Starting Androgen Deprivation Therapy Research Articles

1657TiP The STAMPEDE2 stereotactic ablative body radiotherapy (SABR) trial: A phase III, randomised, open-label trial in patients with newly diagnosed oligometastatic prostate cancer (PC) starting androgen deprivation therapy (ADT)

1657TiP The STAMPEDE2 stereotactic ablative body radiotherapy (SABR) trial: A phase III, randomised, open-label trial in patients with newly diagnosed oligometastatic prostate cancer (PC) starting androgen deprivation therapy (ADT)

1656TiP The STAMPEDE2 niraparib-abiraterone acetate + prednisolone trial: A phase III, randomised, open-label trial in patients with metastatic prostate cancer (mPC) with a deleterious alteration in a homologous recombination repair (HRR) gene starting androgen deprivation therapy (ADT)

1656TiP The STAMPEDE2 niraparib-abiraterone acetate + prednisolone trial: A phase III, randomised, open-label trial in patients with metastatic prostate cancer (mPC) with a deleterious alteration in a homologous recombination repair (HRR) gene starting androgen deprivation therapy (ADT)

Impact of Androgen Deprivation Therapy on Cognitive Function of Elderly Men With Prostate Cancer.

Background Prostate cancer affects millions of men worldwide. Androgen deprivation therapy is the most prescribed medication for elderly men with prostatic cancer to slow and suppress the disease progression. Androgen deprivation therapy works on decreasing testosterone levels, and that can cause multiple side effects, including potential cognitive affection in the form of accelerating cognitive aging and potentially increasing the risk of dementia. This study is aimed at evaluating the impact of androgen deprivation therapy on the cognitive function of elderly men recently diagnosed with prostate cancer. Methods The current research is a prospective cohort study conducted on 85 elderly patients recently diagnosed with prostate cancer who are about to start androgen deprivation therapy within two weeks of the diagnosis. These patients were recruited from the oncology and geriatrics outpatient clinics of Ain Shams University hospitals and were followed up on androgen deprivation therapy for at least six months. Cognitive and depression assessments were done using the Montreal Cognitive Assessment Test and Montreal Cognitive Assessment Test-Basic (according to their education) and the Patient Health Questionnaire-9. The cases were assessed at the start, after two months, and after six months of androgen deprivation therapy use. Cognitively impaired or depressed patients were excluded at the beginning of the study. Results This study showed that 49 out of 85 (57.6%) of the studied participants had a lower Montreal cognitive assessment test score average after six months, indicating mild cognitive impairment. Cognitive domains such as visuospatial, language, and attention were affected. About one-third of the participants were diagnosed with depression after six months of the androgen deprivation therapy. All the depressed participants had cognitive impairment. Conclusion The use of androgen deprivation therapy carries the risk of cognitive decline and regression of some of the cognitive domains such as language, visuospatial, attention, and depression in the elderly with recently diagnosed prostate cancer who received ADT for six months. Conversely, depression could not be linked to cognitive decline. Further research should continue exploring the relationship between cognitive decline and ADT and seek strategies to mitigate these effects, ensuring comprehensive patient care targetingcognitive and psychological well-being.

Abstract 7652: Plasma markers of hemostasis, fibrinolysis, and angiogenesis prior to androgen deprivation therapy (ADT) in progressive prostate cancer (PC) and associations with long-term thrombotic events and survival

