Using Competing Risk of Mortality to Inform the Transition from Prostate Cancer Active Surveillance to Watchful Waiting.

BACKGROUND: For men on active surveillance (AS) for prostate cancer (PCa), disease progression and age-related changes in health may influence decisions about pursuing curative treatment. OBJECTIVE: To evaluate the predicted PCa and non-PCa mortality at the time of reclassification among men on AS, to identify clinical criteria for considering a transition from AS to watchful waiting (WW). DESIGN, SETTING, AND PARTICIPANTS: Patients enrolled in a large AS program who experienced biopsy grade reclassification (Gleason grade increase) were retrospectively examined. All patients who had complete documentation of medical comorbidities at reclassification were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A validated model was used to assess 10- and 15-yr untreated PCa and non-PCa mortalities based on patient comorbidities and PCa clinical characteristics. We compared the ratio of predicted PCa mortality with predicted non-PCa mortality ("predicted mortality ratio") and divided patients into four risk tiers based on this ratio: (1) tier 1 (ratio: >0.33), (2) tier 2 (ratio 0.33-0.20), (3) tier 3 (ratio 0.20-0.10), and (4) tier 4 (ratio <0.10). RESULTS AND LIMITATIONS: Of the 344 men who were reclassified, 98 (28%) were in risk tier 1, 85 (25%) in tier 2, 93 (27%) in tier 3, and 68 (20%) in tier 4 for 10-yr mortality. Fifteen-year risk tiers were distributed similarly. The 23 (6.7%) men who met the "transition triad" (age >75 yr, Charlson Comorbidity Index >3, and grade group ≤2) had a 14-fold higher non-PCa mortality risk and a lower predicted mortality ratio than those who did not (0.07 vs 0.23, p < 0.001). The primary limitations of our study included its retrospective nature and the use of predicted mortalities. CONCLUSIONS: At reclassification, nearly half of patients had a more than five-fold and one in five patients had a more than ten-fold higher risk of non-PCa death than patients having a risk of untreated PCa death. Despite a more significant cancer diagnosis, a transition to WW for older men with multiple comorbidities and grade group <3 PCa should be considered. PATIENT SUMMARY: Men with favorable-risk prostate cancer and life expectancy of >10 yr are often enrolled in active surveillance, which entails delay of curative treatment until there is evidence of more aggressive disease. We examined a group of men on active surveillance who developed more aggressive disease, and found, nevertheless, that the majority of these men continued to have a dramatically higher risk of death from non-prostate cancer causes than from prostate cancer based on a risk prediction tool. For men older than 75 yr, who have multiple medical conditions and who do not have higher-grade cancer, it may be reasonable to reconsider the need for curative treatment given the low risk of death from prostate cancer compared with the risk of death from other causes.

New frontiers in fertility preservation: a hypothesis on fertility optimization in men with hypergonadotrophic hypogonadism.

Strategies exist that can mitigate the risk of causing iatrogenic infertility when men require testosterone replacement therapy (TRT). This article reviews the current medical therapies that preserve spermatogenesis when TRT is indicated. Furthermore, we highlight the re-emerging concept of hypothalamic-pituitary-gonadal (HPG) axis reset in hypergonadotrophic, hypogonadal infertile men who are planning sperm retrieval procedures. Finally, we present our hypothesis for a novel protocol to optimize hypergonadotrophic hypogonadal men before sperm extraction surgeries hormonally.

A Prospective Study of the Urinary and Gastrointestinal Microbiome in Prepubertal Males.

OBJECTIVE: To determine if urinary microbial communities similar to those described in adults exist in children and to profile the urinary and gastrointestinal microbiome in children presenting to urology for both routine and complex urologic procedures. METHODS: Prepubertal boys (n = 20, ages 3 months-8 years; median age 15 months) who required elective urologic procedures were eligible. Urine samples were collected via sterile catheterization and fecal samples were obtained by rectal swabs. DNA was extracted from urine pellet and fecal samples and subjected to bacterial profiling via 16S rDNA Illumina sequencing and 16S rDNA quantitative polymerase chain reaction. We assessed within and between sample diversity and differential species abundance between samples. RESULTS: Urine samples had low bacterial biomass that reflected the presence of bacterial populations. The most abundant genera detected in urine samples are not common to skin microbiota and several of the genera have been previously identified in the urinary microbiome of adults. We report presumably atypical compositional differences in both the urinary and gastrointestinal microbiome in children with prior antibiotic exposure and highlight an important case of a child who had undergone lifelong antibiotic treatment as prophylaxis for congenital abnormalities. CONCLUSION: This study provides one of the first characterizations of the urinary microbiome in prepubertal males. Defining the baseline healthy microbiome in children may lay the foundation for understanding the long-term impact of factors such as antibiotic use in the development of a healthy microbiome as well as the development of future urologic and gastrointestinal diseases.