When prostate cancer is aggressive: How 65-year-old recovers with combination drug therapy that reduces mortality risk by 40%

Thiscombination therapy has been effective according to a Phase 3 clinical trial for high-risk, recurring cancer. “Prostate cancer is the third most common cancer in men. The best part is that this combination therapy is readily available in the country, which can help in better survival outcomes,” says Dr Amit Joshi, professor, Department of Medical Oncology, Tata Memorial Centre’s Advanced Centre for Treatment Research and Education in Cancer (ACTREC) unit, who treated Patil. Which is why he advocates indication-driven screening, so that even the most aggressive form can be managed in time.

The combination of leuprolide and enzalutamide cuts prostate cancer risk by attacking it on two fronts: leuprolide suppresses the production of the male hormone testosterone, while enzalutamide blocks the remaining testosterone from fuelling cancer cells. This dual approach starves the cancer cells, which rely on testosterone to grow, thus slowing growth, potentially shrinking tumors, and delaying spread. “Prostate cancer develops without noticeable symptoms in its early stages but screening can help detect it early, when it is most treatable,” says Dr Kamlesh Bokil, a Pune-based surgical oncologist.

Cancer returns despite early therapy

A digital rectal examination revealed a lump on the right side of his prostate. Further image testing with an MRI showed a suspicious lesion and a biopsy confirmed the diagnosis of prostate cancer. Luckily, a PET scan suggested that the growth had been confined to the prostate gland only. But it was high risk and aggressive (he had high PSA and had a high Gleason score, which measures the volume of abnormal cells). That’s why apart from removal of the prostate gland, Patil’s doctors removed lymph nodes from the pelvic area. “Since his was a high risk case, we also administered radiotherapy based on his pathology report to eliminate microscopic malignant cells that might have remained after the surgery,” says Dr Joshi.

His PSA level dropped to 0.4 ng/ml after radiotherapy. He was kept under observation with PSA tests every three months. However, about a year after surgery and radiation, his PSA levels started rising again. In eight months, his PSA increased to 2.8 ng/ml, indicating that the cancer might have returned. This is called biochemical recurrence, the first sign of cancer possibly returning and can occur even when there are no physical symptoms. This indicated that some cancer cells had survived the first cycle of Patil’s treatment. Patients who have biochemical recurrence, with their PSA levels doubling in less than nine months, are at a high risk of metastasis, or an aggressive spread. However, a repeat scan now has not shown any visible disease.

How combination therapy works

In January this year, doctors gave him leuprolide injections (22.5 mg every three months) and enzalutamide tablets (160 mg daily), following the EMBARK protocol. His PSA levels began to drop steadily, reaching 0.05 ng/mL after three months and became undetectable by six months. After 37 weeks of treatment, in October 2025, his doctors stopped the medication. “Now he continues with regular PSA monitoring every three months,” Dr Joshi says.

What a new trial says about combination therapy

Patil’s progress after the drug combination therapy is in tune with the findings of a phase III EMBARK trial (published in the New England Journal of Medicine last week) that showed overall survival was significantly longer with the leuprolide-enzalutamide combination. Their combined use improved survival rates in patients with locally advanced prostate cancer and reduced the risk of death by over 40 per cent. “In most cases, PSA levels remain stable, indicating good disease control. However, in a small number of patients, the cancer can behave aggressively. Therefore, it is important to identify those patients at higher risk after surgery and radiation,” says Dr Joshi.

In the EMBARK trial, close to 1,000 patients with prostate cancer (from across 17 countries), who had high-risk biochemical recurrence, were randomly assigned to receive enzalutamide plus leuprolide (the combination group), leuprolide-only or enzalutamide monotherapy (the monotherapy group) in a 1:1:1 ratio. The survival analysis demonstrated that the enzalutamide combination therapy was associated with a 40.3 per cent lower rate of deaths, compared with leuprolide alone (eight-year survival at 78.9 per cent versus 69.5 per cent).

Why screening is important

As per the American Cancer Society, screening should be done for asymptomatic men at age 50. PSA and digital rectal examination can be done after consultations with your doctor on pros and cons of PSA testing. For those with risk factors such as family history, screening should be done at age 45. Those with an even higher risk (those with more than one first-degree relative who had prostate cancer at an early age or a known genetic mutation like BRCA 1 and 2 with history of breast or ovarian cancer), should get screened at 40. Last year, the International Agency for Research on Cancer projections had said that prostate cancer incidence in India will double to about 71,000 new cases per year by 2040.

(Name changed to protect privacy)