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Consequences of aging are gaining clinical relevance. In transplantation, aging and immunosenescence impact treatment and outcomes. The impact of aging, however, will critically depend on distinguishing healthy, chronological aging from biological aging that may result into frailty. Approximately 15% of individuals older than 65 years are frail, and it is expected that this condition will gain more clinical relevance with an expected increase to greater than 20% over the next 5 years. Clearly, frailty impacts various general aspects of health care and organ transplantation in particular including patient selection, waitlist management and treatment after transplantation. In general, frailty has been characterized by a compromised physiological reserve and an augmented vulnerability. In comparison to healthy aging, inflammatory markers and cytokines are increased in frail older adults. Thus, modifications of the immune response, in addition to physical limitations and changes of metabolism, are likely to impact outcomes after transplantation. Here, we provide a risk assessment of frailty at the time of transplant evaluation and review effects on outcomes and recovery after transplantation. Moreover, we summarize our current understanding of the pathophysiology of frailty and consequences on immune responses and metabolism.

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Objectives To evaluate the oncological and functional outcomes of salvage cryosurgery (SCS) for radiorecurrent prostate cancer (rrPCa). Patients and Methods A total of 169 consecutive patients with biopsy confirmed rrPCa were retrospectively analysed. All patients underwent SCS in a single referral centre between 2006 and 2018. The primary outcome was biochemical recurrence‐free survival (BRFS) according to the Phoenix definition (prostate‐specific antigen [PSA] nadir +2 ng/mL). The secondary outcomes were overall survival, BRFS defined as a PSA level of >0.5 ng/mL, metastasis‐free survival, androgen‐deprivation therapy (ADT)‐free survival, and functional outcomes. Complications were classified according to the Clavien–Dindo system. PSA was measured every 3–6 months postoperatively. Functional outcomes were scored as reported by patients at outpatient visits. Kaplan–Meier survival analysis and uni‐ and multivariable Cox regression were performed. Results The median (interquartile range) follow‐up was 36 (18–66) months. The BRFS after 5 and 8 years was 52% (95% confidence interval [CI] 43–62%) and 45% (95% CI 35–57%), respectively. At multivariable analysis PSA level at initial diagnosis, initial treatment, interval between primary treatment and SCS, age at SCS, and post‐SCS PSA nadir were significant factors for BRFS. The 5‐year ADT‐free survival was 70% (95% CI 62–79%). Clavien–Dindo Grade ≥III complications occurred in 1.2% (two/169) of patients. In all, 19% (29/156) of patients had new‐onset urinary incontinence defined as >1 pad/24 h and 92% (57/62) of patients had new‐onset erectile dysfunction. Persistent urinary fistula occurred in 6.5% (11/169) of patients. Conclusions The present study shows acceptable oncological outcomes of SCS considering the salvage character of the treatment. The occurrence of serious complications such as urinary incontinence and fistula should not be underestimated.

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Objectives To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow‐up in patients with negative systematic biopsy (SB) followed by non‐suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. Patients and Methods A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate‐specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging‐Reporting and Data System (PI‐RADS) ≤2 on mpMRI entered biochemical follow‐up. Follow‐up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow‐up compared to the expected number in the general population (standardized incidence ratio [SIR]). Results In total, 431 patients had non‐suspicious mpMRI and entered biochemical follow‐up. After a median (interquartile range) follow‐up of 41 (23–57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3–7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI‐RADS ≥3) were significant predictive factors for csPCa. Conclusion After negative prior biopsy and non‐suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image‐guided risk‐adapted diagnostic surveillance strategies is warranted.

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