Targeted Investigational Treatment Analysis of Novel Anti-androgen (TITAN) study: ultralow prostate-specific antigen decline with apalutamide plus androgen-deprivation therapy.

OBJECTIVE: To assess the association between achievement of prostate-specific antigen (PSA) levels ≤0.2 ng/mL (henceforth 'ultralow') and clinical outcomes in patients in the 'Targeted Investigational Treatment Analysis of Novel Anti-androgen' (TITAN) study (ClinicalTrials.gov Identifier NCT02489318) with metastatic castration-sensitive prostate cancer (mCSPC). PATIENTS AND METHODS: Patients in the TITAN study with mCSPC were randomised to 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy. This post hoc analysis assessed the achievement of a PSA level of 0.2->0.02 ng/mL ('ultralow one' [UL1]) and ≤0.02 ng/mL ('ultralow two' [UL2]) vs >0.2 ng/mL with apalutamide treatment and its association with radiographic progression-free survival (rPFS), overall survival (OS), time to castration-resistant PC (TTCRPC), and time to PSA progression (TTPP). The landmark analysis and Kaplan-Meier methods were used. RESULTS: By 3 months, more patients achieved UL1 and UL2 with apalutamide (38% and 23%) vs placebo (15% and 5%). In the apalutamide-treated patients, UL2 vs PSA >0.2 ng/mL at landmark 3 months was associated with significantly longer rPFS (hazard ratio [HR] 0.28, 95% confidence interval [CI] 0.14-0.54), OS (HR 0.24, 95% CI 0.13-0.43), TTCRPC (HR 0.2, 95% CI 0.11-0.38), and TTPP (HR 0.11, 95% CI 0.04-0.27; nominal P values all <0.001); this association was also observed but less pronounced for UL1. Similar findings were observed at 6 months. Early onset of decline to UL2 by 3 months was associated with improved survival vs PSA >0.2 ng/mL anytime (HR 0.12, 95% CI 0.06-0.22; P < 0.001) in apalutamide-treated patients. CONCLUSIONS: In this post hoc analysis of TITAN, patients with the deepest PSA decline derived the greatest benefit. These results extend our findings of apalutamide efficacy in the overall TITAN population, underscoring the clinical value of PSA kinetics as a marker for treatment efficacy. PATIENT SUMMARY: Patients with metastatic prostate cancer that is sensitive to ongoing hormonal treatment benefited significantly from the addition of apalutamide compared with placebo. Those who achieved rapid and deep PSA reduction had the greatest survival benefit.

Prostate-specific antigen (PSA) decline with apalutamide therapy is associated with longer survival and improved outcomes in individuals with metastatic prostate cancer: a plain language summary of the TITAN study.

WHAT IS THIS SUMMARY ABOUT?: This summary describes the results from an additional (or post hoc) analysis of the TITAN study. The TITAN study looked at whether the prostate cancer treatment apalutamide could be used to treat individuals with metastatic castration-sensitive prostate cancer (or mCSPC). A total of 1052 participants with mCSPC were included in the TITAN study. Treatment with apalutamide was compared with treatment with placebo. All participants received androgen deprivation therapy (or ADT), which is a type of hormone therapy that has been part of the main treatment for mCSPC for many years. The results showed that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT. Apalutamide plus ADT also controlled the growth of the cancer for a longer length of time compared with placebo plus ADT. Additionally, participants who received apalutamide plus ADT experienced a greater reduction in the blood levels of prostate-specific antigen (or PSA), called a deep PSA decline, compared with those who received placebo plus ADT. An additional (or post hoc) analysis was carried out to understand whether a decrease in blood PSA levels, in response to treatment, was associated with improved outcomes, including longer survival time. WHAT WERE THE RESULTS OF THE ADDITIONAL ANALYSIS?: In participants who received apalutamide plus ADT, a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes. WHAT DO THESE RESULTS MEAN FOR INDIVIDUALS WITH MCSPC?: These results demonstrate that individuals with mCSPC can benefit from treatment with apalutamide plus ADT. The association seen between deep PSA decline and the longer survival time and improved outcomes highlights how PSA measurements can be used to help monitor cancer disease evolution in response to treatment. Monitoring PSA levels will assist doctors and other healthcare professionals to understand how effectively a treatment is working for a patient and to tailor their treatment approach to improve PSA decline.

