For men aged 50-69 years who underwent a one-time prostate-specific antigen (PSA) screening for prostate cancer, a lower prostate cancer-specific mortality was observed after 15 years of follow-up, but the reduction was only slight. Could this be due to the dissemination of cancer cells through prostate biopsies?

The Cluster Randomised Trial of PSA Testing for Prostate Cancer involved more than 410,000 men aged 50-69 years from 573 primary care practices in the UK. Around 190,000 underwent a one-time PSA test between 2002 and 2009, while a control group of 220,000 men did not undergo screening.

After 10 years of follow-up, no significant reduction in prostate cancer-specific mortality was observed. However, a secondary analysis conducted after 15 years revealed a significant difference. Prostate cancer-specific mortality was 0.69% in the intervention group compared with 0.78% in the control group, representing a statistically significant reduction of 0.09% in favour of screening.

Prostate cancer was diagnosed at earlier stages in the screening group (more patients with a Gleason score of 6 or below and with a localised tumour at stage T1/T2), making the slight reduction in mortality somewhat disappointing. According to physicians Mark Goldstein, from Paoli in Pennsylvania, and Luca Mascitelli, from Porcia, Italy, this could be because biopsies performed in response to elevated PSA levels may actually promote the spread of cancer cells. A similar phenomenon is observed in women with early-stage breast cancer, where mortality increases if too much time elapses between the diagnostic biopsy and the definitive surgery.

Needle Biopsy May Seed Tumour Cells

Injury to tumour tissue and its surroundings caused by a biopsy needle can activate macrophages, which promote angiogenesis and tumour cell dissemination. Additionally, the biopsy creates an inflammatory environment with an immunosuppressive microenvironment, potentially allowing the tumour to evade immune detection. It’s important to note that significantly more tissue samples are taken during a prostate biopsy than for a breast cancer diagnosis. Moreover, the active surveillance therapy option often requires repeated biopsies.

Circulating Cancer Cells Detectable After Biopsy

Immediately after a needle biopsy of the prostate, circulating prostate cancer cells can be detected, and the level of increase correlates with shorter progression-free survival. A study of 569 patients with prostate cancer revealed that 70% had disseminated tumour cells in the bone marrow even before undergoing radical prostatectomy. This finding persisted in 57% of the affected patients 20 months after prostatectomy, and it was associated with a nearly sevenfold increase in the risk of recurrence.

According to the authors, future prospective studies should investigate whether non-invasive methods for diagnosing prostate cancer, such as liquid biopsies, genomic testing, or MRI imaging, could improve mortality outcomes.

Reference

Prostate-Specific Antigen Screening and 15-Year Prostate Cancer Mortality: A Secondary Analysis of the CAP Randomized Clinical Trial. JAMA. 2024 May 7;331(17):1460-1470. doi: 10.1001/jama.2024.4011.