ABSTRACT
OBJECTIVE: To investigate whether a diagnosis of precancer poor bone mineral density (PBMD) is associated with higher risk of urological cancer bone metastasis. METHODS: The PearlDiver Database was utilized to conduct a retrospective, propensity-matched cohort analysis of adult patients diagnosed with kidney, bladder, prostate, and testicular cancer with and without a prior diagnosis of PBMD, defined as osteopenia or osteoporosis. Unadjusted and adjusted odds ratios (OR) and 95% confidence intervals are used to compare the rate of newly diagnosed bone metastases between 6months and 3years of the initial cancer diagnosis between the experimental and control cohorts. RESULTS: Among 685,066 patients with urological cancers, precancer PBMD was associated with increased odds of bone metastasis at various time periods (1week, 6months, 1, 2, and 3years). The strongest association was appreciated within 1week of cancer diagnosis (kidney: adjusted odds ratio [aOR], 2.37, P <.001; bladder: [aOR], 2.37, P <.001; prostate: [aOR], 2.84, P <.001; testicular: [aOR], 4.45, P <.001). Bisphosphonates were associated with reduced risk of kidney ([aOR], 0.46, P <.001), bladder ([aOR], 0.61, P <.001), and prostate ([aOR], 0.66, P <.001) cancer bone metastasis. CONCLUSION: Our findings suggest urology patients with PBMD may be predisposed to forming bone metastases as well as presenting with metastatic disease at time of cancer diagnosis. As such, further studies are needed to elucidate whether PBMD plays a role in bone tropism and whether bone health pertains to prolonging bone-free metastasis.
ABSTRACT
BACKGROUND: Poly ADP-ribose polymerase inhibitors (PARPis) are an important class of therapeutics for metastatic castration-resistant prostate cancer (mCRPC). Unlike hormone-based treatments for mCRPC, PARPis are not without drug-related hematological adverse events. OBJECTIVE: To review the evidence on hematological toxicities, including anemia, thrombocytopenia, and neutropenia from PARPis in prostate cancer. STUDY METHODOLOGY: A systematic review and meta-analysis using the PRISMA guidelines was performed for phase II and III randomized controlled trials (RCTs) of PARPis in prostate cancer. PubMed, Embase, and Ovid All EBM reviews-Cochrane were queried from inception to 9 June 2023. The Mantel-Haenszel method was used to report risk ratios (RR) and 95% confidence intervals (CI) for all-grade and high-grade anemia, thrombocytopenia, and neutropenia toxicities. RESULTS: The systematic review retrieved eight phase II and III RCTs; specifically, eight were included in the anemia, five in the all-grade thrombocytopenia and neutropenia, and four in the high-grade thrombocytopenia and neutropenia outcomes. Compared to a placebo and/or other non-PARPi treatments, PARPi use was associated with an increased risk of all-grade anemia (RR, 3.37; 95% CI, 2.37-4.79; p < 0.00001), thrombocytopenia (RR, 4.54; 95% CI, 1.97-10.44; p = 0.0004), and neutropenia (RR, 3.11; 95% CI, 1.60-6.03; p = 0.0008). High-grade anemia (RR, 6.94; 95% CI, 4.06-11.86; p < 0.00001) and thrombocytopenia (RR, 5.52; 95% CI, 2.80-10.88; p < 0.00001) were also associated with an increased risk, while high-grade neutropenia (RR, 3.63; 95% CI, 0.77-17.23; p = 0.10) showed no significant association. Subgroup stratification analyses showed differences in various all-grade and high-grade toxicities. CONCLUSION: PARPis were associated with an increased risk of hematological AEs. Future studies with more pooled RCTs will enhance this understanding and continue to inform patient-physician shared decision-making. Future studies may also have a role in improving the current management strategies for these AEs.
ABSTRACT
Prostate cancer is a global health concern, which has a low survival rate in its advanced stages. Even though second-generation androgen receptor-axis inhibitors serve as the mainstay treatment options, utmost of the metastatic cases progress into castration-resistant prostate cancer after their initial treatment response with poor prognostic outcomes. Hence, there is a dire need to develop effective inhibitors that aim the causal oncogenes tangled in the prostate cancer initiation and progression. Molecular-targeted therapy against E-26 transformation-specific (ETS) transcription factors, particularly ETS-related gene, has gained wide attention as a potential treatment strategy. ETS rearrangements with the male hormone responsive transmembrane protease serine 2 promoter defines a significant number of prostate cancer cases and is responsible for cancer initiation and progression. Notably, inhibition of ETS activity has shown to reduce tumorigenesis, thus highlighting its potential as a clinical therapeutic target. In this review, we recapitulate the various targeted drug approaches, including small molecules, peptidomimetics, nucleic acids, and many others, aimed to suppress ETS activity. Several inhibitors have demonstrated ERG antagonist activity in prostate cancer, but further investigations into their molecular mechanisms and impacts on nontumor ETS-containing tissues is warranted.
