In my career, one of the things I have found that has evolved tremendously, is the approach to the care of prostate cancer. The disease used to be simply diagnosed and treated. However, now there is much more attention to its aggressiveness, chances of recurrence, and most importantly, ways of controlling the disease without negatively impacting the quality of a person’s life.
This progress is especially important in the case of intermediate and high-risk localised prostate cancer, when surgery and radiation therapy have proven to be effective treatments. Hormone therapy is used in certain patients depending on their risk factors. Nevertheless, recurrence is still an issue in some cases, after treatment aimed at curing the disease.
This is why the rising interest in immunotherapy for prostate cancer attracts my attention. A recent Phase 3, double-blind clinical trial, published in The Lancet, has added to this conversation by examining whether an immune-based approach can enhance the effects of established treatment, radiotherapy, in men with localised, high-risk prostate cancer.
Harnessing the immune system
Treatment through immunotherapy has changed the scenario in a variety of cancers, and yet, it has proven to be difficult when it comes to treating prostate cancer. Traditional immune-checkpoint inhibitors, for example, cannot be used to treat localised prostate cancer.
The therapy being used in this latest Phase 3 clinical trial, however, differs from traditional therapies. Aglatimagene besadenovec is an innovative viral immunotherapy that works by delivering the therapy directly to the site of the tumour. It works by killing tumour cells and stimulating the body’s immune response against the cancerous cells.
From a clinician’s point of view, this is an intriguing direction since it goes beyond treatment of the tumor via just one pathway. Radiation can be used to control the local growth of the tumour, hormones can address the dependence of the disease on androgens, while the immune system can add yet another layer to the treatment.
A crucial point to remember here, though, is that this is what the immune system can potentially do -- it is not yet a guaranteed outcome. Oncology is a field where an interesting mechanism is just the starting point; one has to wait for more research and trials to help establish the outcome, which is what really counts.
Promising findings
Benefit in terms of disease-free survival was achieved by means of the combination strategy. Another exploratory analysis showed that 80% of patients treated with the experimental therapy were negative for tumour cells in their prostate biopsies after two years, while only 63% of the control group achieved this outcome.
While these results appear promising, it is important to note that they should not be overstated. Specifically, the prostate biopsy was an exploratory analysis for an evaluable subgroup of patients and did not represent the primary endpoint of the trial. Likewise, other outcomes mentioned in the results of the study will need further follow-up and evaluation.
This is crucial for the patient. An encouraging outcome does not guarantee that a new treatment will replace an already existing one.
Bringing immunotherapy in early
Immunotherapy for cancer is mainly used in the case of advanced and metastatic cancer. What I liked about this study is that one can see how immune therapy works at the early stages of cancer when it is localised and treatment aims at curing.
The issue with treating cancer is that despite the absence of any visible tumours in scans, there may still be a trace of the disease left. Could activation of the immune system early help eliminate those cells? This would seem like a good direction for future research.
What patients should know
For now, I think of these results as positive signs rather than a revolution in the established management of prostate cancer.
Individualised decision-making should remain a key component of treatment with attention paid to factors as PSA values, Gleason score, imaging studies, risk group, age, general condition of the patient and his personal preferences. Surgery, radiotherapy and hormonal therapy are essential, and an individual treatment modality varies from case to case.
It’s important to understand that there is continuous progress being made in prostate cancer treatment. Doctors and scientists are beginning to think about how we can combine different treatment methods rather than using only one.
If we will learn in future how to predict who can benefit from immunotherapy, how stable this effect is and if it leads to improved prognosis in the end, then such treatment might become a crucial step in localised prostate cancer treatment.
That is where, for me, the true promise exists, not in replacing something that works but in figuring out how to make it work even better for the patient.
(Dr. Ashwin Giridhar is senior consultant & lead - urology & uro-oncology, HCG Cancer Hospitals, Hebbal, Bengaluru. drashwingiridhar@gmail.com)