Citations

5004 Background: Patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) treated continuously with testosterone suppression (TS) plus an androgen receptor pathway inhibitor (ARPI) can experience cumulative toxicity. We conducted this single-arm phase 2 trial (NCT05241860) to test the hypothesis that pts who achieve favorable response to TS + ARPI can have prolonged treatment-free interval with testosterone recovery after treatment interruption (TI). Here we report on the primary endpoint. Methods: Eligible pts had mHSPC by conventional imaging with prostate-specific antigen (PSA) ≥ 5 ng/ml and testosterone ≥ 150 ng/dl prior to starting TS+ARPI, with PSA < 0.2 ng/ml and testosterone < 50 ng/dl at the time of enrollment after having received TS for 540-750 days and ARPI for ≥ 360 days. Prior local therapy, radiation to metastases and docetaxel were permitted. After enrollment, pts discontinued TS and ARPI and were followed with PSA and testosterone levels every 3 months (mo), CT/MRI and bone scan at least every 6 mo, and FACT-P questionnaire for patient-reported outcomes (PROs) every 6 mo. Treatment was resumed for PSA ≥ 5 ng/ml, radiographic change (progressive disease [PD] per RECIST 1.1 on CT/MRI or unconfirmed PD per PCWG3 on bone scan), or prostate cancer-related symptoms. The primary endpoint was proportion of men remaining treatment-free 18 mo after TI with eugonadal testosterone ( > 150 ng/dl). Target enrollment was 75 pts to differentiate 18-mo treatment-free rates of 0.30 (H 0 ) and 0.45 (H a ). Results: Of 79 pts enrolled between 07/2022 and 03/2024, 78 were eligible and underwent TI. Among these 78, median PSA prior to starting TS+ARPI was 19 (range 5-6759), 27 (35%) had high volume disease, 31 (40%) never received local therapy, and 55 (71%) did not receive radiation to metastases. By 18 mo after TI, 67% (52/78) recovered testosterone and 58% (45/78) remained treatment-free; 41% (32/78) remained treatment-free with testosterone recovery (80% CI 33.5-48.9%, one-sided p 0.0249). At median follow-up of 21.2 mo, 35% (27/78) resumed initial TS+ARPI after meeting re-initiation criteria (of whom 1 required treatment switch for PD 9 mo later); 5% (4/78) resumed prior to meeting criteria; 9% (7/78) pursued alternative therapy instead of resuming TS+ARPI per protocol; 5% (4/78) withdrew; 1 died of myocardial infarction prior to resuming treatment. 4 pts died, 1 of prostate cancer. Conclusions: The primary objective was achieved with 41% of favorable responders to TS+ARPI remaining treatment-free with testosterone recovery at 18 mo after TI. Analyses of biomarkers and PROs are in progress, and pts will be followed for long-term outcomes. Support: U10CA180821, U10CA180882, UG1CA189823, https://acknowledgments.alliancefound.org, Veracyte Inc. Clinical trial information: NCT05241860 .