Abstract Background: PC is the third most common malignancy associated with thrombosis, procoagulants may play a role in tumorigenesis and progression, and patients (pts) with PC may have activation of the hemostatic system evident in plasma. The prognostic significance of these markers and their relationship to thrombotic events and overall survival (OS) are under-explored. Methods: Patients >18 years were included if they had progressive PC planned to start ADT, were >6 months from surgery or RT, with no history of prior VTE, unexplained bleeding, current or planned anticoagulation, or an additional active malignancy. Plasma samples were obtained via peripheral venipuncture in tubes containing 3.2% sodium citrate and immediately placed on ice. Samples were analyzed for D-dimer, thrombin-antithrombin complex (TAT), IL-6, IL-8, VEGF, and tissue factor (TF) levels by ELISA. Patients had markers drawn at baseline (prior to initiation of ADT), 1 month, and 6 months after initiation. Results: 40 patients were accrued with a median age of 68 years. At baseline, 29 (73%) had presence of metastases. Baseline median PSA was 15 and median PSA doubling time was 0.32. Baseline median hemoglobin was 13.85, platelets were 218, D-dimer was 322 ng/dL, IL-6 was 0 pg/mL, IL-8 was 0 pg/mL, TAT was 3 ug/L, VEGF was 21 pg/mL, and TF was 26 pg/mL. Median follow-up was 78 months. During follow up, 35 (87.5%) had metastases. 10 (25%) had thrombotic events (6 [15%] venous, 4 [10%] arterial) at median 37 months follow up. Median baseline age of pts with subsequent thrombotic events was 74, vs 67 in those without a thrombotic event. While there was no significant difference in baseline PSA between groups with and without clotting events, pretreatment PSA doubling time was significantly lower in pts with subsequent thrombosis (0.27 vs 0.35, p=0.047). Median baseline D-dimer and TF were higher in patients with subsequent thrombosis (D-dimer: 516 vs 282, p=0.10; TF: 36 vs 24, p=0.12). In univariate analysis, baseline IL-6 and VEGF were associated with OS (IL-6: HR=1.05, 95% CI [1.01,1.09], p=0.025; VEGF: HR=1.02, 95% CI [1.00,1.03], p=0.028). When controlling for presence of metastasis, baseline TAT was associated with OS (HR=1.05, 95% CI [1.00,1.11], p=0.055). Conclusions: Plasma markers of hemostatic activation, fibrinolysis, and angiogenesis prior to initiation of ADT are associated with subsequent thrombotic events and overall survival years later. Further analysis will examine how these markers change over time with hormonal therapy. Citation Format: Jessica S. Palmer, Charlene Thomas, Nicole Jacobs, David Nanus, Scott T. Tagawa. Plasma markers of hemostasis, fibrinolysis, and angiogenesis prior to androgen deprivation therapy (ADT) in progressive prostate cancer (PC) and associations with long-term thrombotic events and survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7652.

'Prehabilitation' checklist for men with prostate cancer starting androgen deprivation therapy

Androgen deprivation therapy (ADT) plays an important, integral role in the treatment of prostate cancer; however, it is associated with multiple metabolic and other adverse effects. Making patients aware of these prior to starting ADT and assessing any specific risks during discussions is key to optimising outcomes. A brief checklist for health care professionals to use with patients, such as the one presented here, can aid discussions and facilitate signposting to appropriate specialist services without increasing workload.

Effects of androgen deprivation therapy on elderly men with high-risk prostate cancer: PROSARC observational study

IntroductionProstatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient’s quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. Materials and methodsPROSARC is a national (Spain) prospective observational study (May-2022–May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. ResultsA 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (p=0.666), decreased mean value of appendicular muscle mass (p=0.01) and increased percentage of fat mass (p=0.012). ConclusionIn patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

Racial Disparities in Diagnosis and Treatment of Depression Associated with Androgen Deprivation Therapy for Prostate Cancer

To analyze potential racial disparities in the diagnosis and management of depression associated with androgen deprivation therapy. TriNetX health record network was queried for prostate cancer patients treated with androgen deprivation therapy from 2003-2023. Differences in rates of depression diagnosis and treatment were compared between White and Black patients. Means, odds ratios, and t tests were calculated in univariate analysis with 95% confidence intervals (CI). Data were queried from 93 health care organizations to yield 78,313 prostate cancer patients treated with androgen deprivation therapy. Patients on androgen deprivation therapy had 60% greater odds of developing depression vs other patients [9% vs 6%; odds ratio (OR) 1.6; 95% CI (1.5-1.7); P <.0001]. Of those with depression secondary to androgen deprivation therapy, only 35% were treated with antidepressants. After starting androgen deprivation therapy, White patients had 30% greater odds of being diagnosed with depression, compared to Black patients [10% vs 8%; OR 1.3; 95% CI (1.2-1.4);P <.001]. White patients also had higher odds of being treated with a first line antidepressant than Black patients [56% vs 48%; OR 1.4, 95% CI (1.2-1.6),P <.001]. This analysis confirms a significant association between androgen deprivation therapy and the development of clinical depression, and highlights its medical undertreatment. Importantly, our findings also indicate significant racial disparities in the identification and treatment of depression. Routine screening initiatives that account for social determinants of health may alleviate this disparity. Limitations of this study include retrospective design and lack of data describing severity of depression, which might correlate with need for medication.

