Impact of persistent PSA after salvage radical prostatectomy: a multicenter study.

BACKGROUND AND OBJECTIVE: Persistent prostatic specific antigen (PSA) represents a poor prognostic factor for recurrence after radical prostatectomy (RP). However, the impact of persistent PSA on oncologic outcomes in patients undergoing salvage RP is unknown. To investigate the impact of persistent PSA after salvage RP on long-term oncologic outcomes. MATERIAL AND METHODS: Patients who underwent salvage RP for recurrent prostate cancer between 2000 and 2021 were identified from twelve high-volume centers. Only patients with available PSA after salvage RP were included. Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of persistent PSA on biochemical recurrence (BCR), metastasis and any death after salvage RP. Persistent PSA was defined as a PSA-value ≥ 0.1 ng/ml, at first PSA-measurement after salvage RP. RESULTS: Overall, 580 patients were identified. Of those, 42% (n = 242) harbored persistent PSA. Median follow-up after salvage RP was 38 months, median time to salvage RP was 64 months and median time to first PSA after salvage RP was 2.2 months. At 84 months after salvage RP, BCR-free, metastasis-free, and overall survival was 6.6 vs. 59%, 71 vs. 88% and 77 vs. 94% for patients with persistent vs. undetectable PSA after salvage RP (all p < 0.01). In multivariable Cox models persistent PSA was an independent predictor for BCR (HR: 5.47, p < 0.001) and death (HR: 3.07, p < 0.01). CONCLUSION: Persistent PSA is common after salvage RP and represents an independent predictor for worse oncologic outcomes. Patients undergoing salvage RP should be closely monitored after surgery to identify those with persistent PSA.

Recurrent Gleason Score 6 Prostate Cancer After Radiotherapy or Ablation: Should We Observe Them All? Results from a Large Multicenter Salvage Radical Prostatectomy Consortium.

BACKGROUND: Salvage radical prostatectomy (sRP) yields poor functional outcomes and relatively high complication rates. Gleason score (GS) 6 prostate cancer (PCa) has genetic and clinical features showing little, if not absent, metastatic potential. However, the behavior of GS 6 PCa recurring after previous PCa treatment including radiotherapy and/or ablation has not been investigated. OBJECTIVE: To evaluate the oncological outcomes of sRP for radio- and/or ablation-recurrent GS 6 PCa. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data of sRP for recurrent PCa after local nonsurgical treatment were collected from 14 tertiary referral centers from 2000 to 2021. INTERVENTION: Prostate biopsy before sRP and sRP. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: A survival analysis was performed for pre-sRP biopsy and sRP-proven GS 6. Concordance between PCa at pre-sRP biopsy and sRP histology was assessed. RESULTS AND LIMITATIONS: We included GS 6 recurrent PCa at pre-sRP biopsy (n = 142) and at sRP (n = 50), as two cohorts. The majority had primary radiotherapy and/or brachytherapy (83.8% of GS 6 patients at pre-sRP biopsy; 78% of GS 6 patients at sRP) and whole-gland treatments (91% biopsy; 85.1% sRP). Biopsy GS 6 10-yr metastasis, cancer-specific survival (CSS), and overall survival (OS) were 79% (95% confidence interval [CI] 61-89%), 98% (95-99%), and 89% (78-95%), respectively. Upgrading at sRP was 69%, 35.5% had a pT3 stage, and 13.4% had positive nodes. The sRP GS 6 10-yr metastasis-free survival, CSS, and OS were 100%, 100%, and 90% (95% CI 58-98%) respectively; pT3 and pN1 disease were found in 12% and 0%, respectively. Overall complications, high-grade complications, and severe incontinence were experienced by >50%, >10%, and >15% of men, respectively (in both the biopsy and the sRP cohorts). Limitations include the retrospective nature of the study and absence of a centralized pathological review. CONCLUSIONS: GS 6 sRP-proven PCa recurring after nonsurgical primary treatment has almost no metastatic potential, while patients experience relevant morbidity of the procedure. However, a significant proportion of GS 6 cases at pre-sRP biopsy are upgraded at sRP. In the idea not to overtreat, efforts should be made to improve the diagnostic accuracy of pre-sRP biopsy. PATIENT SUMMARY: We investigated the oncological results of salvage radical prostatectomy for recurrent prostate cancer of Gleason score (GS) 6 category. We found a very low malignant potential of GS 6 confirmed at salvage radical prostatectomy despite surgical complications being relatively high. Nonetheless, biopsy GS 6 was frequently upgraded and had less optimal oncological control. Overtreatment for recurrent GS 6 after nonsurgical first-line treatment should be avoided, and efforts should be made to increase the diagnostic accuracy of biopsies for recurrent disease.