Abstract Background: Up to 68% of patients will experience CIPN. There are no FDA or ASCO recommended therapies. The pain (P), numbness (N), and tingling (T) can persist for month, years or even lifetime. Duloxetine reduces pain scores by 0.6-1.0 on the 0-10 scale but does not help N or T. Scrambler therapy (ST) is a novel form of neuromodulation that uses EKG electrodes on the dermatomes to capture the pain c-fiber receptors, and generate an action potential of “non-pain” information to replace the pain information. It appears to reset central sensitization by altering cerebral blood flow and re-establishing the balance of neuropeptides (e.g., NGF, GDNGF) in the blood (Smith et al NEJM 2023). Yet many professionals and patients are unaware of it. Methods: We reviewed all available studies. Results: Smith et al (2010, VCU) noted a 59% P reduction (5.8 to 2.4 at the end of 10 days (P&lt;0.0001)) in 16 subjects, and 4 had 0 pain at day 10. Pachman et al (2015, Mayo) in 37 subjects showed a 53% P reduction by day 10; a 44% reduction in T; and a 37% reduction in N. In a randomized trial of 50 patients using ST versus TENS (transcutaneous electrical nerve stimulation), Loprinzi et al (2020, Mayo), in a randomized trial, showed more than twice as many ST patients reported a 50% improvement (36-56%) vs. TENS (16-28%). At 8 weeks the reductions were important: 33%P, 28%N, 41%T. In a subsequent crossover trial (Childs 2021) of the TENS patients to ST, 6 of 12 ST patients achieved a 50% reduction in P and T. Smith et al (2021 Hopkins) did a randomized sham-controlled trial with 35 patients but observed no lasting effect; in retrospect, the electrodes and electrode placement were incorrect in this trial. Abdi et al (2024, MDACC) did a Phase II trial of ST in 10 patients and found symptoms of N, T, trouble walking, and disturbed sleep had significant improvements at 6 months. Worst pain was reduced at 6 months by 3 points. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. Wang Z. et al (Hopkins, unpublished data 2025) showed a 60% reduction in pain (6.2 to 2) in twelve subjects, with one achieving complete remission. Strouse et al (2025, UCLA) will soon report similar results in over 60 patients. Wang E. et al (2023, Hopkins) reviewed 1152 patients treated with ST and found just 3 adverse events: one hematoma and two red spots under the EKG electrodes. The only other therapy that reduces all the symptoms of CIPN is spinal cord stimulation (Gupta 2024) but that is invasive, expensive, and can cause a multitude of adverse events. Conclusions: Scrambler Therapy is a safe and effective treatment for the P, N, and T of CIPN with rare and minimal side effects in a syndrome with no other effective treatment. It is hindered by reimbursement ($32/30 minutes, the same as TENS even though the technology is completely different). Scrambler Therapy should become more available in the future. Citation Format: Z. Wang, C. L. Loprinzi, S. Abdi, T. B. Strouse, T. J. Smith. Scrambler Therapy: a safe and effective way to treat chemo-induced neuropathy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-02-17.

PURPOSE Hot flashes are a common side effect reported by men receiving androgen-deprivation therapy (ADT) for the treatment of prostate cancer. We sought to determine whether oxybutynin could improve hot flash symptoms in men with prostate cancer. PATIENTS AND METHODS Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomly assigned to receive either oxybutynin 2.5 mg twice daily, oxybutynin 5 mg twice daily, or matching placebo for 6 weeks. The primary end point was the change in patient-reported hot flash scores since baseline at 6 weeks. Additional outcomes included incidence of adverse events (AEs), changes since baseline in Hot Flash–Related Daily Interference Scale (HFRDIS) scores, and patient-reported symptoms. RESULTS Eighty-eight patients were enrolled, with the 81 participants eligible for final analysis reporting an average of 10.1 (standard deviation [SD], 5.55) hot flashes per day and an average daily hot flash score of 18.2 (SD, 13.5) included in final analysis. On average, patients on the placebo arm, 2.5 mg oxybutynin arm, and 5 mg oxybutynin arm had reductions in hot flashes/day of 2.15, 4.77 ( P = .02), and 6.89 ( P < .001), respectively. Daily hot flash scores for placebo, 2.5 mg oxybutynin, and 5 mg oxybutynin reduced by an average of 4.85, 9.94 ( P = .07), and 13.95 ( P = .002) points, respectively. No treatment-related grade 3+ AEs occurred. HFRDIS total scores improved by 14.2 and 20.7 points in the 2.5 mg ( P = .042) and 5 mg ( P < .01) oxybutynin arms, respectively, compared with a 3.1-point improvement with placebo. CONCLUSION Oxybutynin is superior to a placebo for the management of ADT-associated hot flashes in men with prostate cancer.

