Does Massage Spread Cancer?

Does Massage Spread Cancer?

Here we are again with this question, but it is a very important question that should be addressed. This has been prompted by the recent Thinking Practitioner Podcast with Til Lauchau and Whitney Lowe with special guests, Cathy Ryan and Erika Slocum titled ‘New Evidence: Can massage spread cancer?’.

As I am sure you know, historically it was thought that massage could spread cancer, but this was overturned towards the end of last century. It is now commonplace for massage to be available for those living with cancer including hospice and in palliative cancer care. In some hospitals, massage for those living with cancer is also available through the NHS.

At the 2018 Fascia Research Congress (FRC) in Berlin Germany, Prof. Peter Friedl, a clinical researcher investigating the metastasis of cancer, provided a presentation on his research. Here is a link to something similar her presented in 2016. To say that his presentation at the FRC caused a stir is an understatement! Prof. Friedl also offered a short afternoon presentation hosted by Dr Robert Schleip which was standing room only until many people were asked to leave the room due to safety and fire regulations!  I was one of the few who was allowed to stay to listen to the discussion. However, between Prof. Friedl and another FRC presenter Prof. Melody Swartz, there were some differing views about providing soft tissue therapies for those with cancer.

Prof. Friedl showed that cancer can spread through the fascia (interstitium) and he was quite clear that we should not massage cancer tumours. In contrast, Prof. Swartz who research was based on the lymphatic system and cancer suggested that massaging tumours would initiate an immune response and would be beneficial to slowing down the cancer spread. The more lymphatic channels around a tumour, the increased likelihood of tumour metastasis. However, these increased lymphatic channels would communicate with the lymph nodes and become involved in lymph-angiogenesis increasing the immune response. She continued to say that active tumour cells will flow through the channels anyway so soft tissue intervention wouldn’t make that ‘that big of a difference’ but it would make a difference for the immune system to be reactive against the tumour. Food for thought!

Despite these quite bold statements, not much was said or done post the FRC in 2018. So, now what?

In early 2020, we travelled to an Osteopathic conference focusing on fascia in Scheveningen, Netherlands. Prof. Friedl was also presenting at this conference discussing the extracellular matrix as a transport system and we wanted to have another listen to his talk. Prof. Friedl is not a therapist; he does not research the mechanism of therapies, but his career focuses on cancer research. He once again discussed his research implanting a tumour (a fluorescent solid cancer-cell pellet) into a mouse and investigated how these cancer cells move through tissue using a ‘modified dorsal skin-fold chamber model’ which is a small metal device with a window attached to the mouse’s back. He was able to show that the tumour cells move through the tissue by collective invasion sliding between the interfaces (layers) being guided by these pre-existing structures to propagate and spread. To propagate, the flow of cells have a ‘leader’ tumour cell that pushes open the tissue interfaces. There is an equilibrium between the pressure of this leader tumour cell and the tissues that creates reciprocal deformation resulting in the very clear strands of tumour growth perpendicular to the tumour boundaries (pic in my FB post below and in the presentation linked to Prof. Friedl above). He also researched the ‘spaces’ in the interstitium. These spaces are what Neil Theis MD discusses. Dr Theise had previously thought the gaps or holes in the tissues he was looking at in microscopy were tissue artefact; tissue that has been damaged between harvesting, preparation and imaging. However, Dr Theise and the research team he was working with identified these holes, or artefacts, as conduits through the tissue realising the 3D nature of the tissue. Here is their research. Dr Theise had also presented his groups research at the 2018 FRC in Berlin.

It was these conduits that Prof. Friedl was able to identify using a fluorescent tracer to show that they were filled with fluid (proteoglycans including hyaluronic acid and heparin sulphate) and are highways, or transport mechanisms, allowing cells, including tumour cells, to migrate through the tissues. In 2020, he also continued to say that he was very concerned by the comment of ‘another speaker’ at the 2018 FRC because they had two very differing opinions about hands-on therapies and cancer tumours.

Adding further to this debate, at the 2020 Osteopathic conference, Dr. Heike Jäger also a researcher, and not a therapist, discussed mechanotransduction from a macro level to a micro level and electrophysiological changes in cells. Her research investigated cell migration when Piezo ion channels allowed calcium, which regulates lots of cell processes, to flow into the cell. She said that normal migration occurs due to electrophysiologic cell changes. However, cancer cells cause a complete reorganisation of the activation of Piezo channels allowing too much calcium to enter the cancer cell. This calcium overload stimulates fibroblasts to stiffen the ECM that pulls on the cancer cell membrane mechanically activating the Piezo ion channels holding them open. This allows more calcium to enter the cell disrupting integrin sampling causing fibroblasts to further stiffen the ECM. Additionally, these changes also mechanically induce gene expression of the ion channels resulting in more ion channels distributing themselves in the cell membrane ultimately promoting cancer cell proliferation. In her opinion, as Piezo channels are mechanically activated (by pressure), she did not advocate soft tissue therapies (hands-on touch) at all for those living with cancer for at least 5-10 years post remission.

I first posted in FB about this just after the 2020 conference in the Netherlands, link at the bottom of the page.

