Tag: anti-hormone drugs

Categories : CancerTags :

Hormone Therapy of Little Benefit with Radiotherapy after Prostate Surgery

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Findings could help patients avoid side significant effects and improve quality of life

Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

A new study led by UCLA Health investigators suggests that adding hormone therapy to post-operative radiotherapy may provide little survival benefit for most men with prostate cancer, especially for those with very low PSA levels before treatment. 

The researchers found that for men with low PSA levels prior to radiotherapy, adding hormone therapy, whether short-term or long-term, did not improve overall survival. Men with higher PSA levels before radiation may see modest improvements in survival and metastasis-free survival, suggesting hormone therapy may be beneficial primarily for this higher-risk group.

The results were published in The Lancet and presented by Dr Amar Kishan, professor and executive vice chair of radiation oncology at the David Geffen School of Medicine at UCLA, during the plenary session of the American Society of Clinical Oncology Genitourinary Cancers Symposium in San Francisco. 

“Hormone therapy, which impacts the ability of testosterone to stimulate prostate cancer growth and repair, has been shown to improve outcomes when combined with radiotherapy in men whose prostates are still intact. However, whether it has a similar benefit for men receiving radiotherapy after prior surgery has remained unclear,” said Kishan, first author of the study and co-director of the cancer molecular imaging, nanotechnology and theranostics program at the UCLA Health Jonsson Comprehensive Cancer Center. “At the same time, hormone therapy carries significant side effects, including severe fatigue, hot flashes, sexual dysfunction, weight gain, bone loss and metabolic changes that can increase cardiovascular risk. Our findings show that for most men with detectable but low PSA levels (<0.5 ng/mL), after surgery to remove the prostate, post-operative radiotherapy is highly effective on its own. By safely omitting hormone therapy in these patients, we can potentially spare them months of treatment that may substantially affect their quality of life without extending survival.”

To better understand the impact of hormone therapy in this setting, the researchers conducted a large-scale, individual patient-level meta-analysis through the MARCAP Consortium, an international collaboration co-led by Kishan that is designed to evaluate long-term outcomes across randomized clinical trials.

The team analysed data from 6057 men enrolled in six randomised trials comparing post-operative radiotherapy alone to radiotherapy combined with either short-term (4-6 months) or long-term (24 months) hormone therapy. By pooling individual patient data rather than relying on summary trial results, investigators were able to examine outcomes in greater detail, including how pre-radiation PSA levels influenced treatment benefit.

Patients were followed for a median of nine years, allowing researchers to assess long-term overall survival, metastasis-free survival and recurrence outcomes. The analysis also enabled direct comparisons between short-term and long-term hormone therapy to determine whether extending treatment duration improved outcomes.

The researchers found that overall, 83.6% of men who received post-operative radiotherapy alone were alive after 10 years, compared with 84.3% for those who received post-operative radiotherapy plus hormone therapy.

Researchers found that pre-radiotherapy PSA levels, a measure of prostate-specific antigen in the blood after prostatectomy, played a crucial role. Men with low PSA levels before radiotherapy (≤0.5 ng/mL) saw no benefit from hormone therapy. In contrast, men with higher PSA levels showed modest improvements in survival, suggesting that hormone therapy may only be worthwhile for those with elevated PSA. 

The study also examined the duration of hormone therapy. Short-term therapy did not improve overall survival, though it slightly reduced the risk of cancer spreading. Long-term therapy showed a small survival benefit, particularly for men with higher PSA levels after prostatectomy. However, the team’s statistical analysis demonstrated that extending short-term therapy to long-term therapy did not further improve survival, although it did modestly lower the risk of metastasis.

“Our goal is always to treat the cancer while minimizing harm,” said Kishan. “This study helps us move toward more personalised care for men with prostate cancer. By better identifying who truly benefits from hormone therapy, we can make treatment smarter, reduce unnecessary interventions and focus on improving patients’ overall well-being.”

Building on those findings, ongoing research is working to further refine that approach. Trials such as the BALANCE Trial aim to pinpoint biomarkers that can identify which men are most likely to benefit from hormone therapy after surgery, helping tailor treatment decisions even more precisely.

Source: UCLA Health

Categories : CancerTags :

Matching Drugs to DNA of Metastatic Prostate Cancer Boosts Survival

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Credit: Darryl Leja National Human Genome Research Institute National Institutes Of Health

Men with metastatic castration-resistant prostate cancer should be treated primarily with second-generation hormone drugs, which offer better treatment response and longer life expectancy than chemotherapy. But the effect depends on which mutations the patient’s tumour carries. This is shown by results from the ProBio study, led by researchers at Karolinska Institutet in Sweden. The findings are published in Nature Medicine.

Every year, around 2500 men in Sweden are diagnosed with metastatic prostate cancer. Initially, all are treated with testosterone blockade to prevent testosterone from activating the androgen receptor, the gene that mainly fuels the growth of cancer cells. Over time, the cancer cells develop resistance and become so-called castration-resistant. This requires the use of new drugs – usually chemotherapy or second-generation hormone drugs (abiraterone/enzalutamide) that inhibit the androgen receptor. These are called Androgen Receptor Pathway inhibitors, or ARPi. Although these drugs have been available for over a decade, there is no direct comparison from a randomised trial until now.

Personalised treatment

“For the first time, we have compared these treatments with each other and also analysed the DNA of the cancer cells to find out which drug that works best for different individuals,” says Johan Lindberg, senior researcher at the Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet.

The bloodstream contains so-called cell-free DNA from cells that have died, something that happens all the time in healthy individuals and is perfectly normal. In patients with cancer, a fraction of the cell-free DNA originates from the cancer cells and is called circulating tumour DNA (ctDNA). By analysing ctDNA, it is possible to see what changes, or mutations, are present in a person’s tumour. The ProBio study aims to use knowledge of the tumour’s genetic signature to provide the best treatment. The idea is to be able to identify patients whose tumours are particularly sensitive or resistant to certain treatments through ongoing analyses.

“It creates a self-learning system to continuously improve treatment for men with metastatic prostate cancer,” says Martin Eklund, Professor of Epidemiology at the same department. “We are also gathering knowledge about which regions of the genome are important in prostate cancer.”

Longer life expectancy

The current sub-study included 193 patients with metastatic castration-resistant prostate cancer. They were randomly chosen to receive either chemotherapy or ARPi, which was compared to a control group where the doctor decided on the best treatment. The ARPi group responded the longest to treatment (a median of 11.1 months compared with 6.9 for chemotherapy and 7.4 for the control group). Survival for the ARPi group was also significantly longer – a median of 38.7 months compared with 21.7 months and 21.8 months respectively.

The effectiveness of ARPi varied depending on the patient’s genetic profile. For example, there was no significant difference between the treatments in the short term in patients whose tumours had mutations in the p53 gene, which occurs in around 45% of men with metastatic prostate cancer. However, data from the study suggest that also this group may have better survival if they receive ARPi rather than chemotherapy.

Source: Karolinska Institutet