Oncologic Outcomes of Lymph Node Dissection at Salvage Radical Prostatectomy.

BACKGROUND: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. OBJECTIVE: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. PATIENTS AND METHODS: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan-Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). RESULTS: Of 853 SRP patients, 87% (n = 727) underwent LND, and 21% (n = 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p < 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p < 0.001), and CSS rates were 94% vs. 96% vs. 82% (p = 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77, p < 0.001) and death (HR: 2.89, p < 0.001). CONCLUSIONS: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.

Effects of Specialist Palliative Care for Patients Undergoing Major Abdominal Surgery for Cancer: A Randomized Clinical Trial.

Importance: Specialist palliative care benefits patients undergoing medical treatment of cancer; however, data are lacking on whether patients undergoing surgery for cancer similarly benefit from specialist palliative care. Objective: To determine the effect of a specialist palliative care intervention on patients undergoing surgery for cure or durable control of cancer. Design, Setting, and Participants: This was a single-center randomized clinical trial conducted from March 1, 2018, to October 28, 2021. Patients scheduled for specified intra-abdominal cancer operations were recruited from an academic urban referral center in the Southeastern US. Intervention: Preoperative consultation with palliative care specialists and postoperative inpatient and outpatient palliative care follow-up for 90 days. Main Outcomes and Measures: The prespecified primary end point was physical and functional quality of life (QoL) at postoperative day (POD) 90, measured by the Functional Assessment of Cancer Therapy-General (FACT-G) Trial Outcome Index (TOI), which is scored on a range of 0 to 56 with higher scores representing higher physical and functional QoL. Prespecified secondary end points included overall QoL at POD 90 measured by FACT-G, days alive at home until POD 90, and 1-year overall survival. Multivariable proportional odds logistic regression and Cox proportional hazards regression models were used to test the hypothesis that the intervention improved each of these end points relative to usual care in an intention-to-treat analysis. Results: A total of 235 eligible patients (median [IQR] age, 65.0 [56.8-71.1] years; 141 male [60.0%]) were randomly assigned to the intervention or usual care group in a 1:1 ratio. Specialist palliative care was received by 114 patients (97%) in the intervention group and 1 patient (1%) in the usual care group. Adjusted median scores on the FACT-G TOI measure of physical and functional QoL did not differ between groups (intervention score, 46.77; 95% CI, 44.18-49.04; usual care score, 46.23; 95% CI, 43.08-48.14; P = .46). Intervention vs usual care group odds ratio (OR) was 1.17 (95% CI, 0.77-1.80). Palliative care did not improve overall QoL measured by the FACT-G score (intervention vs usual care OR, 1.09; 95% CI, 0.75-1.58), days alive at home (OR, 0.87; 95% CI, 0.69-1.11), or 1-year overall survival (hazard ratio, 0.97; 95% CI, 0.50-1.88). Conclusions and Relevance: This randomized clinical trial showed no evidence that early specialist palliative care improves the QoL of patients undergoing nonpalliative cancer operations. Trial Registration: ClinicalTrials.gov Identifier: NCT03436290.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer Following First-line Nonsurgical Treatment: Validation of the European Association of Urology Criteria in a Large, Multicenter, Contemporary Cohort.

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000-2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen-free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13-2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. PATIENT SUMMARY: We looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria.

Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.

Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1+ASPN+FAP+ENG+) along with fewer T cells, elevated T cell dysfunction, and increased C1QB+TREM2+APOE+-M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.

Prospective Multicenter Comparison of Open and Robotic Radical Prostatectomy: The PROST-QA/RP2 Consortium.

