Life expectancy is rising worldwide with significant clinical and treatment implications. It is most important to ascertain who the treated patient is, in regards to his comorbidity profile, and biological age in addition to his chronological age. It has been shown that comorbidity profile is more important than age in predicting overall mortality in localized PC. Men over the age of 70 should be managed according to their health status and not according to their age. Health status can be defined as fit, frail or disabled/with severe comorbidities. Fit patients are expected to tolerate any form of standard treatment and should receive the same treatment as younger men. Frail men are those that if their problems are corrected, they can be considered fit for standard PC therapies.
PC is more common as men get older with an incidence of 1.5% in men under the age of 50 and 55% in men over 70. PC is also more prevalently diagnosed in developed countries, when compared to developing countries. With increasing age, aggressive PC disease is more prevalent with T3 disease, Gleason score >7, multifocal disease, and tumor volume rising significantly in men older than 70 compared to men younger than 70 – 21.8% vs. 4%, 42.4% vs. 15.4%, 63.9% vs. 45.4%, and 0.4 ml vs. 0.1 ml, respectively. Additionally, in men older than 75, although representing approximately a quarter of all PC cases, they contribute almost half of all M1 cases, resulting in substantially increased mortality as well.
Dr. Briganti continued to talk about age related mechanisms favoring both age associated diseases and cancer. These include senescence, genomic and epigenomic instability manifested through mutation accumulation with DNA damage, free radicals, and oxidative stress. Senescence is a persistent hypo-replicative state with a non-linear rate of senescent cell accumulation throughout the lifespan, but is significantly accelerated with aging. Major regulators of apoptosis and senescence, such as p53 or p16, are tumor suppressors. Their inactivation may result in cancer. Various events causing inflammation and accumulation of aging processes lead eventually to aggressive PC progression.
Dr. Briganti brought the question of screening for PC in the elderly population. This is a controversial topic, especially since the recent US preventative service task force recommendations again PC screening, despite its recent change of the recommendation to screen middle aged men (55-69) from grade D to grade C. However, for men above the age of 70, the recommendation has remained grade D. In contrast, when looking at other major relevant organizations, such as the American Cancer Society (ACS), they clearly state that asymptomatic men with at least a 10-year life expectancy, can have an opportunity to make an informed decision with their health care provider about screening. The American Urological Association (AUA) goes even further and states that men aged 70 or more in excellent health may actually benefit from PC screening.
Finally Dr. Briganti addressed the question of local treatment in the elderly PC patients. 3 major trials demonstrated relevant data. Starting with the SPCG-4 trial (comparing radical prostatectomy [RP] to watchful waiting in early prostate cancer. This trial showed that in men over the age of 65 no significant differences were found between both arms of treatment with regards to PC death, overall mortality (OM) and distant metastasis. The PIVOT trial (comparing RP vs. observation for localized PC) also showed no difference in PC death (p=0.63). The 3rd final and most recent trial was the PROTECT trial (comparing outcomes 10 years after monitoring, RP or radiotherapy for localized) again, showing no difference.
It is also important to take into account the lead time bias and length time bias when diagnosing PC in elderly patients, significantly impacting results, when comparing to the younger patients.
Dr. Briganti concluded his presentation by reiterating that older patients are more likely to present with more advanced and aggressive PC disease compared to younger men, likely due to a combination of diagnostic biases and biological mechanisms. Biological and not chronological age represents the most important factor for clinical decision making. Therefore, life expectancy and comorbidity profile assessments are mandatory before treating elderly patients. The optimal management strategy for these patients requires a delicate balance between risk of under treatment and over treatment.
Presented By: Alberto Briganti, MD, Urological Research Institute, Milan, Italy
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA