Andrews, Jack

Abstract Skeletal muscle is a major determinant of functional status. The impact of advanced prostate cancer (aPC) systemic therapies on body composition is unknown. We identified aPC patients with serial PET-CTs receiving androgen deprivation therapy (ADT), androgen receptor pathway inhibitors (ARPI), chemotherapy, and/or Lutetium-177. An artificial intelligence algorithm quantified body composition changes from PET-CT images. Linear mixed effects models examined body composition changes over time by treatment type. The algorithm examined 2,342 PET-CTs from 468 patients. On multivariable analysis, ADT was associated with a 9% reduction in muscle density (-1.91 Hounsfield units), ARPIs an additional 6% (-1.4 Hounsfield units), and Lutetium-177 a subsequent 6% (-1.3 Hounsfield units), demonstrating progressive reduction in muscle density across later stages of systemic therapy. This large longitudinal analysis of body composition in aPC patients supports the use of an automated PET-CT algorithm to identify aPC patients on systemic therapy at risk for muscle wasting.

5108 Background: We previously proposed a hybrid framework combining LLMs and rule based algorithm (RBA) for automating risk stratification in locPCa. Herein, we aim to validate the risk stratification agent (RSA) in a prospective cohort, develop & evaluate the treatment recommendation agent (TRA) based on NCCN guidelines, and develop an interactive interface to facilitate clinicians for accurate risk stratification and treatment recommendations at the point of care. Methods: This study included pts with locPCa (2004-2024) presenting at Mayo Clinic with at least 1 positive prostate biopsy and MRI report available. For RSA prospective validation, GPT4 extracted key phenotypic variables (PSA, T stage, prostate volume, number of cores, Gleason patterns, grade group) from unstructured MRI and biopsy reports using a zeroshot prompt. An RBA then classified pts into NCCN risk groups. The agent performance was compared with the treating clinician's documentation and evaluated against gold-standard labels manually annotated by two independent clinicians. For development of TRA, two experiments were performed using GPT4 with and without retrieval-augmented generation (RAG) to generate treatment plans. Generated treatment plans were evaluated using NCCN guideline-informed treatment decision tree based algorithm (DTA). Evaluation metrics, weighted – accuracy (acc) and F1, were computed. A clinician facing interface (lisr.org/risk) was developed to provide accurate risk stratification and treatment plans. Results: A total of 858 pts were included (500 for prospective validation, 358 for treatment recommendations). Prospective validation for RSA demonstrated a higher F1 score of 0.89 compared to the treating clinician (F1: 0.58). Treatment recommendation experiments showed that GPT4 with RAG achieved higher acc (64% full – all correct treatment options and 36% partial – at least 1 correct treatment option) compared to GPT4 alone (35% and 65%, respectively). Sensitivity analysis using DTA-informed GPT4 note generation achieved 94% full acc and 6% partial acc. GPT4 alone generated hallucinated treatment options in 71% of cases, while GPT4 with RAG reduced this to 32%. Conclusions: The multi-agent framework based on LLM and RBA achieves high accuracy in risk stratification and treatment recommendation for locPCa. A multi-agent framework with an interactive interface holds high promise to enable efficient, accurate decision-making, and improve locPCa management at the point of care Performance evaluation. RSA(acc; F1) % TRA(full acc; partial acc) % Clinician RSA* GPT4 RAG+GPT4 DTA+GPT4 Overall 60; 58 89; 89 29; 71 64; 36 94; 6 V. High 94; 33 96; 96 55; 45 69; 31 93; 7 High 46; 52 92; 89 - - - Int. Unf 80; 61 91; 90 5; 95 38; 62 93; 7 Int. Fav 57; 64 84; 87 0; 100 98; 2 100; 0 Low 57; 65 87; 80 100; 0 95; 5 90; 10 V. Low 8; 13 50; 67^ - - - *Statistical significance (p<0.01) except for ^V. Low.