PURPOSE: Our goal was to evaluate the comparative effectiveness of robot-assisted laparoscopic prostatectomy (RALP) and open radical prostatectomy (ORP) in a multicenter study. MATERIALS AND METHODS: We evaluated men with localized prostate cancer at 11 high-volume academic medical centers in the United States from the PROST-QA (2003-2006) and the PROST-QA/RP2 cohorts (2010-2013) with a pre-specified goal of comparing RALP (549) and ORP (545). We measured longitudinal patient-reported health-related quality of life (HRQOL) at pre-treatment and at 2, 6, 12, and 24 months, and pathological and perioperative outcomes/complications. RESULTS: Demographics, cancer characteristics, and margin status were similar between surgical approaches. ORP subjects were more likely to undergo lymphadenectomy (89% vs 47%; p <0.01) and nerve sparing (94% vs 89%; p <0.01). RALP vs ORP subjects experienced less mean intraoperative blood loss (192 vs 805 mL; p <0.01), shorter mean hospital stay (1.6 vs 2.1 days; p <0.01), and fewer blood transfusions (1% vs 4%; p <0.01), wound infections (2% vs 4%; p=0.02), other infections (1% vs 4%; p <0.01), deep venous thromboses (0.5% vs 2%; p=0.04), and bladder neck contractures requiring dilation (1.6% vs 8.3%; p <0.01). RALP subjects reported less pain (p=0.04), less activity interference (p <0.01) and higher incision satisfaction (p <0.01). Surgical approach (RALP vs ORP) was not a significant predictor of longitudinal HRQOL change in any HRQOL domain. CONCLUSIONS: In high-volume academic centers, RALP and ORP patients may expect similar long-term HRQOL outcomes. Overall, RALP patients have less pain, shorter hospital stays, and fewer post-surgical complications such as blood transfusions, infections, deep venous thromboses, and bladder neck contractures.

Antiviral Efficacy of Metal and Metal Oxide Nanoparticles against the Porcine Reproductive and Respiratory Syndrome Virus.

Porcine reproductive and respiratory syndrome viruses (PRRSV) are responsible for one of the most economically important diseases affecting the global pig industry. On-farm high-efficiency particulate air (HEPA) filtration systems can effectively reduce airborne transmission of PRRSV and the incidence of PRRS, but they are costly, and their adoption is limited. Therefore, there is a need for low-cost alternatives, such as antimicrobial filters impregnated with antiviral nanoparticles (AVNP). During the past 10 years, tailored intermetallic/multi-elemental AVNP compositions have demonstrated effective performance against human viruses. In this study, a panel of five AVNP was evaluated for viricidal activity against PRRSV. Three AVNP materials: AVNP2, copper nanoparticles (CuNP), and copper oxide nanoparticles (CuONP), were shown to exert a significant reduction (>99.99%) in virus titers at 1.0% (w/v) concentration. Among the three, CuNP was the most effective at lower concentrations. Further experiments revealed that AVNP generated significant reductions in viral titers within just 1.5 min. For an optimal reduction in viral titers, direct contact between viruses and AVNP was required. This was further explained by the inert nature of these AVNP, where only negligible leaching concentrations of Ag/Cu ions (0.06-4.06 ppm) were detected in AVNP supernatants. Real-time dynamic light scatting (DLS) and transmission electron microscopic (TEM) analyses suggested that the mono-dispersive hydrodynamic behavior of AVNPs may have enhanced their antiviral activity against PRRSV. Collectively, these data support the further evaluation of these AVNP as candidate nanoparticles for incorporation into antimicrobial air-filtration systems to reduce transmission of PRRSV and other airborne pathogens.

Differential effect of body mass index by gender on oncological outcomes in patients with renal cell carcinoma.

OBJECTIVES: To investigate the relationship between gender, body mass index (BMI), and prognosis in renal cell carcinoma (RCC) patients. MATERIALS AND METHODS: We retrospectively reviewed 1353 patients with RCC who underwent a partial or radical nephrectomy between 1988 and 2015. The association among sex, BMI, stage, grade, overall survival (OS), and recurrence-free survival (RFS) was analyzed. RESULTS: The median age of the patients was 59.4 ± 11.9 years. Female patients had proportionally lower grade tumors than male patients (Grade I-II in 75.5% vs. 69.3% in women and men, respectively, P = 0.022). There was no relationship between Fuhrman grade and BMI when substratified by gender (p > 0.05). There was a nonsignificant trend toward more localized disease in female patients (p = 0.058). There was no relationship between T stage and BMI when stratified by gender (p > 0.05). Patients with higher BMI had significantly better OS (p = 0.0004 and P = 0.0003) and RFS (P = 0.0209 and P =0.0082) whether broken out by lower 33rd or 25th percentile. Male patients with higher BMI had significantly better OS and RFS rates. However, there was no relationship between BMI and OS or RFS for female patients (P > 0.05). Multivariate analysis of the entire cohort demonstrated that a BMI in the lower quartile independently predicts OS (hazard ratio 1.604 [95% confidence interval: 1.07-2.408], P = 0.022) but not RFS (P > 0.05). When stratified by gender, there was no relationship between BMI and either OS or RFS (P > 0.05). CONCLUSIONS: Increasing BMI was associated with RCC prognosis. However, the clinical association between BMI and oncologic outcomes may be different between men and women.

