Background: PSG is a novel measure to assess treatment response in symptom management. In this multicenter prospective longitudinal observational study, we examined the PSG for 10 common symptoms in patients with advanced cancer, and identified the factors associated with PSG intensity and PSG response. Methods: We enrolled patients with advanced cancer seen at 5 outpatient palliative care clinics (USA, Jordan, Brazil, Chile and India). We assessed the intensity of 10 symptoms using the Edmonton Symptom Assessment Scale at first consultation visit and then a second visit 14-34 days later. We also assessed the PSG by asking patients “At what level would you feel comfortable with this symptom?” using the same 0-10 numeric rating scale for each symptom. Response was defined as symptom intensity ≤ PSG. We used multivariate logistic regression to determine factors associated with PSG intensity and PSG response. Results: 728 patients were enrolled from 5 palliative care clinics. The average age was 57 (range 19-85), 361 (50%) were female, and 29 (31%) were White. The medianPSG was 1/10 for nausea, 2/10 for depression, anxiety, drowsiness, well-being, dyspnea and sleep, and 3/10 for pain, fatigue, and appetite. In multivariate logistic regression, Asian ethnicity (odds ratio [OR] 2.4-8.2, P < 0.001), CAGE positivity (OR 1.7-2.3, P < 0.05) and higher baseline symptom intensity (ORs 1.08-1.15 per point, P < 0.03) were associated with PSG ≥ 2 for essentially all symptoms. At visit 2, 34%-73% of patients had a PSG response, which represents a significant improvement compared to the first visit (P < 0.05 except for depression, drowsiness and well-being). PSG response was associated with baseline PSG intensity (ORs 1.3-1.5 per point, P < 0.001) and ethnicity (P < 0.02) for physical symptoms, and male sex (ORs 1.45-1.65, P < 0.02) for psychological symptoms. Conclusions: PSG was 3 or lower for a majority of patients, and varied according to ethnicity, alcoholism and symptom intensity. PSG response allows clinicians and researchers to tailor treatment goals, while adjusting for individual differences in scale interpretation and factors associated with symptom response.