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Given the demographic trends toward a considerably longer life expectancy, the percentage of elderly patients with prostate cancer will increase further in the upcoming decades. Therefore, the question arises, should patients ≥75 years old be offered radical prostatectomy and under which circumstances? For treatment decision-making, life expectancy is more important than biological age. As a result, a patient's health and mental status has to be determined and radical treatment should only be offered to those who are fit. As perioperative morbidity and mortality in these patients is increased relative to younger patients, patient selection according to comorbidities is a key issue that needs to be addressed. It is known from the literature that elderly men show notably worse tumor characteristics, leading to worse oncologic outcomes after treatment. Moreover, elderly patients also demonstrate worse postoperative recovery of continence and erectile function. As the absolute rates of both oncological and functional outcomes are still very reasonable in patients ≥75 years, a radical prostatectomy can be offered to highly selected and healthy elderly patients. Nevertheless, patients clearly need to be informed about the worse outcomes and higher perioperative risks compared to younger patients.

Simple Summary: The prognostic value of lymphovascular or perineural invasion in prostate cancer specimens regarding oncological outcomes after radical prostatectomy is unclear. Within a contemporary study cohort of 822 prostate cancer patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In univariable Cox regression models, lymphovascular invasion and perineural invasion were both associated with higher rates of biochemical recurrence (BCR). However, after multivariable adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion was not found to be an independent predictor for BCR. These phenomes may be explained by the strong association between the Gleason Grade Group and pathologic tumor stage with lymphovascular as well as perineural invasion. Objective: The aim of this study was to test for the association between lymphovascular invasion or perineural invasion in radical prostatectomy (RP) specimens and biochemical recurrence (BCR). Methods: Relying on a tertiary-care database, we identified prostate cancer patients treated with RP between January 2014 and June 2023. Of these, the majority underwent robotic-assisted RP (81%). Kaplan–Meier survival analyses and Cox regression models addressed BCR according to either lymphovascular invasion or perineural invasion in RP specimens. Additionally, the linear trend test assessed the association between the Gleason Grade Group or pathologic tumor stage and lymphovascular or perineural invasion. Results: Of 822 patients, 78 (9%) exhibited lymphovascular invasion and 633 (77%) exhibited perineural invasion in RP specimens. In survival analyses, the five-year BCR-free survival rates were 62% in patients with lymphovascular invasion vs. 70% in patients without lymphovascular invasion (p = 0.04) and 64% in patients with perineural invasion vs. 82% in patients without perineural invasion (p = 0.01). In univariable Cox regression models, lymphovascular invasion (hazard ratio 1.58, 95% confidence interval 1.01–2.47; p = 0.045) and perineural invasion (hazard ratio 1.77, 95% confidence interval 1.13–2.77; p = 0.013) were both associated with a higher BCR rate. After accounting for age at surgery, PSA value, pathologic tumor stage, Gleason Grade Group, lymph node invasion, positive surgical margin, surgical approach, and adjuvant radiation therapy, lymphovascular (p = 0.740) or perineural invasion (p = 0.341) were not significantly associated with a higher BCR since the Gleason Grade Group and pathologic tumor stage highly correlated with lymphovascular as well as perineural invasion. Conclusions: In univariable models, lymphovascular or perineural invasion is associated with BCR. After adjustment for standard pathologic tumor characteristics, lymphovascular or perineural invasion is not an independent predictor for BCR. [ABSTRACT FROM AUTHOR]

Simple Summary: The current real-world study suggests that important differences exist in patients progressing to mCRPC. Specifically, we found that a proportion of over 20% of patients progress without a PSA level rise, emphasizing the importance of regular staging intervals. Moreover, we found that patients with worse PSA responses are at higher risk for biochemical progression, emphasizing the need for regular PSA check-ups and kinetic measurements. However, no differences in PFS and OS outcomes between these patients were observed. Finally, staging with PSMA-PET/CT might provide better PFS and OS, relative to conventionally staged mCRPC patients. However, this observation may be substantially influenced by the detection of earlier disease progression and the possibility of treatment in patients with a lower metastatic burden, as well as more contemporary patients with better treatment options. Background/Objectives: Progression to metastatic castration-resistant prostate cancer (mCRPC) is defined either biochemically, radiographically or both. Moreover, staging for