Mature results of a phase 2 pilot study of radium-223 and radiotherapy in untreated hormone-naïve men with oligometastatic prostate cancer to bone.

160 Background: We hypothesized that treatment with Radium-223 (Ra223) and to ≤5 sites of bony metastases could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL). Methods: 20 men previously treated with surgery, radiation, or both for M0 PCa later developed ≤5 bone-only mets were eligible for this prospective trial. Inclusion: testosterone ≥ 100 ng/dL and mets on conventional bone scan, validated by a CT, MRI, or PET/CT. Exclusion: LHRH therapies after initial treatment or N1 disease at diagnosis of bone mets. Therapy was 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and q3 months. PSA was evaluated monthly during the Ra223 course and q3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months. Discontinuation of study therapy occurred if: PSA rise &gt; 10% if baseline PSA &gt;20ng/ml, PSA&gt;20 if baseline PSA &lt;20 ng/ml, radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date. Patients were followed for 2 years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as &gt;1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests and univariate Cox regression. Statistical significance was considered at P&lt;0.05. Results: The median number of Ra223 cycles was 6. 6 patients had &lt;6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 months was 50.0% and 40.0%, respectively (p&lt;0.001). Median time to ADT was 15 months. 11 (55%) and 5 (25%) patients had a PSA decline exceeding 50% and 90%, respectively. Two patients had undetectable (PSA&lt;0.01) at 2 years. There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2+ events attributed as possible or likely to Ra-223 were seen in 4 patients (bone pain, fatigue, fracture, decreased WBC count, and other). Grade 2+ events attributed as possible or likely to EBRT were seen in 2 patients, including fatigue and other pain. No differences were noted for age, baseline PSA, days from primary treatment, NCCN risk group, TNM stage, ISUP grade group, BMI, or # of lesions in those who met or failed the primary endpoint (all p&gt;0.05). Conclusions: In this prospective pilot study, the first-line use of Ra223 and SBRT to conventionally imaged oligomets in hormone-naïve men resulted in a significant delay in ADT use compared to historical control. The therapy is well tolerated, maintains QoL, and may result in undetectable PSA. Clinical trial information: NCT03304418 .

Efectos de la privación androgénica en cáncer de próstata de alto riesgo en ancianos: estudio observacional PROSARC

IntroductionProstatic carcinoma (PC) is a frequent neoplasm in elderly patients. Although androgen deprivation is associated with survival benefits, it is also related to adverse effects such as osteoporosis, frailty, or sarcopenia, which can negatively affect the patient's quality of life. This study aims to quantify and evaluate the prevalence of osteoporosis, frailty, or sarcopenia in elderly PC patients before and after androgen deprivation. We present data from an interim analysis. Materials and methodsPROSARC is a national (Spain) prospective observational study (May-2022-May-2025) still in progress in 2 hospitals. It includes patients with high-risk PC, aged ≥70 years, non-candidates for local treatment and scheduled to start androgen deprivation therapy. The following variables are analyzed: comorbidity, frailty (Fried frailty phenotype criteria), osteoporosis, sarcopenia (EWGSOP2), fat mass and muscle mass, before treatment and after 6 months of follow-up. ResultsA 6-month follow-up was completed by 12/25 included patients (mean age, 84 years), with a high baseline prevalence of pre-frailty/frailty (67.7%), sarcopenia (66.7%) and osteoporosis (25%). Treatment did not significantly alter these variables or comorbidity. We observed changes in body mass index (P=.666), decreased mean value of appendicular muscle mass (P=.01) and increased percentage of fat mass (P=.012). ConclusionIn patients with high-risk PC, advanced age and a considerable prevalence of osteoporosis, frailty and sarcopenia, androgen deprivation (ADT; 6 months) produces decreased muscle mass without impact on the incidence of the known adverse effects of androgen deprivation.

