Hall, Emma C

PURPOSE The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer–specific mortality. RESULTS Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points ( P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer–specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT.

TPS7 Background: Penis cancer is a rare but potentially fatal disease. A limited body of evidence exists on which to base the majority of management decisions for patients with regional nodal metastases. Five-year survival for patients with a single involved inguinal lymph node treated with surgery alone is approximately 80%, whilst it ranges from 0 to 12% for patients with pelvic node involvement (N3). Additional strategies are required for the management regionally-advanced disease. InPACT (NCT02305654) aims to determine prospectively the relative benefits and sequencing of surgery, chemotherapy, and chemoradiotherapy in the management of patients with penis cancer who present with palpable or radiologically evident inguinal lymph node metastases. InPACT addresses the following questions: Is there a role for neoadjuvant therapy and, if so, which of the two options (chemotherapy or chemoradiotherapy) before surgery gives superior outcomes? Among patients whose inguinal node histology predicts a high risk of recurrence, does prophylactic pelvic lymph node dissection (PLND) plus chemoradiation to the inguinal and pelvic fields improve survival compared to chemoradiation alone? Methods: A Bayesian trial design aims to include a wide population of patients and incorporates two randomisations: InPACT-neoadjuvant and InPACT-pelvis. Participants are stratified by disease burden (extent of nodal involvement), by the presence or absence of high-risk radiological features, and by GFR. Participants with high disease burden where neoadjuvant treatment is thought to be indicated are randomised to neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy. Participants with intermediate disease burden are randomised to one of 3 arms: Surgery alone or neoadjuvant chemoradiotherapy followed by surgery, or neoadjuvant chemotherapy prior to surgery. Participants in the low-burden group proceed directly to surgery. Participants with postoperative inguinal node pathology that shows high-risk features may then proceed to InPACT-pelvis where randomisation is between adjuvant chemoradiotherapy ± PLND for those not previously treated with chemoradiotherapy & between PLND & observation for those previously treated with neoadjuvant chemoradiotherapy. The study aims to recruit 200 participants. The primary outcome measure is overall survival, with secondary outcome measures of disease-specific survival, disease-free survival, and freedom from locoregional recurrence and distant metastasis. Feasibility, toxicity, the type/extent of surgical complications, and quality of life will be assessed as secondary endpoints for all the InPACT treatment arms. To October 2021, 65 participants have been recruited with centres open in the UK, US and Canada. Clinical trial information: NCT02305654.