mCRPC can be performed either conventionally or with molecular imaging such as prostate-specific membrane antigen computer tomography (PSMA-PET/CT). Methods: We relied on the Frankfurt Metastatic Cancer Database of the Prostate (FRAMCAP) database to compare progression-free (PFS) and overall survival (OS) outcomes regarding the cause of castration resistance and the staging modality used. Results: Overall, 35% progressed to mCRPC biochemically vs. 23% radiographically vs. 42% biochemically + radiographically. The PSA nadir in mHSPC (1.4 vs. 0.4 vs. 0.8 ng/mL) and PSA level at mCRPC progression (15 vs. 2 vs. 21 ng/mL, both p ≤ 0.01) were significantly higher for biochemical vs. radiographic vs. both progressed patients. In PFS and OS analyses, no significant differences were observed among all three compared groups. In the comparison of the staging used for progression to mCRPC, 67% received conventional vs. 33% PSMA-PET/CT, with higher metastatic burden in mHSPC and osseous lesions in mCRPC for conventionally staged patients (both p < 0.01). In PFS (15.3 vs. 10.1 months, hazard ratio [HR]: 0.75) and OS analyses (52.6 vs. 34.3 months, HR: 0.61, both p < 0.05), PSMA-PET/CT harbored better prognosis; however, this did not hold after multivariable adjustment. Similar results were observed for further analyses in second- and third-line mCRPC or patients with a PSA level of ≥2 ng/mL. Conclusions: The cause of progression to mCRPC seems not to influence cancer-control outcomes, despite important baseline tumor characteristic differences. The PSMA-PET/CT staging modality might be associated with better PFS and OS outcomes, possibly due to its more sensitive detection of progression or new metastatic lesions. [ABSTRACT FROM AUTHOR]

Background: Biochemical recurrence (BCR) represents the rise of prostate-specific antigen (PSA) levels after treatment with curative radical prostatectomy (RP) or radiation for prostate cancer. The objective of the current study was to test for the association between patient characteristics, namely age, body mass index (BMI), as well as prostate volume at surgery, and BCR after RP. Material and Methods: Within a tertiary care database, patients with prostate cancer treated with RP between January 2014 and June 2023 were included. Kaplan–Meier survival analyses and Cox regression models addressed BCR after RP according to patient characteristics. Results: Of 821 patients, the median age was 66 years (interquartile range [IQR] 61–71 years), BMI was 26.2 kg/m2 (IQR 24.3–28.8 kg/m2), and prostate volume was 40 cm3 (IQR 30–55 cm3). Median follow-up was 20 months. In survival analyses, the three-year BCR-free survival rates were 81 vs. 84 vs. 81% in patients aged ≤60 vs. 61–69 vs. 70 years (p = 0.1). In patients with BMI < 25.0 vs. 25.0–29.9 vs. ≥30.0 kg/m2, the three-year BCR-free survival rates were 84 vs. 81 vs. 84% (p = 0.7). In patients with prostate volume ≤40 vs. >40 cm3, the three-year BCR-free survival rates were 85 vs. 80% (p = 0.004). In multivariable Cox regression models accounting for patient and pathologic tumor characteristics and adjuvant radiation therapy, a higher prostate volume independently predicted BCR as continuous (hazard ratio 1.012, 95% confidence interval 1.005–1.019; p < 0.001), as well as categorized the variable based on the median (hazard ratio 1.66, 95% confidence interval 1.17–2.36; p = 0.005). Conversely, neither age nor BMI were significantly associated with BCR after RP. Conclusions: The higher prostate volume independently predicted BCR after RP, but not age or BMI at surgery. Consequently, patients with an elevated prostate volume should be considered for closer postoperative follow-up. [ABSTRACT FROM AUTHOR]

Simple Summary: Radioligand therapy (RLT) usually consists of predefined cycles of 177Lu-PSMA-617 every 6–8 weeks. Although side-effects of RLT are considered well tolerable, cumulative absorbed doses in kidneys and an increased probability of chronic renal failure in responders remain concerns. The aim of our retrospective study, therefore, was to assess the efficacy and safety of intermittent, response-adapted RLT with 177Lu-PSMA-617 in oligometastatic mCRPC patients. Intermittent RLT with 177Lu-PSMA-617 is effective and can result in long-lasting disease control in selected patients even when including multiple treatment-free periods. 177Lu-PSMA-617 radioligand therapy (177Lu-PSMA-RLT) in patients with metastatic castration-resistant prostate cancer (mCRPC) currently consists of 4–6 cycles of 6.0–7.4 GBq of 177Lu-PSMA-617 each every 6–8 weeks. While safety and efficacy could be demonstrated in larger prospective trials irrespective of the tumor burden at 177Lu-PSMA RLT initiation, increased renal absorbed doses due to a reduced tumor sink effect in early responding, oligometastatic mCRPC patients pose difficulties. Response-adapted, dose distributing, intermittent treatment with up to six cycles has not been routinely performed, due to concerns about the potential loss of disease control. Treatment was discontinued in 19 early-responding patients with oligometastatic tumor burden after two (IQR 2–3) cycles of 177Lu-PSMA-RLT and 6.5 ± 0.7 GBq per cycle and resumed upon 68Ga-PSMA-11-PET/CT-based progression (according to the PCWG3 