The prevention of extraction site incisional hernia after robotic-assisted radical prostatectomy.

Extraction site incisional hernia (IH) has been recognized as an important complication in minimally invasive procedures but has not been as well characterized following robotic-assisted laparoscopic prostatectomy (RALP). Approximately 29% of IH required surgical repair. A number of techniques have been utilized to reduce the rates of IH following minimally invasive procedures. First, off-midline extraction was investigated, this did not demonstrate a reduction in incisional hernia rates. Recently, supra-umbilical transverse incisions have been utilized to extract prostate specimen and this method decreased the extraction site IH rate compared to the vertical midline incision. In addition, the choice of fascial closure technique and choice of the suture may influence the incidence of extraction site IH. For example, studies showed that abdominal fascial closure using a nonabsorbable suture and a continuous running suture technique decreased IH rate from 32 to 17%. Finally, "the small bites technique" has been recommended to reduce hernia incidence after midline fascial closure following a randomized controlled trial (RCT) which demonstrated the superiority of the small-bite technique. In summary, a supra-umbilical transverse incision to extract the specimen was shown to decrease the rate of extraction site IH. In vertical midline incisional closure, the small bites technique with slowly- or non-absorbable suture, such as #0 or 2-0 PDS II with SH or CT-2 needle (26 mm arch length), reduces the IH rate. Urologists should consider this data to reduce the risk of IH following RALP.

A modified Delphi study to develop a practical guide for selecting patients with prostate cancer for active surveillance.

BACKGROUND: Active surveillance (AS) is a management option for men diagnosed with lower risk prostate cancer. There is wide variation in all aspects of AS internationally, from patient selection to investigations and follow-up intervals, and a lack of clear evidence on the optimal approach to AS. This study aimed to provide guidance for clinicians from an international panel of prostate cancer experts. METHODS: A modified Delphi approach was undertaken, utilising two rounds of online questionnaires followed by a face-to-face workshop. Participants indicated their level of agreement with statements relating to patient selection for AS via online questionnaires on a 7-point Likert scale. Factors not achieving agreement were iteratively developed between the two rounds of questionnaires. Draft statements were presented at the face-to-face workshop for discussion and consensus building. RESULTS: 12 prostate cancer experts (9 urologists, 2 academics, 1 radiation oncologist) participated in this study from a range of geographical regions (4 USA, 4 Europe, 4 Australia). Complete agreement on statements presented to the participants was 29.4% after Round One and 69.0% after Round Two. Following robust discussions at the face-to-face workshop, agreement was reached on the remaining statements. PSA, PSA density, Multiparametric MRI, and systematic biopsy (with or without targeted biopsy) were identified as minimum diagnostic tests required upon which to select patients to recommend AS as a treatment option for prostate cancer. Patient factors and clinical parameters that identified patients appropriate to potentially receive AS were agreed. Genetic and genomic testing was not recommended for use in clinical decision-making regarding AS. CONCLUSIONS: The lack of consistency in the practice of AS for men with lower risk prostate cancer between and within countries was reflected in this modified Delphi study. There are, however, areas of common practice and agreement from which clinicians practicing in the current environment can use to inform their clinical practice to achieve the best outcomes for patients.

A green wave of saltmarsh productivity predicts the timing of the annual cycle in a long-distance migratory shorebird.

Understanding how migratory animals respond to spatial and temporal variation in habitat phenology is critical for identifying selection pressures and tradeoffs at different life history stages. We examined the influence of breeding habitat phenology on life history timing of the eastern willet (Tringa semipalmata semipalmata) across a latitudinal gradient of breeding sites on the east coast of North America. To describe migration and life history timing, we deployed light-level geolocators on willets at breeding sites in New Jersey, Massachusetts and Maine, USA and evaluated additional data on life history timing and migratory connectivity from previous studies, eBird and band recoveries. Willets from Nova Scotia to Georgia winter exclusively on the Atlantic coast of northern South America and share common stopover sites. The timing of wintering site departure, breeding site arrival, nesting and southbound departure was later for birds breeding at higher latitudes while the duration of all life phases was similar across sites. Regardless of latitude, nesting corresponded with a consistent stage of seasonal salt marsh biomass accumulation and with peak spring temperature acceleration (GDD jerk). Temperature acceleration and salt marsh biomass were closely correlated with each other across the 11° latitudinal gradient we examined and with the timing of nest initiation across the northern 6° of this gradient. For this northern 6° of latitude, these results suggest that the timing of migration and breeding events in the annual cycle of eastern willets is constrained by a phenological "green wave" of spring salt marsh productivity at breeding sites.