Sure, poking through a tumour with a sharp biopsy needle can dislodge cancer cells from it. But what does that mean for a cancer patient? Will dislodged CTCs have an impact on treatment outcomes? Where do those cells go, and what happens to them? Can those cells start new cancer colonies (metastases) elsewhere in the body?
“The clinical significance of [prostate tumour] seeding has not been clearly defined, and there are no guidelines for its prevention or management,” stated another 2014 review of Dimitrios Volanis, MD, PhD, a consultant urologist at the Royal Free London NHS Foundation Trust. “Clinicians are, therefore, often unable to provide evidence-based counselling about the ‘real’ risk of seeding and its impact on prognosis. Indeed, tumour seeding is not mentioned or cited as a risk of biopsy in the European Association of Urology (EAU), American Urology Association (AUA), or UK National Institute for Health and Care Excellence (NICE) guidelines.”
While health authorities have not provided definitive answers on what might happen after prostate cancer biopsy, there are at least five plausible scenarios based on the existing literature:
It is only in a 2020 study that researchers first tracked a group of prostate cancer patients, of whom 29% (i.e., 22 out of 75) had increased CTCs after biopsy, for the next 3.5 years. Results found that 45% (10 out of 22) of those with increased CTCs experienced cancer progression. This number was only 15% (8 out of 52) in prostate cancer patients without CTCs. Importantly, results remain significant even after adjusting for potential confounding variables, such as age, cancer severity, and therapy received. “Because of the number of CTCs before biopsy alone was not correlated with progression of disease, these data supported that the additional mechanical release of prostate cells into the circulation of participants influenced prognosis,” the study authors wrote. This study “should ring a bell for the community, as it provides important evidence that traumatic biopsies are not neutral on disease progression,” cautioned Nicola Aceto, a professor of oncology.
While the 2020 study examined cancer progression, the research on biopsy and recurrence in prostate cancer is limited. To date, there are only case reports. Three cases of cancer recurrences in the bladder wall and perineum struck prostate cancer patients a few years after brachytherapy. This treatment involves needle insertion into the tumour to deliver radiation to kill cancer cells. One incident of tumour seeding into the rectal wall has also been reported recently following a transrectal prostate biopsy. Notably, there is one published case of perineal cancer recurrence 14 years after a transperineal biopsy in a prostate cancer patient. Thorough analyses of the patient’s blood and cancer profiles, the authors wrote, “suggests that the patient would have remained free of disease if the perineal needle tract seeding had not occurred.” However, case studies are just single incidences, which should not be generalized to a broader population.
Since research on biopsy and prostate cancer recurrence is scarce, we can infer insights from other cancers. A 2020 paper analyzed hospital data from 1,047 patients with non-small cell lung cancer, of which 191 patients (18%) faced cancer recurrence after treatment. The researchers found that 20% of this group of 191 patients underwent an imaging-guided biopsy, whereas only 3% in the control (no cancer recurrence) group had the biopsy. That is nearly a seven-times increased risk of cancer recurrence in the biopsy group. Notably, results were adjusted for possible confounding variables, such as age, sex, treatment, and cancer severity. A similar situation applies to colon, breast, and bone cancers, for which biopsies were strongly suspected as the culprit for recurrence.
However, biopsies may be safer for other types of cancers. One 2015 study looked at clinical data of 2,034 patients with pancreatic cancer, of which 498 (24%) underwent ultrasound-guided needle biopsy. After adjusting for con-founders, results revealed lower deaths from pancreatic cancer in the biopsy than control (no biopsy) group – i.e., 50% versus 64% deaths – in a follow-up period of about 21 months. Similarly, in skin cancer, needle biopsies are not associated with any risks of cancer recurrence, concluded a 2016 research review.
All in all, whether biopsy would affect patients’ health outcomes depends on the type of cancer. In prostate cancer, at least we cannot deny that dislodged cancer cells from the tumour into the needle track or bloodstream can happen following biopsy. While tumour seeding into the needle track is rare at 1-2%, biopsy-induced increase in CTCs is much more common, affecting 20-30% of prostate cancer patients. An even more common complication of biopsy is the dislodging of prostate cells (i.e., PSA positive prostate cells or epithelial cell fragments) into the bloodstream, reaching 100% occurrence following biopsy.
As CTCs (and prostate cells) may contribute to cancer progression and recurrence, it could explain why about half of prostate cancer patients suffer cancer recurrence years after surgery and require additional therapies (see section 1: Hypothesis).