criteria). Subsequent treatment breaks were imposed if a PSMA-based imaging response could be achieved. A total of five (IQR 3–6) cycles reaching a cumulative activity of 32 ± 11 GBq were applied. A routine blood work-up including blood counts and liver and renal function was measured throughout the 177Lu-PSMA-RLT and follow-up to grade toxicity according to CTCAE v5.0 criteria. Survival outcome was calculated based on the Kaplan–Meier method. In total, treatment-free periods of 9 (IQR 6–17) cumulative months and the application of 177Lu-PSMA-RLT cycles over 16 (IQR 9–22) months could be achieved. Fifteen (84%) patients responded to subsequent cycles after the first treatment break and in 7/19 (37%) patients, intermittent 177Lu-PSMA-RLT consisted of ≥2 treatment breaks. The median PFS was 27 months (95% CI: 23–31) and overall survival was 45 months (95% CI: 28–62). No grade ≥3 hematological or renal toxicities could be observed during the 45 ± 21 months of follow-up. The cumulative mean renal absorbed dose was 16.7 ± 8.3 Gy and 0.53 ± 0.21 Gy/GBq. Intermittent radioligand therapy with 177Lu-PSMA-617 is feasible in early-responding patients with oligometastatic disease. A late onset of progression after subsequent cycles and the absence of significant toxicity warrants further investigation of the concept of intermittent treatment in selected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The transmembrane protein prostate-specific membrane antigen (PSMA) has emerged as a target for both molecular imaging and PSMA-directed radioligand therapy (RLT). Normal organs, including the liver and salivary glands, exhibit physiological PSMA-ligand accumulation and have, therefore, gained interest as decisive landmarks for the semiquantitative classification of tumoral uptake on [68Ga]Ga-PSMA-11 PET/CT imaging. The presented study aims to assess the change in uptake to reference organs, including the liver, parotid and salivary glands after radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 in relation to pretreatment imaging metrics. This study aims to assess the change in uptake to reference organs, including the liver, parotid and salivary glands after radioligand therapy (RLT) with [177Lu]Lu-PSMA-617 in relation to pretreatment imaging metrics. Eighty-five patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging prior to (pre RLT PET) and after (post RLT PET) a median of 3 (IQR 2-6) RLT cycles with [177Lu]Lu-PSMA-617. PSMA-positive tumor burden was stratified into 4 groups based on modified PROMISE criteria (oligofocal, multifocal, disseminated, diffuse). Uptake (SUVmean, SUVmax) in liver tissue, parotid and submandibular glands was measured. A control group was established with 54 patients who had received two separate PET acquisitions following the same protocol (PET1, PET2) within 12 months for localized or oligofocal prostate cancer without RLT in the interim. Baseline uptake values (SUVmean, SUVmax) in parotid (10.8 ± 3.2, 16.8 ± 5.4) and submandibular glands (11.3 ± 2.8, 18.1 ± 4.7) are 2-fold compared to liver uptake (4.9 ± 1.4, 7.7 ± 2.0), with no significant change between PET 1 and PET 2 in the control group. In the RLT group, increasing tumor burden class is significantly associated with decreasing uptake in the liver (p = 0.013), parotid (p < 0.001) and submandibular glands (p < 0.001); this tumor sink effect by respective tumor burden is widely maintained after RLT (p = 0.011, p < 0.001, p < 0.001). RLT has a significant impact on salivary gland uptake with decreasing values per patient in all groups of disease burden change (up to −30.4% in submandibular glands, p < 0.001), while liver tissue shows rising values in patients with declining tumor burden throughout RLT (+18.6%, p = 0.020). Uptake in liver tissue and salivary glands on [68Ga]Ga-PSMA-11 PET/CT imaging is inversely related to tumor burden prior to and following RLT with [177Lu]Lu-PSMA-617. Per patient, salivary gland uptake is further reduced throughout RLT independently from tumor burden, while changes in liver uptake remain burden-dependent. Liver and salivary gland uptake-derived metrics and segmentation thresholds may thus be of limited value when used as reference for response assessment to RLT. [ABSTRACT FROM AUTHOR]

The contribution of this paper is twofold. First, we examine the impact of class size on student evaluations of instructor performance using a sample of approximately 1400 economics classes held at the University of Munich from Fall 1998 to Summer 2007. We offer confirmatory evidence for the recent finding of a large, highly significant, and nonlinear negative impact of class size on student evaluations of instructor effectiveness that is robust to the inclusion of course and instructor fixed effects. Beyond that, we run a survey based on the contingent valuation method and a representative sample of all Munich students of management science to quantify the welfare surplus of preferred class size. We find the average monetary value students ascribe to their preferred class size to lie between 5 and 300 Euros per semester and student. In an upper bound scenario, implied Hicksian surpluses can reach values of close to 500 Euros per semester and student. (Contains 8 tables and 8 figures.)