1767MO External validation of a digital pathology-based multimodal artificial intelligence (MMAI)-derived model in high-risk localized (M0)/metastatic (M1) prostate cancer (PCa) starting androgen deprivation therapy (ADT) in the docetaxel (Doc) or abiraterone (AAP) phase III STAMPEDE trials

1767MO External validation of a digital pathology-based multimodal artificial intelligence (MMAI)-derived model in high-risk localized (M0)/metastatic (M1) prostate cancer (PCa) starting androgen deprivation therapy (ADT) in the docetaxel (Doc) or abiraterone (AAP) phase III STAMPEDE trials

Metastatic prostate cancer management: 20 years of progress

Since 1940, patients with metastatic prostate cancer were given androgen deprivation therapy alone. In 2013, the addition of docetaxel improved progression-free survival and overall survival in patients with metastatic hormone-sensitive prostate cancer. 1 Gravis G Fizazi K Joly F et al. Androgen-deprivation therapy alone or with docetaxel in non-castrate metastatic prostate cancer (GETUG-AFU 15): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013; 14: 149-158 Summary Full Text Full Text PDF PubMed Scopus (528) Google Scholar , 2 Sweeney CJ Chen YH Carducci M et al. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015; 373: 737-746 Crossref PubMed Scopus (1831) Google Scholar After 2013, the combination of abiraterone acetate plus prednisolone with androgen deprivation therapy increased overall survival, as did the addition of other androgen receptor signalling inhibitors (such as enzalutamide or apalutamide) to standard androgen deprivation therapy. 3 James ND de Bono JS Spears MR et al. Abiraterone for prostate cancer not previously treated with hormone therapy. N Engl J Med. 2017; 377: 338-351 Crossref PubMed Scopus (1091) Google Scholar , 4 Davis ID Martin AJ Stockler MR et al. Enzalutamide with standard first-line therapy in metastatic prostate cancer. N Engl J Med. 2019; 381: 121-131 Crossref PubMed Scopus (734) Google Scholar , 5 Chi KN Chowdhury S Bjartell A et al. Apalutamide in patients with metastatic castration-sensitive prostate cancer: final survival analysis of the randomized, double-blind, phase III TITAN study. J Clin Oncol. 2021; 39: 2294-2303 Crossref PubMed Scopus (124) Google Scholar In 2022, the triple combination of androgen deprivation therapy, docetaxel, and abiraterone or darolutamide showed improved overall survival compared with androgen deprivation therapy plus docetaxel. 6 Fizazi K Foulon S Carles J et al. Abiraterone plus prednisone added to androgen deprivation therapy and docetaxel in de novo metastatic castration-sensitive prostate cancer (PEACE-1): a multicentre, open-label, randomised, phase 3 study with a 2 × 2 factorial design. Lancet. 2022; 399: 1695-1707 Summary Full Text Full Text PDF PubMed Scopus (112) Google Scholar , 7 Smith MR Hussain M Saad F et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer. N Engl J Med. 2022; 386: 1132-1142 Crossref PubMed Scopus (153) Google Scholar Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocolEnzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Full-Text PDF Open Access

Initial results of a phase 2 pilot study of radium-223 and radiotherapy in untreated hormone-naïve men with oligometastatic prostate cancer to bone.

156 Background: We hypothesized that treatment with Radium-223 (Ra223) and to ≤5 sites of bony metastases (mets) could safely delay the time to start androgen deprivation therapy (ADT) and maintain quality of life (QoL). Methods: 20 men previously treated with surgery, radiation, or both for M0 PCa later developed ≤5 bone-only mets were eligible for this prospective trial. Inclusion: testosterone ≥ 100 ng/dL and mets on conventional bone scan, validated by a CT, MRI, or PET/CT. Exclusion: LHRH therapies after initial treatment, or N1 disease at diagnosis of bone mets. Therapy was 6 cycles of Ra223 and SBRT (30 Gy in 5 fractions between cycles 1-2). Bone scan was performed at baseline and q3 months. PSA was evaluated monthly during the Ra223 course, and q3 months after. Therapeutic effectiveness was defined as ≥20% of patients meeting the primary endpoint of freedom from ADT (FFAdt) use at 15 months. Discontinuation of study therapy occurred if: PSA rise &gt; 10% if baseline PSA &gt;20ng/ml, PSA&gt;20 if baseline PSA &lt;20 ng/ml, radiographic progression or a skeletal-related event (SRE). All endpoints were timed from the Cycle 1 radium date. Patients were followed for 2 years. Clinically significant changes in patient-reported outcome (PRO) measures were defined as &gt;1/2 standard deviation from the mean baseline value and were censored after the time of ADT use. Continuous and categorical covariates were compared using the Wilcoxon rank sum and Pearson’s Chi2 tests, respectively, and univariate Cox regression. Statistical significance was considered at P&lt;0.05. Results: The median number of Ra223 cycles was 6. 6 patients had &lt;6 cycles (range 2-5) due to progression. FFAdt at 15 and 24 Months was 49.5% and 38.5%, respectively (p&lt;0.001). The median time to ADT was 14.8 months. There were no significant changes from baseline in any PRO QoL domain (physical functioning, anxiety, depression, fatigue, satisfaction with participation in social roles, sleep disturbance, and pain interference). There were 2 patients with Grade 3 SREs (bone fracture, pain). Grade 2+ events attributed as possible or likely to Ra-223 were seen in 4 patients (bone pain, fatigue, fracture, decreased WBC count, and other). Grade 2+ events attributed as possible or likely to EBRT were seen in 2 patients and included fatigue and other pain. were noted for age, baseline PSA, days from primary treatment, NCCN risk group, TNM stage, ISUP grade group, BMI, or # of lesions in those who met or failed the primary endpoint (all p&gt;0.05). Conclusions: First-line use of Ra223 and SBRT to oligomets in hormone-naïve men in this prospective pilot study resulted in a significant delay in ADT use compared to historical control, is well tolerated, and maintains QoL. Clinical trial information: NCT03304418 .

