{"product_id":"adding-apalutamide-before-and-after-prostate-surgery-improves-outcomes-in-high-risk-prostate-cancer","title":"Adding Apalutamide Before and After Prostate Surgery Improves Outcomes in High-Risk Prostate Cancer","description":"\u003cp\u003eThe PROTEUS trial, a large international phase 3 study involving 2,109 men with high-risk localized or locally advanced prostate cancer, found that adding the drug apalutamide to standard hormone therapy before and after radical prostatectomy significantly improved cancer control compared with hormone therapy plus placebo. Patients receiving apalutamide had a dramatically higher rate of complete or near-complete tumor disappearance at the time of surgery (8.9% vs. 1.0%) and a better metastasis-free survival rate at 5 years (78.2% vs. 73.5%). Side effects, particularly rash, were more common in the apalutamide group, but the drug delayed recurrence, the need for additional treatment, and the spread of cancer.\u003c\/p\u003e\n\n\u003ch1\u003eAdding Apalutamide Before and After Prostate Surgery Improves Outcomes in High-Risk Prostate Cancer\u003c\/h1\u003e\n\n\u003ch2\u003eTable of Contents\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003e\u003ca href=\"#ddn-key-points\"\u003eKey Points\u003c\/a\u003e\u003c\/li\u003e\n\n  \u003cli\u003e\u003ca href=\"#background\"\u003eUnderstanding the Problem: High-Risk Prostate Cancer\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#study-design\"\u003eStudy Design: A Large, Rigorous Trial\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#participants\"\u003eWho Was in the Study?\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#surgery-results\"\u003eKey Finding 1: Tumor Response at the Time of Surgery\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#metastasis-results\"\u003eKey Finding 2: Metastasis-Free Survival\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#secondary\"\u003eSecondary Outcomes: Delaying the Next Treatment\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#safety\"\u003eSafety and Side Effects\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#implications\"\u003eWhat This Means for Patients\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#limitations\"\u003eStudy Limitations\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#recommendations\"\u003eRecommendations\u003c\/a\u003e\u003c\/li\u003e\n  \u003cli\u003e\u003ca href=\"#ddn-faq\"\u003eFrequently Asked Questions\u003c\/a\u003e\u003c\/li\u003e\n\u003cli\u003e\u003ca href=\"#source\"\u003eSource Information\u003c\/a\u003e\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003c!-- ddn:keypoints:start --\u003e\n\u003ch2 id=\"ddn-key-points\"\u003eKey Points\u003c\/h2\u003e\n\u003cul\u003e\n\u003cli\u003eIn the PROTEUS trial of 2,109 men, adding apalutamide to hormone therapy before and after prostate surgery improved cancer control.\u003c\/li\u003e\n\u003cli\u003eApalutamide increased the rate of no or minimal residual cancer at surgery from 1.0% to 8.9%.\u003c\/li\u003e\n\u003cli\u003eFive-year metastasis-free survival improved from 73.5% with placebo to 78.2% with apalutamide.\u003c\/li\u003e\n\u003cli\u003eApalutamide delayed recurrence and the need for additional treatment by about 19 and 33 months, respectively.\u003c\/li\u003e\n\u003cli\u003eSevere side effects, mainly rash, were more common with apalutamide (39.6% vs. 31.0%).\u003c\/li\u003e\n\u003c\/ul\u003e\n\u003c!-- ddn:keypoints:end --\u003e\n\n\n\u003ch2 id=\"background\"\u003eUnderstanding the Problem: High-Risk Prostate Cancer\u003c\/h2\u003e\n\n\u003cp\u003eProstate cancer is not one disease. Some men have slow-growing tumors that may never cause harm. Others have aggressive, high-risk cancer that can return after treatment and spread to other parts of the body. This study focuses on that second group: men with high-risk localized or locally advanced prostate cancer. These men face a much greater risk of recurrence and death than patients with low-risk disease, even when they receive curative-intent treatment with radical prostatectomy (complete surgical removal of the prostate) or radiation therapy combined with androgen-deprivation therapy (ADT, also called hormone therapy).\u003c\/p\u003e\n\n\u003cp\u003eThe numbers are sobering. Despite more than a century of progress in prostatectomy, relapse (the cancer coming back) occurs within 5 years in up to 50% of patients who undergo radical prostatectomy. Up to 20% of these patients die within 10 years, according to prior research cited in the study.