing. Autopsy studies have shown that 20-30% of men living in the USA and Middle and Northern Europe harbor a prostate cancer, the vast majority a Gleason scores 6 (3+ 3) prostate cancer (4). In mandatory or population-based PSA screened populations of young age men, nearly all detected prostate cancers are Gleason score 6 (3 + 3) prostate cancers, whereas prostate cancers detected in young men by ad hoc PSA testing much more often contain high grade cancer (5,6).
In contrast to early-onset prostate cancer the term young-age prostate cancer would encompass all prostate cancers identified in men below the age of 55 years. We anticipate that this distinct terminology would lead to an improved comparison of more homogenous groups of young-age prostate cancers.
An important question is whether young-age prostate cancers are biologically and genetically different than prostate cancers diagnosed at older age. Several findings suggest that this is the case for a proportion of young-age prostate cancers:
1) Men at young age with a prostate cancer diagnosis may harbor more often a familial prostate cancer, since familial prostate is detected usually 6 to 7 years earlier than sporadic disease and the risk of (familial) prostate cancer increases when a family member develops the disease at a younger age (7).
2) Particularly in early-onset prostate cancers a germline aberration is more frequent than in older men diagnosed with prostate cancer. BRCA2 carriers had an estimated 23-fold increased risk of prostate cancer for men aged less than 55 and these cancers often present with aggressive features, such as intra-ductal carcinoma, extra-prostatic extension and lymph node metastases (8). Nevertheless, BRCA2 carriers represent just 2% of the population of young men with a diagnosed prostate cancer versus an estimated 0.5-0.7% in the general population.
3) The TMPRSS2-ERG fusion gene is more common in young-age prostate cancer (about 60%) versus older age prostate cancer (about 40%). This would point at a more activated androgen-androgen receptor axis in young-age prostate cancers (9). More recently, amplification of the L-Myc gene appeared to be age-dependent, occurring more frequently at younger age (10). The latter finding, however, needs further confirmation in a separate population, comprising more young-age prostate cancers.
Particularly, the higher frequency in young-age prostate cancer patients of particular molecular-genetic alterations would suggest a distinct pathogenesis and biological behavior. More study of young-age prostate cancers is warranted to obtain solid evidence for potential benefits of a tailored therapeutic approach of these patients.
References:
1. Sidana A, Hernandez DJ, Feng Z, Partin AW, Trock BJ, Saha S, Epstein JI. Treatment decision-making for localized prostate cancer: what younger men choose and why. Prostate. 2012 Jan;72(1):58-64.
2. Lin DW, Porter M, Montgomery B. Treatment and survival outcomes in young men diagnosed with prostate cancer. Cancer 2009; 115:2863–71.
3. Kimura T, Onozawa M, Miyazaki J, Matsuoka T, Joraku A, Kawai K, Nishiyama H, Hinotsu S, Akaza H. Prognostic impact of young age on stage IV prostate cancer treated with primary androgen deprivation therapy. Int J Urol. 2014; 21(6):578-83.
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6. Ranasinghe W, Kim S, Lawrentschuk N, et al. Population-based analysis of prostate-specific antigen (PSA) screening in younger men (<55 years) in Australia. BJU Int 2014;113:77–83.
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8. Edwards SM, Evans DG, Hope Q, Norman AR, Barbachano Y, Bullock S, Kote-Jarai Z, Meitz J, Falconer A, Osin P, Fisher C, Guy M, Jhavar SG, Hall AL, O'Brien LT, Gehr-Swain BN, Wilkinson RA, Forrest MS, Dearnaley DP, Ardern-Jones AT, Page EC, Easton DF, Eeles RA; UK Genetic Prostate Cancer Study Collaborators and BAUSSection of Oncology. Prostate cancer in BRCA2 germline mutation carriers isassociated with poorer prognosis. Br J Cancer. 2010 Sep 7;103(6):918-24.
9. Steurer S, Mayer P, Adam M, et al. TMPRSS2-ERG fusions are strongly linked to young patient age in low-grade prostate cancer. Eur Urol 2014;66:978–81.
10. Boutros PC, Fraser M, Harding NJ, et al. Spatial genomic heterogeneity within localized, multifocal prostate cancer. Nat Genet. 2015 May25. doi: 10.1038/ng.3315.
Written by:
Hussein S, Satturwar S, Van der Kwast T.
Department of Laboratory Medicine, Kuwait Cancer Control Center, Kuwait, Kuwait; Department of Pathology, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada.
Abstract: Young-age prostate cancer