Improving bone health in prostate cancer patients starting androgen deprivation therapy: does Fracture Risk Assessment Tool (FRAX®) enhance stratification and targeted management?

Long-term use of androgen deprivation therapy (ADT) in prostate cancer patients results in increased bone turnover and decreased bone mineral density (BMD). Proper assessment of any existing osteoporotic fracture risk is crucial prior to starting treatment. However, this risk assessment is poorly performed in these patients in spite of available validated tools including the Fracture Risk Assessment Tool (FRAX®). The objective of this study was to assess the distribution of osteoporotic fracture risk in a cohort of men commencing ADT for prostate cancer using the FRAX® algorithm. Between July 2020 and May 2022, 200 men filled in the FRAX® questionnaire just before ADT. They were stratified into the high-risk (> 20% probability of a MOF over the next 10years), intermediate-, and low-risk categories for fragility fractures. We also measured their serum vitamin D and calcium levels. The average age was 73.5years (54-89). It took less than 10min to complete the assessment. Only six patients were at high-risk, were started on bisphosphonates immediately, and referred for a dual energy X-ray absorptiometry (DEXA) scan. Twelve patients in the intermediate-risk category were referred for DEXA scans for bone mineral density measurements. A total of 182 patients (91%), were in the low-risk category and given lifestyle advice only. All had normal calcium levels but 134 (67%) patients, mostly in the low-risk category, had reduced vitamin D levels (< 50nmol/L). The FRAX® questionnaire is simple and immediately identifies patients who are at risk of fragility fractures. Our study has demonstrated that the majority of men (91%) in our cohort commencing ADT for prostate cancer were considered low risk for future osteoporotic fracture. We were surprised that more than half of our patients had low vitamin D levels.

LBA62 Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

LBA62 Comparison of abiraterone acetate and prednisolone (AAP) or combination enzalutamide (ENZ) + AAP for metastatic hormone sensitive prostate cancer (mHSPC) starting androgen deprivation therapy (ADT): Overall survival (OS) results of 2 randomised phase III trials from the STAMPEDE protocol

1358O Clinical qualification of transcriptome signatures for advanced prostate cancer (APC) starting androgen deprivation therapy (ADT) with or without abiraterone acetate and prednisolone (AAP): An ancillary study of the STAMPEDE AAP trial

Addition of AAP to ADT is standard of care for APC (metastatic, M1 and high-risk non-metastatic, M0). We tested transcriptome signatures as prognostic and predictive biomarkers for patients (pt) starting ADT +/- AAP.

This Month in Adult Urology

This Month in Adult Urology

Proliferation index and survival in men with prostate cancer starting long-term androgen deprivation therapy in the STAMPEDE clinical trial.