\u003c\/p\u003e\n\n\u003cp\u003eThe term \"high risk\" has a specific definition. The National Comprehensive Cancer Network (NCCN) defines high-risk prostate cancer as having at least one of these features:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eA Gleason score of 8 or higher (scores range from 6 to 10, with higher scores indicating more aggressive disease)\u003c\/li\u003e\n  \u003cli\u003eA prostate-specific antigen (PSA) level of 20 ng per milliliter or higher\u003c\/li\u003e\n  \u003cli\u003eA clinical disease stage of T3 (meaning the tumor has grown beyond the prostate capsule)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eFor decades, doctors have hoped that giving systemic therapy (drugs that travel through the whole body) before and after surgery — known as perioperative treatment — could improve cure rates, the way it does for many other cancers. However, this approach has not shown benefit in prostate cancer until now. Earlier trials of neoadjuvant therapy (treatment given before surgery) were hampered by the inclusion of patients with low-risk disease and by the use of primary end points such as PSA response, which do not reliably predict long-term outcomes. The results were not practice-changing.\u003c\/p\u003e\n\n\u003cp\u003eIn the past decade, a series of phase 2 randomized trials of neoadjuvant androgen-receptor pathway inhibitors (drugs that block the male hormone signals that fuel prostate cancer growth) showed a favorable safety profile and encouraging prostate tumor response. Cancer disappearance at surgery was measured by two key indicators: pathological complete response (no cancer cells found in the removed tissue) and minimal residual disease (only a tiny amount of cancer left). These findings set the stage for the current trial.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eApalutamide\u003c\/strong\u003e is an oral nonsteroidal androgen-receptor inhibitor. That means it blocks the androgen receptor, the protein on prostate cancer cells that receives signals from male hormones (androgens) such as testosterone. It is already approved for treating two advanced forms of the disease: nonmetastatic castration-resistant prostate cancer (prostate cancer that progresses even when testosterone levels are extremely low) and metastatic castration-sensitive prostate cancer (cancer that has spread and still responds to hormone therapy). These approvals were based on the SPARTAN and TITAN trials, respectively. In patients with metastatic, castration-sensitive prostate cancer, treatment with ADT plus apalutamide led to rapid, deep, and durable declines in PSA levels and better overall survival than ADT plus placebo.\u003c\/p\u003e\n\n\u003cp\u003eThis trial — called PROTEUS — was designed to test whether giving apalutamide together with ADT before and after surgery could improve outcomes for men with high-risk localized prostate cancer.\u003c\/p\u003e\n\n\u003ch2 id=\"study-design\"\u003eStudy Design: A Large, Rigorous Trial\u003c\/h2\u003e\n\n\u003cp\u003ePROTEUS was a phase 3, double-blind, randomized, placebo-controlled trial. This is the gold standard of medical research design. \"Double-blind\" means neither the patients nor the doctors knew who was receiving the active drug and who was receiving an identical-looking placebo (inactive pill). The trial was conducted at \u003cstrong\u003e184 sites in 18 countries\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003ePatients were randomly assigned in a 1:1 ratio (like a coin flip) to one of two groups:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eADT plus apalutamide\u003c\/strong\u003e (240 mg taken orally once daily)\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eADT plus placebo\u003c\/strong\u003e (a matched inactive pill once daily)\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe treatment schedule was carefully structured. Patients received six cycles of neoadjuvant treatment (each cycle lasting 28 days) before surgery. The study drug (apalutamide or placebo) was stopped from \u003cstrong\u003e2 weeks before radical prostatectomy\u003c\/strong\u003e to \u003cstrong\u003e4 weeks after prostatectomy\u003c\/strong\u003e. After surgery, patients received six more cycles (28 days each) of adjuvant treatment (treatment given after surgery). ADT was continuous throughout the treatment phase. The ADT used was a gonadotropin-releasing hormone analogue (either an agonist or an antagonist), which works by suppressing the testicles' production of testosterone. All patients also underwent pelvic lymph-node dissection (removal of lymph nodes in the pelvis) as part of their surgery.