Apalutamide Trial, SABR Radiotherapy, and New Diagnostics Advance Prostate Cancer Care

Adding the drug apalutamide to standard hormone therapy before and after prostate cancer surgery significantly improved outcomes for men with high-risk disease, according to a large international clinical trial published in The New England Journal of Medicine. Among more than 2,100 patients with newly diagnosed high-risk localized or locally advanced prostate cancer, 8.9% of those who received androgen-deprivation therapy plus apalutamide achieved a pathological complete response or minimal residual disease at the time of surgery, compared with 1% in the placebo group. Metastasis-free survival at five years was 78.2% in the apalutamide group versus 73.5% in the placebo group.

The trial tested a "perioperative" strategy, administering therapy both before and after surgery. Patients in the apalutamide group experienced more adverse events — nearly 40% versus 31% in the placebo group — but the side effects were generally tolerable, with most additional events related to rash. The findings open up a third standard-of-care option for men with locally advanced or high-risk disease: androgen-deprivation therapy plus an androgen receptor inhibitor for six months, followed by surgery. The study was funded by Johnson & Johnson.

In a separate development, NHS England will offer high-powered precision radiotherapy called SABR (stereotactic ablative radiotherapy) to low- and intermediate-risk prostate cancer patients outside of trials, cutting the number of treatment sessions from 20 to five. Of the 55,000 men diagnosed with prostate cancer each year, around 17,500 are deemed low or intermediate risk, and modelling suggests about 3,500 are likely to take up the option. NHS England expects all 48 radiotherapy centres to start offering the treatment within weeks. The national clinical director for cancer said the technology focuses a powerful and precise beam of radiotherapy directly on the cancer, limiting damage to healthy cells, and delivering 15 fewer doses helps men get back to living their lives more quickly. Trials are under way to see if the treatment can be used on high-risk patients.

Research published in The Journal of Nuclear Medicine suggests a noninvasive DNA blood test can identify patients with advanced prostate cancer who are most likely to benefit from radiopharmaceutical therapy and monitor their progress during treatment. The study, which followed 93 patients with metastatic castration-resistant prostate cancer receiving 223Ra dichloride, found that patients with a higher amount of tumor DNA in the blood or specific genetic changes such as TP53, PTEN, and cell cycle pathway alterations had worse outcomes when detected before treatment. Changes in tumor DNA during treatment reflected the disease trajectory and the patient's response to therapy.

A robotic system for performing prostate biopsies, called the Mona Lisa system, combines MRI imaging with real-time ultrasound and creates a three-dimensional model of the prostate. The system navigates the needle to the selected target via a transperineal approach, or through the skin rather than through the rectum, which has been increasingly recommended by urological associations due to a lower risk of infections. The PREVENT study, which included approximately 658 patients, found no infection cases with this approach, compared with a rate of about 1.4% with the traditional transrectal approach. The system can also take multiple samples through the same entry point and uses artificial intelligence to detect needle deviation in real time and automatically correct its progression path, reaching the target with accuracy of a few millimeters.

Evidence from the PARTIQoL trial, which compared proton therapy and intensity-modulated radiation therapy (IMRT) in 450 men with localized prostate cancer, showed:

• Five-year progression-free survival was about 93% with both treatments.
• No meaningful differences emerged in bowel function.
• No meaningful differences emerged in urinary outcomes.
• No meaningful differences emerged in sexual function.
• No meaningful differences emerged in hormonal adverse effects.

Proton therapy frequently costs substantially more than IMRT, and the NCCN's inclusion of financial toxicity in its latest guidance reflects a growing recognition that treatment value includes both clinical outcomes and economic burden. Areas where proton therapy may still offer advantages, such as reirradiation and higher-risk disease, remain under investigation.

The outlook for people with prostate cancer has greatly improved in recent years, with a 10-year survival rate of 98% for all stages combined, according to the American Cancer Society. Recent advances include the FDA approval of the radiopharmaceutical therapy Pluvicto for metastatic prostate cancer, and efforts are under way to develop imaging tests that help plan surgery with greater precision to protect nerves and reduce the risk of incontinence.