Cancer screening faces renewed scrutiny while implantable immunotherapy takes a significant clinical step forward.
Screening processes in prostate cancer and colorectal cancer are being called into question, while the first-in-human study of implantable immunotherapy for ovarian cancer has yielded positive early results.
PSA screening still controversial
A recent update to the Cochrane review of PSA testing concluded that while PSA screening may slightly reduce prostate cancer-specific mortality, its effect on overall survival remains unclear.
Despite increased cancer detection, screening did not clearly or consistently reduce advanced disease, and instead introduced the risk of overdiagnosis.
The update brought together data from six randomised controlled trials involving nearly 790,000 men aged between 45 and 80 years across Europe and North America, incorporating two new large studies and longer-term follow-up data from the trials included in the 2013 review.
Five of the trials comparing PSA-based screening, sometimes combined with digital rectal examination, against usual care where no organised screening was offered. Three major studies – the CAP trial in the United Kingdom, the PLCO trial in the United States, and the ERSPC trial conducted across multiple European countries – accounted for the vast majority of participants.
Screening was associated with an approximately 13% relative reduction in prostate cancer mortality, translating to roughly two fewer deaths per 1000 men screened. However, the effect on overall mortality showed no significant difference between screened and unscreened groups.
In terms of harms, the evidence suggested that PSA screening does not clearly increase or decrease serious adverse events such as death related to biopsy or treatment, although the certainty of this finding is low due to limited reporting. Similarly, quality of life appeared largely unchanged between screened and unscreened groups, with minimal differences observed on standard health-related quality-of-life measures.
One consistent finding was that PSA screening increases the number of prostate cancer diagnoses, particularly detecting more early-stage, localised cancers. It didn’t substantially reduce the incidence of advanced-stage disease overall, although there was some evidence suggesting a modest reduction in metastatic cancer diagnoses.
One study examined a newer screening approach combining PSA testing with kallikrein-based blood markers and magnetic resonance imaging, although only early results are currently available.
These findings suggest it may increase the detection of prostate cancer compared with no screening, including both localised and advanced disease, but the current data are insufficient to determine whether it reduces deaths or improves long-term outcomes.
Review authors noted that while these newer approaches are promising, it’s too early to draw any firm conclusions about their potential clinical benefit.
Immunotherapy implants reach human trials
A first-in-human study has shown early promise for a novel implantable immunotherapy designed to treat advanced ovarian cancer by delivering immune-stimulating proteins directly to the site of disease.
The technique, developed by researchers at Rice University in collaboration with The University of Texas MD Anderson Cancer Center, uses encapsulated, engineered cells that function as “cytokine factories.”
Once implanted into the abdominal cavity, the device continuously produces interleukin-2 (IL-2) locally for around one week. IL-2, a cytokine known for activating immune responses against cancer, has had somewhat limited clinical use given the risks of severe toxicity and a very
The investigational therapy, known as AVB-001, was evaluated in a Phase 1 dose-escalation trial involving 14 patients with platinum-resistant high-grade serous ovarian cancer who received a single laparoscopic intraperitoneal implantation of the device.
According to the researchers, the goal was to concentrate immune activation within the tumour environment while minimising the systemic side effects that have long restricted IL-2 therapy.
“Traditional IL-2 therapy has shown potent antitumor activity, but its clinical use has been limited by severe side effects and delivery challenges,” said Dr Omid Veiseh, a professor of bioengineering at Rice University and a senior author of the study.
IL-2 has a very short half-life when administered systemically but the implantable system, researchers noted, enables sustained local exposure of the cytokine directly where tumours are present.Â
Related
Immune profiling showed increased activity in key antitumour cells, including CD8+ T cells and natural killer cells, along with elevated inflammatory signalling. Notably, there was no increase in regulatory T cells, which can suppress immune responses and often limit the effectiveness of conventional IL-2 treatment. These findings suggest that localised delivery may help overcome one of the major drawbacks of systemic cytokine therapy, authors noted.
The study also observed increased expression of CTLA-4, an immune checkpoint protein, raising the possibility that combining this therapy with checkpoint inhibitors could enhance anti-cancer effects. Researchers described this as a potential avenue for future combination strategies aimed at amplifying immune responses.
While still early results, the treatment was generally well tolerated, with no dose-limiting toxicities or treatment-related deaths observed and no maximum tolerated dose reached during the trial. Importantly, several patients experienced disease stabilisation, and about half showed periods where disease progression was temporarily halted.
“These patients have very limited treatment options, so even achieving disease stability is encouraging at this stage,” said Dr Shannon Westin, a gynaecologic oncologist at UT MD Anderson and co-lead investigator of the trial.
The next stage of development will focus on optimising dosing schedules and exploring combination therapies, particularly with immune checkpoint inhibitors.
Colonoscopy reduces colorectal cancer incidence but not mortality
A large international trial, published in The Lancet, has found that a single screening colonoscopy reduces the risk of developing colorectal cancer but has not yet demonstrated a significant reduction in deaths from the disease after 13 years of follow-up.
The updated findings come from a randomised controlled trial involving 84,583 adults aged 55 to 64 years from Norway, Poland, and Sweden. Participants were randomly assigned to either receive an invitation for colonoscopy screening or receive no screening.
Over 13 years, colorectal cancer was diagnosed in 1.46% of people offered screening, compared with 1.80% of those in the control group. This equates to a 19% relative reduction in cancer incidence among those invited for screening. The reduction was more pronounced among participants who actually underwent colonoscopy.
The benefit was largely driven by fewer cancers occurring in the distal colon and rectum, while the incidence of cancers arising in the proximal colon was similar between the two groups. The reduction in colorectal cancer risk was also greater in men than in women.
Despite the lower incidence of cancer, researchers did not observe a statistically significant reduction in colorectal cancer mortality. Deaths from colorectal cancer occurred in 0.41% of participants in the screening group and 0.47% of those who were not screened.
The investigators noted that colorectal cancer mortality in the control group was substantially lower than anticipated when the trial was designed, which may have reduced the study’s ability to detect a mortality benefit. Improvements in cancer treatment and increased awareness of colorectal cancer over time may also have contributed to lower-than-expected death rates.
The findings build on the study’s previously reported 10-year results and suggest that the protective effect of colonoscopy screening against cancer development persists over longer follow-up. However, whether this translates into a meaningful reduction in deaths remains uncertain.
The trial is ongoing, and researchers say additional follow-up will be important to determine whether a mortality benefit emerges over time.