\u003c\/p\u003e\n\n\u003cp\u003eThe trial had \u003cstrong\u003etwo primary end points\u003c\/strong\u003e (the main outcomes being measured):\u003c\/p\u003e\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePathological complete response or minimal residual disease\u003c\/strong\u003e — a composite end point. This was defined as the presence of a minimal residual tumor of no more than 5 mm (in the greatest dimension of the largest tumor lesion) in prostate-confined disease (stage ypT2 or lower), or no identifiable tumor at all (stage ypT0). The prefix \"yp\" indicates the stage was determined after neoadjuvant treatment. Pathologists made these assessments using hematoxylin and eosin staining, with immunohistochemical analysis (NKX3.1, CAM5.2, and PIN4 cocktail staining) as needed. All pathology was reviewed by blinded independent central review.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eMetastasis-free survival\u003c\/strong\u003e — the time from randomization to the first occurrence of distant metastasis (cancer spreading to distant parts of the body) or death from any cause. Distant metastasis was detected on conventional imaging (computed tomography, magnetic resonance imaging, or bone scan) or on prostate-specific membrane antigen positron-emission tomography (PSMA PET, a highly sensitive type of scan). The use of PSMA PET was allowed starting in protocol amendment 7, adopted on April 14, 2022.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eSecondary end points, tested in a hierarchical order, included event-free survival (time from randomization to biochemical failure, local or regional recurrence, distant metastasis, or death), time to the first subsequent local or systemic treatment, time to distant metastasis, freedom from disease at 4 years, metastasis-free survival as assessed with conventional imaging alone, and PSA-free survival with recovery of testosterone to at least 200 ng per deciliter.\u003c\/p\u003e\n\n\u003cp\u003eExploratory end points included low residual cancer burden (≤0.25 cm³ of residual disease in the prostate in organ-confined tumors without lymph-node involvement and with negative surgical margins), castration-resistant prostate cancer, testosterone recovery, and overall survival.\u003c\/p\u003e\n\n\u003cp\u003eThe trial was designed by the sponsor, Johnson \u0026amp; Johnson, with input from the protocol steering committee and health authorities. An independent data-monitoring committee monitored safety and reviewed efficacy. All patients provided written informed consent, and the trial was conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki.\u003c\/p\u003e\n\n\u003cp\u003eStatistical planning was rigorous. A sample size of 2,000 was estimated to give the trial \u003cstrong\u003e94% power\u003c\/strong\u003e to detect a between-group difference of 5 percentage points in the rate of pathological complete response or minimal residual disease, assuming rates of 10% in the apalutamide group and 5% in the placebo group. For the final metastasis-free survival analysis, 477 end-point events were estimated to provide \u003cstrong\u003e85% power\u003c\/strong\u003e to detect a 25% between-group difference in the risk of distant metastasis or death (a hazard ratio of 0.75). Patients were stratified according to region (Europe, North America, or rest of the world), locoregional lymph-node involvement (N0 vs. N1), and Gleason score (7 vs. 8 to 10).\u003c\/p\u003e\n\n\u003ch2 id=\"participants\"\u003eWho Was in the Study?\u003c\/h2\u003e\n\n\u003cp\u003eBetween July 15, 2019, and June 30, 2022, the trial enrolled 2,109 men with newly diagnosed high-risk localized or locally advanced prostate cancer who were candidates for radical prostatectomy. Of these, \u003cstrong\u003e1,057 were assigned to receive ADT plus apalutamide\u003c\/strong\u003e and \u003cstrong\u003e1,052 to receive ADT plus placebo\u003c\/strong\u003e. At the clinical cutoff date (February 2, 2026), the median follow-up was \u003cstrong\u003e61.7 months\u003c\/strong\u003e (just over 5 years).\u003c\/p\u003e\n\n\u003cp\u003ePatient retention was strong. As of the cutoff date, 899 patients (85.1%) in the apalutamide group and 922 (87.6%) in the placebo group remained in the trial. The two groups were well balanced in terms of demographics and disease characteristics. The median age of the patients was \u003cstrong\u003e66 years\u003c\/strong\u003e (interquartile range, 61 to 71).