After curative-intent treatment, prostate cancer recurrence is still an unmet need

Paul Peter Tak, MD, PhD, FMedSci, is a physician-scientist and former Professor of Medicine and Chair of Clinical Immunology and Rheumatology at Amsterdam University Medical Center. He previously served as Chief Immunology Officer and Global Development Leader at GSK and is an elected Fellow of the UK Academy of Medical Sciences.

___

A man diagnosed with localized prostate cancer today can benefit from advances that were not available 2 decades ago. Multiparametric MRI can improve decisions about whether and where to biopsy. Molecular tests can add information about risk. PSMA-PET imaging can reveal disease that conventional scans may miss. Active surveillance allows many men with low-risk cancer to avoid or delay treatment they may never need.

These advances matter. So do improvements in surgery and radiotherapy. But for a patient who chooses radical treatment with curative intent, progress should be judged by a simple, human question: Can I live the rest of my life without evidence that the cancer has returned? Too often, the answer is still uncertain.

What do patients expect from curative treatment?

Patients accept surgery or radiotherapy because they want the cancer eradicated. They want to avoid symptoms caused by cancer growing again in the prostate or spreading elsewhere. They want to avoid, or at least delay, further anticancer treatment. And they want to protect the quality of the years ahead, for themselves and for the people who share their lives.

A rising prostate-specific antigen, or PSA, after treatment may be the first sign that cancer has returned. It can arrive before symptoms, but it is not merely a laboratory result. It can trigger repeat testing, new scans, difficult decisions, and the recurring anxiety of waiting for the next number. Depending on a man's original risk and treatment, recurrence is not rare; published reviews describe substantial rates of biochemical recurrence after definitive therapy.

Recurrence changes more than a test result

When prostate cancer returns, care may include additional radiation, surgery in selected cases, or systemic treatment. One common option is androgen deprivation therapy, or ADT, which lowers or blocks testosterone and is sometimes called medical or chemical castration.

ADT can control prostate cancer and may be clinically necessary, but its effects can be far-reaching: hot flashes, fatigue, loss of muscle and bone strength, metabolic changes, changes in mood or cognition, and loss of libido and sexual function. These consequences affect the patient, but they can also reshape intimacy, daily routines, and emotional well-being for partners. The point is not to discourage appropriate treatment. It is to recognize that delaying or avoiding salvage therapy, when safely possible, is itself a meaningful outcome.

Patients therefore care about more than overall survival. They care about living without detectable cancer, avoiding local and metastatic progression, remaining free from additional therapy, and preserving physical, sexual, and emotional health. Our clinical trials and treatment goals should reflect that full picture.

Better detection is not the same as better prevention

Medicine has become much better at finding prostate cancer and identifying who is most likely to relapse. That knowledge supports better conversations and more tailored care. Yet predicting recurrence is not the same as preventing it.

This distinction matters. Some gaps in cancer care are implementation gaps: proven interventions do not consistently reach the people who need them. Those failures demand better access, earlier diagnosis, shared decision-making, and equitable delivery. But even if every man received excellent care, some cancers treated with curative intent would still return. That is a therapeutic gap.

We should be careful not to diminish genuine progress. Modern radiotherapy is more precise. Surgical care has improved. Treatment is increasingly matched to risk. At the same time, we should be equally careful not to confuse refinement with completion. The continued burden of recurrence tells us that the work is unfinished.

What should change next?

First, research in localized prostate cancer should prioritize outcomes that patients immediately recognize as valuable: freedom from evidence of recurrence, metastasis, and additional therapy, together with quality of life. Overall survival remains essential, but it should not be the only measure that counts.

Second, we need rigorously validated earlier measures that can show whether curative-intent treatment has truly controlled or eradicated disease. Prostate cancer can unfold over many years. Without credible earlier readouts, trials may become so long and difficult that important questions are never asked.

Third, patients and partners should have a stronger voice in defining benefit. Continence, sexual health, energy, cognition, bone health, emotional well-being, and freedom from treatment are not secondary concerns. They are part of the outcome.

Finally, studies must include the people most affected by the disease. Black men continue to bear a disproportionate burden from prostate cancer, yet they have often been underrepresented in research. Better science requires representative participation.

The goal is to be finished with cancer

For men who choose radical treatment, success is not simply living longer after a recurrence. The aspiration is to live without evidence of recurrence, without symptoms from progressive disease, without metastases, and without years of additional treatment and its toxicities.

During Prostate Cancer Awareness Month, we should celebrate how far diagnosis and treatment have come, but we should also listen closely to what patients are asking from therapy with curative intent. They do not only want us to find cancer earlier or predict its return more accurately. They want us to prevent it from coming back.

__

Editor’s note: Tak is President and Chief Executive Officer of Candel Therapeutics and holds equity in the company. He chairs the board of Citryll, serves as a board director of Levicept and Sitryx, which he co-founded, and is a trustee of the Kennedy Trust for Rheumatology Research.