5076 Background: Treatment intensification with docetaxel or abiraterone improved survival for advanced prostate cancer starting androgen deprivation therapy (ADT) in the Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy (STAMPEDE, NCT00268476) trial. However, survival and time-to-progression is highly variable on ADT, introducing the risk of unnecessary toxicity from additional treatments for some patients. Here we test the prognostic association of proliferation index using Ki67 scores in the control arm of the STAMPEDE population of high-risk localised (M0) and metastatic (M1) prostate cancer. Methods: Pre-ADT diagnostic needle biopsies were obtained from 517 men randomized in STAMPEDE arm A between 2006 and 2015. These were assessed for proliferation using an analytically optimised Ki67 immunohistochemistry assay. Ki67 was tested for associations with baseline clinico-pathological variables (Grade group, pre-ADT serum PSA and imaging metastatic burden) in univariable linear-regression models, and for associations with survival outcomes in multivariable Cox-regression models adjusted for these and additional confounding variables. Primary outcome measure was overall survival, secondary outcomes were prostate cancer-specific, failure-free, progression-free and metastatic progression-free survival. Results: Ki67 was available for 475 patients who received ADT only for at least 2 years ± radiotherapy. Of 202 M0, 74 were node positive. Of 273 M1, 116, 127 and 30 were respectively low, high and unknown radiological M1 volume. Ki67 score associated with higher Gleason (p=7.15x10-11) and presence of extra-pelvic metastases (p=1.41x10-8). Increasing Ki67 scores showed a strong linear association with poorer overall survival, with an estimated 2% increase in the hazard of death per percentage increase in the score (adjusted HR=1.02, 95% CI 1.01-1.02; p=1.04x10-5). There was also strong evidence that Ki67 associated positively with all secondary outcomes, including prostate cancer-specific survival (adjusted p=5.50x10-6) and metastatic progression-free survival (adjusted p=3.50x10-9). Conclusions: Ki67 immuno-score is strongly prognostic in clinically advanced prostate cancer independent of Gleason score and the other clinicopathological variables tested in this study. Ki67 is a clinically scalable assay that could improve selection for treatment intensification and provide a tool for screening patients most likely to benefit from further molecular investigation.

Late Onset of Abiraterone Severe Hypokalemia Due to Unsuspected ACTH-Secreting NEC

Clinical Case: 68-year-old male, Active smoker (30-40 packs/year), and moderate alcohol drinker. An increase in urinary frequency, nocturia, and a PSA of 116 µg/L led to the diagnosis of disseminated castration-sensitive prostate cancer (CSPC), advanced Gleason score (3 + 4 pT2), with bone and retroperitoneal metastases (CT). By 02/2018, he started androgen deprivation therapy (ADT) with Abiraterone (AB) 1000 mg, prednisone, and LHRH agonist. 15 months later, PSA levels decreased to 0.75 ng/ml without side effects and normal K+(3.7 mEq/L), when a CT scan revealed both liver and bone metastasis. During the progression study, two months later, the patient was admitted to the hospital for severe hypoK+ (1.7 mEq / L), normal renal function and metabolic alkalosis. Although abiraterone was discontinued, up to 460 mEq iv per day of K+ and spironolactone were required to maintain serum K+ above 2.5. 3 days later, the hormonal study revealed TSH 1.13 mU /L, ACTH 162 pmol/L, cortisol 258 nmol/L, aldosterone 105 pmol/L, renin (protein) 0.7 µU/mL and deoxycorticosterone 507 pmol/L. 11 days later, plasma cortisol was 967 nmol/L, ACTH 132pmol/L, and cortisoluria 1456 nmol/d. The suppression test with 1 mg of DXM for cortisol was 1162,5 nmol/L. DHEAS was < 407 nmol/L. Liver biopsy showed a small cell neuroendocrine carcinoma (NEC), chromogranin (+), synaptophysin (+), CD56 (+), TTF-1 (+), PSA (-), Ki-67 90% and the granular cytoplasmic ACTH (+). The octreotide scan (+) revealed pathological uptake in L4, multiple uptakes in the liver, and in the axial skeleton. Treatment with Carboplatin plus Paclitaxel for NEC was started, completing 3 weekly doses with good tolerance and clinical benefit, but with the persistence of severe hypoK+ (2.5 mEq/L). Treatment with lanreotide 120 mg every 4 weeks was added, following a feeling of clinical improvement, the disappearance of edema, asthenia, and normalization of plasma K+ (3,4mEq/L). The patient died two months later from respiratory sepsis. Discussion: Several clinical trials have demonstrated that the combination of AB plus ADT prolongs overall survival in DCSPC. The CYP17 inhibition by AB increases ACTH leading to early secondary mineralocorticoid excess with hypokalemia and hypertension while the cortisol levels remain normal or low. Cortisol serum levels increased after AB was discontinued, whereas aldosterone serum levels remained low due to K+ regulatory feedback. The hormonal profile and the pathological and radiological studies revealed an ACTH-producing small cell NEC. In this patient, the previous treatment with BA has masked the clinical and hormonal profile of an ectopic Cushing syndrome. Therefore, Cyp17 inhibitors can mask adrenal or extra-adrenal processes characterized by alterations in steroid metabolism. This case has suggested a more thorough assessment of the adrenal hormonal profile including ACTH during BA treatment.