\u003c\/p\u003e\n\n\u003cp\u003eKey characteristics of the study population included:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGleason score:\u003c\/strong\u003e 95.8% of patients had a Gleason score of 8 or higher; 57.8% had a Gleason score of 9, and 4.3% had a score of 10. Only 4.2% had a score of 7 (the lowest allowed under the trial's risk criteria for this group).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTumor stage:\u003c\/strong\u003e 35.5% had a clinical tumor stage of T3 or T4, meaning the cancer had grown through or beyond the prostate capsule. Most patients (44.3%) had stage T2 disease (confined to the prostate).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eLymph-node involvement:\u003c\/strong\u003e 12.3% had clinical lymph-node metastases (stage N1), meaning cancer had spread to lymph nodes within the pelvis.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePSA level:\u003c\/strong\u003e The median PSA level was 14.8 ng per milliliter (interquartile range, 8.1 to 31.5). Forty percent of patients had a PSA of 20 ng\/mL or higher at baseline.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRace and ethnicity:\u003c\/strong\u003e The overall population was 69.4% White, 19.3% Asian, and 3.7% Black, with 6.5% not reported. Among the 431 patients from North America, 44 (10.2%) were Black.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePerformance status:\u003c\/strong\u003e 96.6% of patients had an Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 (fully active), and 3.4% had a score of 1 (restricted in physically strenuous activity but ambulatory).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eGeographic region:\u003c\/strong\u003e 52.9% were enrolled in Europe, 20.4% in North America, and 26.6% in the rest of the world.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eAll patients who underwent randomization were included in the intention-to-treat population (the standard method of analyzing everyone as assigned, regardless of whether they completed treatment). The safety population included all patients who received at least one dose of apalutamide or placebo — 1,050 patients in each group.\u003c\/p\u003e\n\n\u003ch2 id=\"surgery-results\"\u003eKey Finding 1: Tumor Response at the Time of Surgery\u003c\/h2\u003e\n\n\u003cp\u003eThe first major result concerns what pathologists found when they examined the removed prostate tissue. This is the most direct measurement of whether the drug was shrinking and eliminating the cancer before surgery.\u003c\/p\u003e\n\n\u003cp\u003eThe percentage of patients achieving a \u003cstrong\u003epathological complete response or minimal residual disease was dramatically higher in the apalutamide group: 8.9% vs. 1.0%\u003c\/strong\u003e in the placebo group. In plain terms, about 9 in 100 men who received apalutamide had no cancer or only a tiny speck of cancer (≤5 mm) remaining in the prostate at the time of surgery, compared with about 1 in 100 men in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eThe statistical analysis confirmed this was a real effect, not chance. The odds ratio was \u003cstrong\u003e10.17\u003c\/strong\u003e (95% confidence interval [CI], 5.27 to 19.64; P\u0026lt;0.001). Because an odds ratio can overstate the size of an effect, the researchers also provided the unadjusted relative risk: \u003cstrong\u003e9.36\u003c\/strong\u003e (95% CI, 4.90 to 17.86). A P value of less than 0.001 means there is less than a 0.1% probability that this difference occurred by random chance.\u003c\/p\u003e\n\n\u003cp\u003eOther surgical pathology findings reinforced the benefit. The rate of complete tumor disappearance in the prostate (stage ypT0, meaning no identifiable tumor) was \u003cstrong\u003e5.1% in the apalutamide group (54 of 1,057 patients) vs. 0.4% in the placebo group (4 of 1,052 patients)\u003c\/strong\u003e.\u003c\/p\u003e\n\n\u003cp\u003ePositive surgical margins — meaning cancer cells were found at the edge of the removed tissue, a risk factor for recurrence — were present in only \u003cstrong\u003e20.9%\u003c\/strong\u003e of the apalutamide group compared with \u003cstrong\u003e42.7%\u003c\/strong\u003e of the placebo group. Similarly, disease that had grown beyond the prostate (stage higher than ypT2) was found in 53.1% of the apalutamide group vs. 70.6% of the placebo group. Pathological lymph-node involvement (cancer in the removed pelvic lymph nodes) was similar between groups: 23.3% vs. 24.4%.