Not all men are equal when it comes to prostate cancer and certain populations require a special approach. This is particularly the case for young subjects, as explained by Dr Arthur Peyrottes (Saint-Louis hospital, Paris) during the congress.
Younger subjects more exposed
The question of what constitutes a “young” subject when talking about prostate cancer remains complex. In France, the diagnosis is made at a median age of 69 years. The risk of developing prostate cancer increases with age. “If, among those under 30, the risk is around 5%, it reaches almost 60% after age 79,” underlines Dr Peyrottes. On this basis, “the notion of ‘young age’ remains vague, lying somewhere between 30 and 45-50 years.” By referring to the main studies on screening, such as PLCO or ERPC, it is possible to give a more precise answer. For Dr Peyrottes, these studies suggest that the age of start of screening, often between 45 and 50 years, can be considered as a reference to define what is a “young subject” in the context of prostate cancer.
These patients “have a higher risk of developing aggressive forms of the disease. There is also a higher probability that they have a particular clinical history or underlying predisposing oncogenetic syndrome, which may influence the prognosis,” explains the urologist.
Therefore, “Given their young age, these men require a therapeutic approach balanced between maximum effectiveness and minimal adverse effects.” While awaiting more robust but already promising literature on the oncological effectiveness of focal treatments in this particular population, two standard therapeutic interventions are available: prostatectomy and radiotherapy. In the case of prostatectomy, in the case of aggressive disease in a young patient, the question arises as to whether it is relevant to offer perioperative drug intensification. “C“is a hope among these young men who could be good candidates”, believes Dr Peyrottes. Two trials are underway, including the Proteus study which compares a strategy combining, perioperatively, 1st generation hormone therapy + apalutamide (selective androgen receptor inhibitor) versus 1st generation hormone therapy + placebo. Another trial, French, Sugar, studies the impact of darolutamide before and after surgery.
The weight of family history
Another specific population: men at high risk of prostate cancer (risk greater than 25% over a lifetime). These are those with a family history, Afro-Caribbean ancestry or carriers of germline mutations for genes promoting prostate cancer (ATM, BRCA1, BRCA2, CHEK2, HOXB13, MSH2, PALB2). As Professor Romain Mathieu (urology department, CHU Pontchaillou, Rennes) pointed out, “the men affected are more numerous than we believe: up to 57% of men with prostate cancer have a family history (more than 90% in Guadeloupe) and a significant proportion in Île-de-France are of Afro-Caribbean origin, while 11-12% of patients presenting with metastases at diagnosis and nearly 5% for localized forms carry genetic mutations associated with the disease.. Family history is a determining factor in prostate cancer, with an odds ratio varying from 1.2 to 8.4 depending on the study. The risk increases according to the degree of relationship and the severity of the cancer in men related to the 1is or 2nd degree. In addition, regarding Afro-Caribbean ancestry, the risk of being diagnosed with prostate cancer increases from 13% among men with white skin to 29% among those with black skin. Finally, BRCA2 mutations confer a relative risk of 2.64, compared to 1.35 for BRCA1, 3.25 for HoxB13, 4.4 for ATM or 3.62 for MSH.
The risk of aggressive cancer is also greater in these populations. For example, in the event of a BRCA2 gene mutation, the probability of a Gleason score > 6 is 63% compared to 27% in the general population. And the more significant the family history of prostate cancer, the greater the risk of developing high-grade cancer.
In this context, all learned societies agree that a PSA measurement must be carried out from the age of 40 or 45 in these men: 45 years in the case of family history or Afro-Caribbean ancestry, and 40 years in case of BRCA gene abnormality. The French Association of Urology (AFU) also emphasizes the importance of a rectal exam. “ But the 2024 recommendations from the AFU cancer committee go furtherindicates Romain Mathieu, particularly for patients carrying mutations in the BRCA2 and HOXB13 genes. » In these patients, the committee not only recommends a rectal examination and a PSA measurement from the age of 40 but also suggests that a multiparametric MRI could be considered, independently of the PSA level (low level of evidence). Indeed, “in patients with a family history, almost 50% of CaP were diagnosed despite a normal PSA”. The use of MRI presents a diagnostic benefit in young patients, provided it is read by expert radiologists.
Based on session EA10: Personalized management of populations at high risk of CaP in young patients