OLI-P: Toxicity and efficacy of local ablative radiotherapy in PSMA-PET staged, oligometastatic prostate cancer—A phase II trial.

115 Background: After curative primary therapy, a subset of patients with prostate cancer will have PSA-progression. Modern imaging methods may detect patients with oligometastastic disease at an early time point. Local ablative therapy has shown to improve time to progression compared to standard of care. PSMA-PET hybrid imaging is an emerging method, with a high accuracy and sensitivity to detect oligometastatic disease at low PSA-levels. Methods: At two German centers, patients with PSA progression after local curative treatment had PSMA-PET- hybrid imaging. Patients with up to five PSMA-PET positive metastases were offered to participate in the clinical trial. Further relevant exclusion criteria were ongoing androgen deprivation therapy (ADT), PSA &gt;10 ng/ml or severe comorbidity. The patients had a local ablative radiotherapy (aRT) to all PSMA-PET positive metastases. The primary endpoint was toxicity within two years after aRT. Secondary endpoints included PSA-progression free survival (defined as PSA nadir +1 ng/ml or start of ADT) and therapy-free survival (i.e. time to start ADT). Results: Between 2014 and 2018, 72 patients were included; patients’ characteristics are shown in table. Nine patients were excluded as no aRT was performed. The median follow up for the remaining 63 patients was 34.2 months. Within two years, 67 % (42 of 63 pats) had no report of adverse events. Following events were recorded during follow up: rectal bleeding (Grade 1, n=1), stroke (1), urinary incontinence (grade 2: n=3) secondary malignoma (n=5, primary liver tumor (n=2), bladder cancer, acute leukemia and head and cancer). All adverse events were considered as “not related“ to aRT of the metastases. PSA progression occurred in 44 patients after a median of 14.4 months. After two years, PSA relapse free survival was 38.2 %. ADT was initiated in 36 patients after a median of 26 months; 54 % (n=34 of 63) did not start ADT within two years after aRT. Conclusions: Local ablative radiotherapy in selected patients with PSMA-PET staged oligometastatic prostate cancer is well tolerated and may improve midterm outcome and delay onset of systemic therapy. Clinical trial information: NCT02264379. [Table: see text]

Local and metastatic curative radiotherapy in patients with de novo oligometastatic prostate cancer

The aim of this observational study is to investigate whether local consolidative treatment delivered to the primary site and metastatic tumour burden may add survival benefit to de novo oligometastatic prostate cancer (Oligo-PCa) patients. We retrospectively reviewed all Oligo-PCa patients treated with radiotherapy to the primary tumor sites and metastatic tumor burden at our institution between March 2010 and June 2019. All patients having ≤ 5 metastases involving nodes and/or bones, loco-regional and/or extra-pelvic sites, were included. Most of the patients had started androgen deprivation therapy with or without docetaxel as standard of care before radiotherapy. The Kaplan Meier analysis was performed to estimate survival outcomes. The univariate analysis tested possible prognostic factors increasing the rate of biochemical relapse. We analysed 37 Oligo-PCa patients. Twenty-eight (75.7%) had loco-regional metastases, in 9 patients (24.3%) the metastatic tumour burden was extra-pelvic. Nineteen (51.4%) had bone metastases, 21 (56.8%) nodal involvement and 7 (18.9%) both. Twenty (54.1%) had a single metastasis. The median follow-up was 55.5 months. The median overall survival (OS) was 68.8 months, the 2- and 5-year OS rates were 96.9% and 65.4%. The median biochemical relapse free survival (b-RFS) was 58 months and the 2- and 5-year b-RFS rates were 73.3% and 39.3%. The 2- and 5-year local relapse free survival rates were 93.9% and 83.7%. On the univariate analysis post-treatment PSA level ≤ 1 ng/ml was significantly related with the b-RFS (p = 0.004). Curative approach in Oligo-PCa patients involving both the primary tumor and metastatic sites may be feasible and well tolerate. Many patients presented longer survival and PSA at first follow-up was the most important prognostic factor. Further trials are needed to confirm our results and to evaluate if patients with PSA at first follow-up > 1 ng/ml may benefit from further treatments.