\u003c\/p\u003e\n\n\u003ch2 id=\"metastasis-results\"\u003eKey Finding 2: Metastasis-Free Survival\u003c\/h2\u003e\n\n\u003cp\u003eThe second primary end point was metastasis-free survival, which measures two things: whether the cancer spreads to distant parts of the body, and whether the patient dies from any cause. This is a clinically meaningful end point because preventing metastasis is the ultimate goal of curative treatment.\u003c\/p\u003e\n\n\u003cp\u003eThe final analysis was performed after \u003cstrong\u003e472 end-point events\u003c\/strong\u003e had occurred (99.0% of the 477 expected events). An event occurred in 215 patients (20.3%) in the apalutamide group and in 257 patients (24.4%) in the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eThe probability of metastasis-free survival at 5 years was \u003cstrong\u003e78.2%\u003c\/strong\u003e (95% CI, 75.3 to 80.8) in the apalutamide group, compared with \u003cstrong\u003e73.5%\u003c\/strong\u003e (95% CI, 70.4 to 76.3) in the placebo group. In other words, about 78 in 100 men treated with apalutamide were alive and free of distant metastasis at 5 years, vs. about 74 in 100 men in the placebo group. The difference was statistically significant, with a \u003cstrong\u003ehazard ratio for distant metastasis or death of 0.80\u003c\/strong\u003e (95% CI, 0.67 to 0.96; P = 0.02). A hazard ratio of 0.80 means that, at any given time point, patients in the apalutamide group were 20% less likely to experience metastasis or death compared with the placebo group.\u003c\/p\u003e\n\n\u003cp\u003eMost distant metastases were detected by the highly sensitive PSMA PET scan: 53.0% of the metastatic events in the apalutamide group and 60.7% in the placebo group were first identified this way. A post hoc analysis showed that 686 patients (64.9%) in the apalutamide group and 755 patients (71.8%) in the placebo group underwent PSMA PET at least once during the trial.\u003c\/p\u003e\n\n\u003ch2 id=\"secondary\"\u003eSecondary Outcomes: Delaying the Next Treatment\u003c\/h2\u003e\n\n\u003cp\u003eThe benefits of apalutamide extended beyond the two primary end points. All three key time-to-event secondary end points significantly favored ADT plus apalutamide over ADT plus placebo (P\u0026lt;0.001 for all comparisons):\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eEvent-free survival:\u003c\/strong\u003e The median event-free survival was \u003cstrong\u003e57.1 months\u003c\/strong\u003e in the apalutamide group vs. \u003cstrong\u003e38.4 months\u003c\/strong\u003e in the placebo group (hazard ratio, 0.71; 95% CI, 0.63 to 0.80). This means the apalutamide group went about 19 months longer, on average, before experiencing biochemical failure (a rising PSA), recurrence, metastasis, or death.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTime to first subsequent treatment:\u003c\/strong\u003e The median time was \u003cstrong\u003e74.2 months\u003c\/strong\u003e in the apalutamide group vs. \u003cstrong\u003e41.5 months\u003c\/strong\u003e in the placebo group (hazard ratio, 0.65; 95% CI, 0.57 to 0.73). Patients in the apalutamide group went nearly 33 months longer before needing additional therapy such as radiation or systemic treatment.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eTime to distant metastasis:\u003c\/strong\u003e This also significantly favored apalutamide (P\u0026lt;0.001), meaning the cancer spread to distant sites later in the apalutamide group.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe study also measured other secondary end points including freedom from disease at 4 years, metastasis-free survival as assessed with conventional imaging alone, and PSA-free survival with testosterone recovery. For patients who develop a biochemical failure after surgery, a rising PSA triggers discussion of subsequent therapy, including adjuvant or salvage radiation therapy, at the discretion of the treating physician.\u003c\/p\u003e\n\n\u003ch2 id=\"safety\"\u003eSafety and Side Effects\u003c\/h2\u003e\n\n\u003cp\u003eEvery treatment has risks, and apalutamide is no exception. Adverse events were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Importantly, the trial was double-blind, meaning neither patients nor doctors knew who was receiving the active drug when side effects were being recorded.