Cost-Effectiveness Analysis of Stockholm 3 Testing Compared to PSA as the Primary Blood Test in the Prostate Cancer Diagnostic Pathway:A Decision Tree Approach

OBJECTIVE: This study evaluated the cost effectiveness of using Stockholm 3 (STHLM3) testing compared to the prostate-specific antigen (PSA) test in the diagnostic pathway for prostate cancer. METHODS: We created a decision tree model for PSA (current standard) and STHLM3 (new alternative). Cost effectiveness was evaluated in a hypothetical cohort of male individuals aged 50–69 years. The study applied a Danish hospital perspective with a time frame restricted to the prostate cancer diagnostic pathway, beginning with the initial PSA/STHLM3 test, and ending with biopsy and histopathological diagnosis. Estimated values from the decision-analytical model were used to calculate the incremental cost-effectiveness ratio. Deterministic and probabilistic sensitivity analyses were conducted to test the robustness of the base-case analysis. RESULTS: The model-based analysis revealed that STHLM3 testing was more effective than the PSA, but also more costly, with an incremental cost-effectiveness ratio of €511.7 (95% credible interval, 359.9–674.3) for each additional correctly classified individual. In the deterministic sensitivity analysis, variations in the cost of STHLM3 had the greatest influence on the incremental cost-effectiveness ratio. In the probabilistic sensitivity analysis, all iterations were positioned in the north-east quadrant of the incremental cost-effectiveness scatterplot. At a willingness to pay of €700 for an additional correctly classified individual, STHLM3 had a 100% probability of being cost effective. CONCLUSIONS: Compared to the PSA test as the initial testing modality in the prostate cancer diagnostic workup, STHLM3 testing showed improved incremental effectiveness, however, at additional costs. The results were sensitive to the cost of the STHLM3 test; therefore, a lower cost of the STHLM3 test would improve its cost effectiveness compared with PSA tests. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40258-022-00741-0

Molecular differences of adipose-derived mesenchymal stem cells between non-responders and responders in treatment of transphincteric perianal fistulas

Background: Injection of autologous adipose tissue (AT) has recently been demonstrated to be an efective and safe treatment for anal fstulas. AT mesenchymal stem cells (AT-MSCs) mediate the healing process, but the relationship between molecular characteristics of AT-MSCs of the injected AT and fstula healing has not been adequately studied. Thus we aimed to characterize the molecular and functional properties of AT-MSCs isolated from autologous AT injected as a treatment of cryptogenic high transsphincteric perianal fstulas and correlate these fndings to the healing process. Methods: 27 patients (age 45±2 years) diagnosed with perianal fstula were enrolled in the study and treated with autologous AT injected around the anal fstula tract. AT-MSCs were isolated for cellular and molecular analyses. The fstula healing was evaluated by MRI scanning after 6 months of treatment. AT-MSC phenotype was compared between responders and non-responders with respect to fstula healing. Results: 52% of all patients exhibited clinical healing of the fstulas as evaluated 6 months after last injection. Cultured AT-MSCs in the responder group had a lower short-term proliferation rate and higher osteoblast diferentiation potential compared to non-responder AT-MSCs. On the other hand, adipocyte diferentiation potential of AT-MSCs was higher in non-responder group. Interestingly, AT-MSCs of responders exhibited lower expression of infammatory and senescence associated genes such as IL1B, NFKB, CDKN2A, TPB3,TGFB1. Conclusion: Our data suggest that cellular quality of the injected AT-MSCs including cell proliferation, diferentiation capacity and secretion of proinfammatory molecules may provide a possible mechanism underlying fstula healing. Furthermore, these biomarkers may be useful to predict a positive fstula healing outcome

Potential synergy between PSMA uptake and tumour blood flow for prediction of human prostate cancer aggressiveness

Background Both prostate-specific membrane antigen (PSMA) uptake and tumour blood flow (TBF) correlate with International Society of Urological Pathology (ISUP) Grade Group (GG) and hence prostate cancer (PCa) aggressiveness. The aim of the present study was to evaluate the potential synergistic benefit of combining the two physiologic parameters for separating significant PCa from insignificant findings. Methods From previous studies of [Rb-82]Rb positron emission tomography (PET) TBF in PCa, the 43 patients that underwent clinical [Ga-68]Ga-PSMA-11 PET were selected for this retrospective study. Tumours were delineated on [Ga-68]Ga-PSMA-11 PET or magnetic resonance imaging. ISUP GG was recorded from 52 lesions. Results [Ga-68]Ga-PSMA-11 maximum standardized uptake value (SUVmax) and [Rb-82]Rb SUVmax correlated moderately with ISUP GG (rho = 0.59 and rho = 0.56, both p < 0.001) and with each other (r = 0.65, p < 0.001). A combined model of [Ga-68]Ga-PSMA-11 and [Rb-82]Rb SUVmax separated ISUP GG > 2 from ISUP GG 1-2 and benign with an area-under-the-curve of 0.85, 96% sensitivity, 74% specificity, and 95% negative predictive value. The combined model performed significantly better than either tracer alone did (p < 0.001), primarily by reducing false negatives from five or six to one (p <= 0.025). Conclusion PSMA uptake and TBF provide complementary information about tumour aggressiveness. We suggest that a combined analysis of PSMA uptake and TBF could significantly improve the negative predictive value and allow non-invasive separation of significant from insignificant PCa