TPS5118 Background: Novel androgen receptor pathway inhibitors (ARPIs) improve overall survival (OS) in patients (pts) with metastatic hormone-sensitive prostate cancer (mHSPC) in conjunction with testosterone suppression (TS) relative to TS alone. However, the duration of treatment required to derive clinical benefit is unclear, as is whether continuous treatment is requisite for optimal cancer outcomes. Favorable PSA declines have been associated with prolonged OS in clinical trials testing TS + ARPIs. We thus designed this single-arm Phase 2 trial to test the hypothesis that pts who achieve exceptional response to upfront TS + ARPI can suspend treatment, allowing for T recovery and improvement in quality of life while maintaining favorable clinical outcomes. Methods: Eligible pts had mHSPC by conventional imaging with PSA ≥ 5 ng/ml and T ≥ 150 ng/dl (or not known to have been hypogonadal) prior to starting treatment, have been receiving TS for 540-750 days and ARPI for ≥ 360 days, and have achieved PSA < 0.2 ng/ml (stable or falling for 3 consecutive measurements) with castrate T <50 ng/dl at the time of enrollment. Intermittent ADT for biochemical recurrence prior to mHSPC diagnosis, prior local therapy, prior radiation to metastatic sites, and up to 6 cycles of docetaxel in mHSPC are permitted. Pts who underwent surgical castration, received ARPI prior to mHSPC diagnosis, or are receiving experimental treatment for mHSPC or participating in a clinical trial that does not allow for TS or ARPI interruption are excluded. After enrollment, pts discontinue both TS and ARPI and are followed with PSA and T levels every 3 months, conventional CT/MRI and bone scan at least every 6 months, and FACT-P questionnaire for patient-reported outcomes every 6 months. Treatment re-initiation triggers are PSA increase to ≥ 5 ng/ml, radiographic change (progressive disease per modified RECIST 1.1 on CT/MRI or unconfirmed progressive disease per PCWG3 on bone scan), or symptoms attributable to prostate cancer. Subsequent management is per physician discretion. The primary endpoint is remaining treatment-free with eugonadal T (> 150 mg/dl) 18 months after the start of treatment interruption, with 75 pts to be enrolled to differentiate 18-month treatment free rates of 0.30 (null hypothesis) and 0.45 (alternative hypothesis). Secondary endpoints include time to eugonadal T, duration off treatment, and changes in patient-reported outcomes. Exploratory endpoints include radiographic progression-free survival, time to next treatment, OS, and correlation of tissue- and blood-based biomarkers with clinical endpoints. The study was activated in July 2022 and accrual is ongoing throughout the NCTN. Support: U10CA180821, U10CA180882, UG1CA189823, https://acknowledgments.alliancefound.org , Veracyte Inc. Clinical trial information: NCT05241860 .

LBA12004 Background: Hot flashes are among the most common adverse events impacting quality of life reported by patients receiving androgen deprivation therapy (ADT) for the treatment of prostate cancer. Oxybutynin is an effective therapy for reducing frequency and severity of hot flashes in women. Pilot information supports that this drug may also benefit men with hot flashes related to ADT. Methods: Patients with prostate cancer receiving a stable regimen of ADT with at least 28 hot flashes per week were randomized to receive either oral oxybutynin 2.5 mg twice a day, oxybutynin 5 mg twice a day, or matching placebo doses for 6 weeks. The primary endpoint was the change in patient-reported hot flash scores (determined by multiplying the number of hot flashes by the mean hot flash severity [grade 0: none, 1: mild, 2: moderate, 3: severe, and 4: very severe]) from baseline to 6 weeks, as measured by a daily hot flash diary. A total of 87 patients provided 76% power to reject the null hypothesis of no between-arm mean difference in hot flash score reduction from baseline to 6 weeks, when comparing each oxybutynin arm to the combined placebo arms. This was based on a two-sided contrast estimated from a generalized linear mixed model, α= 0.10, intraclass correlation of 0.50, population standardized mean difference of 0.50, and 10% missing data rate. Results: 88 patients were accrued between 10/28/21 and 12/02/23. Six patients cancelled before starting treatment and one was ineligible, leaving 81 analyzed patients with a median age of 68. Baseline characteristics were balanced between arms with patients reporting an average of 10.15 (SD = 5.55) hot flashes per day and an average daily hot flash score of 18.23 (SD = 13.48) at enrollment. On average, patients on the placebo arm, low dose oxybutynin arm, and high dose oxybutynin arm had reductions of 2.15, 4.77, and 6.89 hot flashes/day, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in hot flashes/day (p < 0.001), as did low dose oxybutynin arm patients (p = 0.02). Daily hot flash scores for the same three protocol arms reduced by an average of 4.85, 9.94, and 13.95 points, respectively. Compared to placebo arm patients, high dose oxybutynin arm patients had a greater reduction in daily hot flash scores (p = 0.002), as did low dose oxybutynin arm patients (p = 0.07). No treatment-related grade 3+ adverse events occurred. The most commonly reported oxybutynin-related grade 2 adverse event was dry mouth. Conclusions: Oxybutynin is superior to a placebo for the management of hot flashes in men associated with androgen deprivation therapy and appears to be well tolerated. Support: UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT04600336 .