\u003c\/p\u003e\n\n\u003cp\u003e\u003cstrong\u003eGrade 3 or 4 adverse events\u003c\/strong\u003e (severe or life-threatening side effects) occurred in \u003cstrong\u003e39.6%\u003c\/strong\u003e of patients in the apalutamide group and in \u003cstrong\u003e31.0%\u003c\/strong\u003e of those in the placebo group. In absolute terms, about 40 in 100 apalutamide patients experienced a severe side effect, vs. about 31 in 100 placebo patients. The difference between the groups was driven primarily by a \u003cstrong\u003ehigher incidence of rash\u003c\/strong\u003e in the apalutamide group. Rash is a known side effect of apalutamide and other drugs in its class.\u003c\/p\u003e\n\n\u003cp\u003eIn addition to standard adverse-event monitoring, the trial protocol included specific safety measures:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003eCardiovascular risk was assessed during screening and before surgery, because ADT is known to affect cardiovascular health.\u003c\/li\u003e\n  \u003cli\u003eThromboprophylaxis (medication to prevent blood clots) was administered on the basis of risk factors and local guidelines, per protocol amendment 4.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThe safety population included all 1,050 patients in each group who received at least one dose of the study medication. These findings emphasize that the decision to use apalutamide should weigh the clear oncologic benefits against the increased risk of side effects, particularly rash.\u003c\/p\u003e\n\n\u003ch2 id=\"implications\"\u003eWhat This Means for Patients\u003c\/h2\u003e\n\n\u003cp\u003eThis trial provides strong evidence that a short course of treatment before and after surgery can meaningfully improve outcomes for men with high-risk localized prostate cancer. The two primary end points — pathological response and metastasis-free survival — both improved, and the secondary end points consistently reinforced the benefit. The size of the effect is notable for a field where previous neoadjuvant trials had failed to change practice.\u003c\/p\u003e\n\n\u003cp\u003eSeveral practical points stand out:\u003c\/p\u003e\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe treatment is time-limited.\u003c\/strong\u003e Patients took apalutamide for a total of 12 cycles (about 11 months of active drug, with a pause around surgery). This is not lifelong therapy; it is a defined perioperative course.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe benefit is measurable.\u003c\/strong\u003e The absolute improvement in 5-year metastasis-free survival was 4.7 percentage points (78.2% vs. 73.5%). The improvement in pathological response was even more dramatic: an 8-fold increase in the odds of having no or minimal residual cancer at surgery.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eThe treatment delays recurrence and additional therapy.\u003c\/strong\u003e On average, patients in the apalutamide group went about 19 months longer without a cancer event and about 33 months longer before needing their next cancer treatment. That delay matters for quality of life.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eSide effects are manageable but real.\u003c\/strong\u003e The increased rate of grade 3 or 4 adverse events (39.6% vs. 31.0%) was driven largely by rash. Patients considering this approach should discuss rash management strategies with their care team.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003cp\u003eThese results may change the standard of care for high-risk localized prostate cancer. Radical prostatectomy alone has historically left many patients with high-risk disease at substantial risk of relapse — up to 50% within 5 years. Adding apalutamide around the time of surgery appears to reduce that risk meaningfully.\u003c\/p\u003e\n\n\u003ch2 id=\"limitations\"\u003eStudy Limitations\u003c\/h2\u003e\n\n\u003cp\u003eLike all clinical trials, PROTEUS has limitations that patients and doctors should understand:\u003c\/p\u003e\n\n\u003cul\u003e\n  \u003cli\u003e\n\u003cstrong\u003eNot a cure for everyone.\u003c\/strong\u003e Even with apalutamide, about 20 in 100 patients still experienced metastasis or death within 5 years, and the pathological response rate of 8.9%, while dramatically better than placebo, means that most patients still had substantial residual cancer at surgery.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eFollow-up duration.\u003c\/strong\u003e The median follow-up was 61.7 months (about 5 years). Overall survival, a key exploratory end point, requires longer follow-up to mature. The trial is ongoing, and longer-term data will be important.