e17168 Background: Prostate cancer is the most prevalent cancer and the second leading cancer related death in men in the USA. Radical prostatectomy represents the mainstay treatment for patients with localized prostate cancer. Management of metastatic disease requires multidisciplinary practice and innovative approach for individualized favorable outcomes. Treatment sequencing in patients with advanced prostate cancer has been reported to impact patient’s response to subsequent treatment as well as overall survival outcomes. Here in, we thought to investigate the impact of prior chemotherapy treatment on PSA response rates to 177Lut PSMA. Methods: We conduct a single center retrospective study including 164 patients diagnosed with advanced prostate cancer and treated with 177Lut PSMA for metastatic hormone resistant prostate cancer. 92 patients received 177Lut PSMA as a salvage treatment late after chemotherapy (group A), and we compared them with 70 patients received 177Lut PSMA early in an adjuvant fashion within 3 months after chemotherapy (group B). Favorable PSA response was defined by 50% or more reduction in PSA value after complete treatment with 177Lut PSMA. Results: Approximately 43 % of patients in (group B) received their 177Lut PSMA within six months. The average number of chemo cycles received by patients of (group B) is between 3 to 6 cycles. Median patients’ age (IQR) 63 years (57.75 - 68), median (IQR) number of cycles of 177Lut PSMA 5 (5 - 6). Statistical analyses were performed to determine any differences in post lut PSA response in both groups of patients. Approximately 49 % of patients in (group A) had favorable PSA response versus 44 % of patients in (group B) (p-value 0.3853). Conclusions: The use of 177Lut-PSMA in the post-chemotherapy setting demonstrated similar outcomes whether administered early or late. These findings suggest that the timing of treatment may not significantly impact its effectiveness, but further research is needed to confirm these results and explore potential optimizations for patient care.

Purpose of review Low-volume prostate cancer is an established prognostic category of metastatic hormone-sensitive prostate cancer. However, the term is often loosely used to reflect the low burden of disease across different prostate cancer states. This review explores the definitions of low-volume prostate cancer, biology, and current evidence for treatment. We also explore future directions, including the impact of advanced imaging modalities, particularly prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scans, on refining patient subgroups and treatment strategies for patients with low-volume prostate cancer. Recent findings Recent investigations have attempted to redefine low-volume disease, incorporating factors beyond metastatic burden. Advanced imaging, especially PSMA PET, offers enhanced accuracy in detecting metastases, potentially challenging the conventional definition of low volume. The prognosis and treatment of low-volume prostate cancer may vary by the timing of metastatic presentation. Biomarker-directed consolidative therapy, metastases-directed therapy, and de-escalation of systemic therapies will be increasingly important, especially in patients with metachronous low-volume disease. Summary In the absence of validated biomarkers, the management of low-volume prostate cancer as defined by CHAARTED criteria may be guided by the timing of metastatic presentation. For metachronous low-volume disease, we recommend novel hormonal therapy (NHT) doublets with or without consolidative metastasis-directed therapy (MDT), and for synchronous low-volume disease, NHT doublets with or without consolidative MDT and prostate-directed radiation. Docetaxel triplets may be a reasonable alternative in some patients with synchronous presentation. There is no clear role of docetaxel doublets in patients with low-volume disease. In the future, a small subset of low-volume diseases with oligometastases selected by genomics and advanced imaging like PSMA PET may achieve long-term remission with MDT with no systemic therapy.

Abstract Introduction Infection remains a persistent complication of penile prosthesis (PP) surgery. Despite popularity of Mulcahy’s PP washout protocol, Betadine has known tissue toxicity. Aim We evaluated PP infection rate based on the type of intraoperative irrigation used, ½ strength Betadine vs vancomycin/gentamicin. Methods We reviewed a prospective database of men undergoing primary, revision, and salvage PPs. No other changes to operative or perioperative techniques occurred after the change in irrigation solution. Univariate and logistic regression analyses were used to evaluate differences in infection rate with use of Betadine vs vancomycin/gentamicin irrigation. Potential confounders were reviewed. Main Outcome Measure The primary outcome was rate of PP infection before and after change of intraoperative irrigation. Results From 2014 to 2018, 217 patients underwent PP placement at our institution by a single surgeon; of whom, 21 (9.7%) experienced an infection (primary = 10 [7.1%], revision = 11 [17.19%], salvage = 0 [0%]). Overall, 152 (70%) received irrigation with Betadine and 65 (30%) with Vancomycin/Gentamicin. Univariate analysis demonstrated significantly increased infection rates with Betadine irrigation (odds ratio [OR]: 4.64, P = .006) and with revision surgery (OR: 2.68, P = .02). Significance of increased infection rate with Betadine was maintained (OR: 9.3; P = .025) after controlling for age, body mass index, Charlson comorbidity index, smoking, diabetes, primary vs revision/salvage, prior penile surgery, use of ectopic reservoir, and adjunctive glanulopexy. Conclusions Changing from intraoperative Betadine to vancomycin/gentamicin solution dramatically reduced infection rates among men undergoing PP placement in both primary and revision cases. We hypothesize that differences in infection rate may relate to the relative toxicity or non-sterile nature of Betadine. Manka MG, Yang D, Andrews J, et al. Intraoperative Use of Betadine Irrigation is Associated With a 9-Fold Increased Likelihood of Penile Prosthesis Infection: Results From a Retrospective Case-Control Study. Sex Med 2020;8:422–427.