Background: The Sepsis-3 guidelines have incorporated serum lactate levels of >2 mmol/L in septic shock definition to account for higher observed mortality. Further evidence is needed to support this threshold in cirrhosis, as well as target mean arterial pressure (MAP) during resuscitation. Methods: This observational cohort study investigated the association between initial serum lactate and resuscitation MAP levels on in-hospital mortality in patients with and without cirrhosis. Patients admitted to the intensive care unit for the treatment of septic shock between 2006 and 2021 in a quaternary academic center were included. Patients with cirrhosis documented on imaging and International Classification of Disease codes (n=595) were compared to patients without cirrhosis (n=575). The association of intensive care unit admission lactate levels and median 2-hour MAP with in-hospital mortality and the need for continuous renal replacement therapy was assessed. The association between median 24-hour MAP and in-hospital mortality was analyzed post hoc. Results: Within the cirrhosis group, admission lactate levels of 2–4 and >4 mmol/L were associated with increased in-hospital mortality compared to lactate <2 mmol/L [adjusted odds ratio (aOR): 1.69, CI: 1.03–2.81, aOR: 4.02, CI: 2.53–6.52]. Median 24-hour MAP 60–65 and <60 mm Hg were also associated with increased in-hospital mortality compared with MAP >65 mm Hg (aOR: 2.84, CI: 1.64–4.92 and aOR: 7.34, CI: 3.17–18.76). In the noncirrhosis group, associations with in-hospital mortality were weaker for lactate 2–4 and >4 mmol/L (aOR: 1.32, CI: 0.77–2.27 and aOR: 2.25, CI: 1.40–3.67) and median 24-hour MAP 60–65 and <60 mm Hg (aOR: 1.70, CI: 0.65–4.14 and aOR: 4.41, CI: 0.79–29.38). Conclusions: These findings support utilizing lactate >2 mmol/L in the definition of septic shock, as well as a target MAP of >65 mm Hg during resuscitation in patients with cirrhosis.

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in the ASCO Guideline Methodology Manual . The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information ( Appendix 1 and Appendix 2 , online only).

Patients with cirrhosis frequently require admission to the intensive care unit as complications arise in the course of their disease. These admissions are associated with high short- and long-term morbidity and mortality. Thus, understanding and characterizing complications and unique needs of patients with cirrhosis and acute-on-chronic liver failure helps providers identify appropriate level of care and evidence-based treatments. While there is no widely accepted critical care admission criteria for patients with cirrhosis, the presence of organ failure and primary or nosocomial infections are associated with particularly high in-hospital mortality. Optimal management of patients with cirrhosis in the critical care setting requires a system-based approach that acknowledges deviations from canonical pathophysiology. In this review, we discuss appropriate considerations and evidence-based practices for the general care of patients with cirrhosis and critical illness.

AbstractObjectiveThe objective was to qualitatively synthesize all reported cases of complications, adverse effects, side effects, or harms arising from the use of scrambler therapy (ST).Methods and DesignA systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Embase, Scopus, Web of Science, United States National Library of Medicine clinical trials registry, and Cochrane Central Register of Controlled Trials databases were searched from database inception to December 10, 2021. Case reports/series, abstracts, retrospective studies, and prospective studies (e.g., open-label trials, randomized controlled trials) pertaining to ST and any description of a complication, adverse effect, side effect, or harm were screened. The search protocol was developed a priori and registered via the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021291838).ResultsA total of six RCTs, 19 prospective open-label trials, and 11 case series / case reports met the inclusion criteria, comprising 1,152 total patients. Two patients experienced contact dermatitis, and one patient reported minor ecchymosis that resolved without intervention. This yielded a composite complication rate of 0.26% (3/1,152). There were zero reported serious adverse events.ConclusionsWhen used in accordance with the treatment protocols described by the United States Food and Drug Administration and device manual, ST is associated with a reported composite complication rate that is orders of magnitude lower than those of invasive neuromodulation devices. ST neuromodulation is a safe alternative for patients who cannot undergo invasive neuromodulation device implantation because of either risk or preference.