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eOdds ratio interpretation.\u003c\/strong\u003e The odds ratio of 10.17 for pathological response overstates the magnitude of the effect compared with the relative risk of 9.36. The researchers explicitly noted this, and the absolute rates (8.9% vs. 1.0%) are the most meaningful numbers for patients.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePSMA PET evolution.\u003c\/strong\u003e The use of PSMA PET was introduced midway through the trial (amendment 7, adopted April 14, 2022). Most distant metastases in both groups were detected by PSMA PET rather than conventional imaging. This means metastasis detection was more sensitive in the later phase of the trial, which could affect how events were captured over time.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAssumptions vs. observed rates.\u003c\/strong\u003e The trial's sample size assumed a pathological response rate of 10% in the apalutamide group and 5% in the placebo group. The actual rates were 8.9% and 1.0%. The difference between groups was larger than assumed, but the absolute rate in the apalutamide arm was slightly lower than the trial designers had predicted.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePatient selection.\u003c\/strong\u003e Trial participants had to be candidates for surgery and able to receive ADT for at least 13 months based on cardiovascular risk. Results may not apply to patients with significant cardiovascular disease or those who are not surgical candidates.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eRacial diversity.\u003c\/strong\u003e Overall, 3.7% of participants were Black. Among North American patients, the proportion was 10.2% (44 of 431). This is a lower representation than in the general U.S. prostate cancer population, where Black men have the highest incidence and mortality rates.\u003c\/li\u003e\n\u003c\/ul\u003e\n\n\u003ch2 id=\"recommendations\"\u003eRecommendations\u003c\/h2\u003e\n\n\u003cp\u003eFor patients with newly diagnosed high-risk localized or locally advanced prostate cancer who are considering radical prostatectomy, this trial offers a new option. Here are practical steps to consider when discussing treatment with your care team:\u003c\/p\u003e\n\n\u003col\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about perioperative therapy.\u003c\/strong\u003e The PROTEUS regimen — 6 cycles of ADT plus apalutamide before surgery, a pause around the operation, then 6 cycles after — is now supported by phase 3 evidence. Ask your urologist and oncologist whether this approach is appropriate for your specific situation.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKnow your risk category.\u003c\/strong\u003e Ask your doctor to confirm your Gleason score, PSA level, and clinical tumor stage. These three factors determine whether you fall into the NCCN high-risk category, which is the group that benefited in this trial.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eDiscuss the side-effect trade-off.\u003c\/strong\u003e The benefit is real but not guaranteed. About 9 in 100 men had no or minimal residual cancer at surgery, vs. 1 in 100 with placebo. The 5-year metastasis-free survival was 78.2% vs. 73.5%. Weigh these numbers against the increased risk of rash and other grade 3 or 4 side effects (39.6% vs. 31.0%).\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003ePlan for rash management.\u003c\/strong\u003e Rash was the main driver of increased side effects in the apalutamide group. Ask your doctor about skincare routines, when to report a rash, and what treatments (such as topical steroids or dose adjustments) are available.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eConsider cardiovascular health.\u003c\/strong\u003e The protocol required that patients be deemed able to receive ADT for at least 13 months based on cardiovascular risk. If you have heart disease or risk factors, a cardiology assessment before starting treatment may be advisable.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eKeep the long-term picture in mind.\u003c\/strong\u003e Median follow-up is about 5 years. Overall survival data are not yet mature. This treatment improves pathological response and metastasis-free survival, but its ultimate effect on how long patients live is still being tracked.\u003c\/li\u003e\n  \u003cli\u003e\n\u003cstrong\u003eAsk about clinical trials.