Therapeutic and Surgical Indications for Patients with Penile Cancer in the COVID-19 era.

PURPOSE: The aim of this work is to review and synthesize the existing evidence and recommendations regarding to the therapeutic and surgical indications as well as monitoring of patients with Penile Cancer in COVID-19 era and to propose an action protocol to facilitate decision-making. MATERIAL AND METHODS: A non-systematic review of the literature regarding the management of penile cancer during the COVID-19 pandemic was performed until April 30, 2020. We propose our recommendations based on this evidence. RESULTS: Penile cancer is an uncommon but aggressive disease. Prognosis is determined by several characteristics, being the most important the presence of lymph nodes, in which case, treatment should not be delayed. For these reasons, an initial evaluation is mandatory. Priority classifications, based on the oncological outcomes when treatment is delayed, have been made in order to separate deferrable disease from the one that needs high priority treatment. In penile cancer with low risk of progression, surgical treatment can be delayed, but other options must be considered, like topical treatment or laser therapy. In cases with intermediate risk of progression, surgical treatment may be delayed up to three months, but we must consider radiation therapy and brachytherapy as effective options. When feasible, follow-up should by telemonitoring. CONCLUSIONS: In the COVID-19 era, initial evaluation of the patient is mandatory. Histological diagnosis with local staging is necessary before offering any therapeutic option. In case of superficial non-invasive disease, topical treatment is effective in absence of lymph node involvement. In selected patients, radiotherapy is an organ-preserving approach with good results. Non-deferrable surgical treatment must be performed by an experienced surgeon and as an outpatient procedure when possible. When indicated, iLND should not be delayed since it is decisive for patient survival. Follow-up should be by telemonitoring.

Apalutamide plus androgen deprivation therapy in clinical subgroups of patients with metastatic castration-sensitive prostate cancer: A subgroup analysis of the randomised clinical TITAN study.

BACKGROUND: Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation. METHODS: These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; metachronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models. RESULTS: Of 1052 patients, 63%, 81%, 54%, 27%, 5.7%, and 8.0% had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio = 0.68 [95% confidence interval: 0.53-0.87]; p = 0.002), synchronous/low-volume (0.65 [0.40-1.05]; p = 0.08), metachronous/high-volume (0.69 [0.33-1.44]; p = 0.32) and metachronous/low-volume (0.22 [0.09-0.55]; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease. CONCLUSION: TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC. CLINICAL TRIAL REGISTRATION: NCT02489318.

Therapeutic and surgical indications for patients with penile cancer in the COVID-19 era

ABSTRACT Purpose: The aim of this work is to review and synthesize the existing evidence and recommendations regarding to the therapeutic and surgical indications as well as monitoring of patients with Penile Cancer in COVID-19 era and to propose an action protocol to facilitate decision-making. Material and Methods: A non-systematic review of the literature regarding the management of penile cancer during the COVID-19 pandemic was performed until April 30, 2020. We propose our recommendations based on this evidence. Results: Penile cancer is an uncommon but aggressive disease. Prognosis is determined by several characteristics, being the most important the presence of lymph nodes, in which case, treatment should not be delayed. For these reasons, an initial evaluation is mandatory. Priority classifications, based on the oncological outcomes when treatment is delayed, have been made in order to separate deferrable disease from the one that needs high priority treatment. In penile cancer with low risk of progression, surgical treatment can be delayed, but other options must be considered, like topical treatment or laser therapy. In cases with intermediate risk of progression, surgical treatment may be delayed up to three months, but we must consider radiation therapy and brachytherapy as effective options. When feasible, follow-up should by telemonitoring. Conclusions: In the COVID 19 era, initial evaluation of the patient is mandatory. Histological diagnosis with local staging is necessary before offering any therapeutic option. In case of superficial non-invasive disease, topical treatment is effective in absence of lymph node involvement. In selected patients, radiotherapy is an organpreserving approach with good results. Non-deferrable surgical treatment must be performed by an experienced surgeon and as an outpatient procedure when possible. When indicated, iLND should not be delayed since it is decisive for patient survival. Follow-up should be by telemonitoring.