Simple Summary: The prostate-specific membrane antigen (PSMA), a transmembrane protein frequently present on prostate cancer cells, has gained considerable interest as a target for both molecular imaging and therapy. Patients with metastatic castration-resistant prostate cancer can be successfully treated by delivery of beta particle-emitting 177Lutetium to the prostate-specific antigen in a therapeutic concept termed radioligand therapy. Imaging with positron emission tomography (PET) plays a crucial role in patient selection prior to radioligand therapy and subsequent molecular response assessment. The presented study aims to investigate the role of quantitative uptake parameters on baseline 68Gallium-PSMA-11 PET/CT imaging as to their association with lesion response to radioligand therapy at individual tumor sites. Special emphasis is placed on the utility of PSMA-uptake thresholds for pretherapeutic prediction of lesion response. Baseline uptake on prostate-specific membrane antigen (PSMA)-targeted imaging is a prerequisite for radioligand therapy (RLT) with [177Lu]Lu-PSMA-617. This study aims to quantify lesion-based response to RLT in relation to pretreatment standard molecular imaging metrics derived from [68Ga]Ga-PSMA-11 PET/CT. Sixty-one patients with mCRPC underwent [68Ga]Ga-PSMA-11 PET/CT imaging before and after a median of 4 (IQR 2–6) RLT cycles. Maximum and mean standardized uptake values (SUVmax, SUVmean), as well as tumor-to-liver ratio (TLR), were assessed. A median of 12 (IQR 7–17) lesions was analyzed per patient, resulting in a total of 718 lesions. Lesions with ≥30% SUVmax decline or falling below the blood pool uptake were considered responsive; ≥30% SUVmax increase marked lesion progression. Additionally, 4-point visual scoring was performed according to E-PSMA consensus. In total, 550/718 (76.6%) lesions responded to RLT, including 389/507 (76.7%) bone metastases and 143/181 (79.0%) lymph node metastases. Baseline SUVmax, SUVmean, and TLR values were associated with lesion response by a moderate but significant correlation (rs = 0.33, p < 0.001, rs = 0.32, p < 0.001, and rs = 0.31, p < 0.001, respectively). For the classification of lesion progression based on baseline PSMA uptake, receiver operating characteristics (ROC) found SUVmax, SUVmean, and TLR to have comparable discriminatory value (AUC 0.85, 0.87, and 0.83). Of 42 tumor sites with baseline uptake below the liver (V-score < 2), 19/42 (45.2%) were responsive, 9/42 (21.4%) were stable, and 14/42 (33.3%) showed progression, leaving liver uptake a threshold with low prognostic value for the identification of RLT-refractory lesions (PPV 33%). This was observed accordingly for various liver uptake-based thresholds, including TLR < 1.5, <2.0 with a PPV at 24%, 20%, respectively. Standard uptake parameters quantified by routine baseline [68Ga]Ga-PSMA-11 PET/CT are moderately associated with post-treatment lesion response to [177Lu]Lu-PSMA-617. Commonly applied liver-based uptake thresholds have limited value in predicting refractory lesions at individual tumor sites. [ABSTRACT FROM AUTHOR]