\u003c\/strong\u003e The PROTEUS trial was sponsored by Johnson \u0026amp; Johnson (ClinicalTrials.gov number, NCT03767244). If this regimen is not yet available in your region, or if you are interested in other investigational approaches, ask your doctor about clinical trial options or whether this therapy has been incorporated into local guidelines.\u003c\/li\u003e\n\u003c\/ol\u003e\n\n\u003cp\u003eThe decision to add apalutamide to surgery for high-risk prostate cancer is personal. It requires balancing the clear improvements in cancer control against the real risk of side effects. The PROTEUS trial gives patients and doctors the data they need to make that decision together.\u003c\/p\u003e\n\n\u003c!-- ddn:faq:start --\u003e\n\u003ch2 id=\"ddn-faq\"\u003eFrequently Asked Questions\u003c\/h2\u003e\n\u003ch3\u003eWhat is the PROTEUS trial and who was eligible?\u003c\/h3\u003e\n\u003cp\u003eThe PROTEUS trial was a large phase 3 study of 2,109 men with high-risk localized or locally advanced prostate cancer who were candidates for radical prostatectomy. High-risk was defined by a Gleason score of 8 or higher, a PSA of 20 ng\/mL or higher, or clinical stage T3 or higher.\u003c\/p\u003e\n\u003ch3\u003eWhat treatment did patients receive in the PROTEUS trial?\u003c\/h3\u003e\n\u003cp\u003ePatients were randomly assigned to receive either apalutamide (240 mg daily) plus hormone therapy (ADT) or placebo plus ADT. They received six 28-day cycles before surgery, paused around the operation, then six more cycles after surgery. ADT was given continuously throughout the treatment phase.\u003c\/p\u003e\n\u003ch3\u003eWhat should I ask my doctor about this treatment?\u003c\/h3\u003e\n\u003cp\u003eAsk if you are in the high-risk category that benefited in this trial, and whether perioperative apalutamide is appropriate for you. Discuss the trade-off between improved cancer control and increased side effects, especially rash. Also ask about cardiovascular assessment, since ADT affects heart health.\u003c\/p\u003e\n\u003ch3\u003eShould I get a second opinion before starting apalutamide plus hormone therapy before prostate surgery for high-risk prostate cancer?\u003c\/h3\u003e\n\u003cp\u003eA second opinion can help you weigh the benefits and risks of adding apalutamide to hormone therapy before and after prostate surgery. In the PROTEUS trial, this approach improved 5-year metastasis-free survival from 73.5% to 78.2% and increased the chance of no or minimal residual cancer at surgery from 1.0% to 8.9%. However, severe side effects, especially rash, were more common. A second opinion can confirm your high-risk status and help you decide if this treatment is right for you. Diagnostic Detectives Network provides independent expert second opinions.\u003c\/p\u003e\n\u003c!-- ddn:faq:end --\u003e\n\n\u003ch2 id=\"source\"\u003eSource Information\u003c\/h2\u003e\n\n\u003cp\u003e\u003cstrong\u003eOriginal article title:\u003c\/strong\u003e Perioperative Apalutamide in High-Risk Localized Prostate Cancer\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors:\u003c\/strong\u003e M.-E. Taplin, M. Gleave, N.D. Shore, A. Lopez-Gitlitz, A. Kretschmer, E. Efstathiou, P.L. Nguyen, R. Damião, T. Kamoto, A. Ross, A. Briganti, B.A. Hadaschik, A. Heidenreich, Á. Juárez Soto, H. Ye, G. Gotto, B. Rooney, S.K. Tian, L. Wetherhold, B. Miladinovic, S.A. McCarthy, C.P. Evans, and A.S. Kibel, for the PROTEUS Investigators\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eJournal:\u003c\/strong\u003e The New England Journal of Medicine, 2026; volume 395, pages 546-560\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication date:\u003c\/strong\u003e Published May 31, 2026; print issue August 6, 2026\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eDOI:\u003c\/strong\u003e 10.1056\/NEJMoa2603878\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c\/strong\u003e Johnson \u0026amp; Johnson\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c\/strong\u003e PROTEUS ClinicalTrials.gov number, NCT03767244\u003c\/p\u003e\n\u003cp\u003eThis patient-friendly article is based on peer-reviewed research. The original article contains additional data, tables, and supplementary appendices available at NEJM.org.\u003c\/p\u003e","brand":"DiagnosticDetectives.Com","offers":[{"title":"Default Title","offer_id":47494456606876,"sku":null,"price":0.0,"currency_code":"RUB","in_stock":true}],"url":"https:\/\/diagnosticdetectives.ru\/products\/adding-apalutamide-before-and-after-prostate-surgery-improves-outcomes-in-high-risk-prostate-cancer","provider":"DiagnosticDetectives.Com","version":"1.0","type":"link"}