So, where are we now? Til and Whitney's podcast introduces another recent research paper discussing the metastasis of osteosarcoma, a malignant bone tumour and its relationship with receiving manipulative (massage) therapy. The paper concludes, ‘…there was a higher proportion of metastases in the manipulation group …. the time to metastases was significantly faster in patients with prior manipulation therapy.’ (Karda et al., 2023).

On first look at this study, you automatically think this paper concludes that receiving massage causes metastasis and that the control group did not receive massage and the experimental group did. Really, did the knowingly massage cancer tumour to see what metastasised and what didn't?  No they did not! However, the main focus of the podcast discussion appears to have asked what type of massage was provided and what pressure was used. It was also discussed if an inappropriate pressure was applied that is different to more recent oncology massage training and of course they maintained the stance that we don’t massage the site of tumours.

Let’s just look at this research paper.

Apparently in Indonesia, it is commonplace for people to seek out complementary therapies, including traditional massage, to cure or fix non-specific pain. As a result, many people try massage a number of times before realising that something is really wrong, go to the hospital and, unfortunately end up with a cancer diagnosis. This fact is highlighted in a number of different papers cited from this Karda et al. 2023 paper. This paper also discusses additional research that has identified the potential for ‘micrometastasis due to hypervascularization, which results in poor prognosis’ when tumour sites have been massaged prior to diagnosis. (Miwa et al., 2019)

What’s important here is that the massage therapy was received prior to osteosarcoma diagnosis. This Karda et al. 2023 paper has 2 groups of people who all were diagnosed with osteosarcoma. One group who had received massage prior to diagnosis and one group who hadn’t received massage prior to diagnosis. The group who had received massage prior to diagnosis was also divided into those who had received less than 3 massage treatments prior to diagnosis and those who had 3 or more massage treatments prior to diagnosis. This was to establish if more massage (frequency) resulted in a reduced time to metastasis occurrence.

Those who had received massage prior to diagnosis had:

1. a poorer prognosis,
2. a greater instance of limb amputation,
3. a greater occurrence of pulmonary metastasis and,
4. a reduced 5-year survival rate

compared to the group who had not had massage prior to diagnosis.

In the massage group, the average time from diagnosis to metastasis was 4 months and in the non-massage group was 12 months. However, regardless of how many massages they had, (less than 3 or, 3 or more) there was no statistical difference in the rate of metastasis.

The authors do ask what the mechanism by which massage might cause metastasis. They cite a paper by Diaz et al., 2004 who investigated the spread of benign cells from the breast tissue via lymph to the axillary lymph nodes after breast massage. This study was asking if benign mechanical transport of cancer was possible, i.e. that it is not only by metastasis. While Diaz et al. 2004 do establish that benign cells migrate to the lymph nodes, they conclude that there was not enough evidence to suggest that massage initiated this migration alone. They suggest that it could be possible for cells to have been disturbed from a previous biopsy and breast massage caused these cells to migrate. This 2004 paper then suggests that mechanical loading (massage) can initiate cell migration.

The Karda et al. 2023 paper also references a 2014 study (Wang et al., 2014) who also discusses the metastasis of cancer after manipulative full-body therapy such as massage or Tiuna. Here again though, massage was provided prior to cancer diagnosis. This study shows that those who received massage prior to their diagnosis had increased Matrix metalloproteinases (MMP). MMPs degrade ECM proteins and dysregulate cell functions, proliferation, differentiation, adhesion and migration.

One further paper cited from the Karda et al. 2023 paper is a case report of a 12-year-old male who had received massage and subsequently was diagnosed with osteosarcoma. Tests revealed micro-metastasis eventually leading to lung and liver metastasis (Miwa et al., 2019).

What’s important to take from these studies?

1. Massage on the site of a tumour could cause haemorrhage and dissemination of the tumour (leading to metastasis) – this is why we don’t massage tumours.
2. Massage was performed from a traditional aspect commonly accepted as healing and seems to be a culturally preferential route to allopathic healthcare.
3. Socioeconomic factors in some areas of Asia result in a tendency to use financially acceptable health related care.
4. There is potential for a poorer prognosis because of the delay in cancer diagnosis – more time was spent receiving massage with an aim to alleviate symptoms.
5. If patients were diagnosed earlier, and had not gone via the massage route, prognosis may have been better.
6. It wasn't really about what pressures were used for the massage, it was that massage was the commonly accepted route performed on sites of tumours because they didn't know the tumours existed.
7. As massage appears to be commonly used, perhaps lack of training and knowledge about the signs and symptoms of cancer has had the potential to compound the issue. Training is important!

From reading these papers, it is not the question of what massage was provided and how much pressure was used. It is much more about guiding patients to receive diagnosis and treatment as soon as possible. Also, education is paramount including signs and symptoms to look out for and why massage may be contraindicated. While the studies state that massage can help the symptoms of cancer including promoting relaxation and helping to manage cancer-related pain, they conclude that massaging tumours could result in cancer metastasis leading to poor prognosis.

If I critique this just a little more, it's unfortunate that this Karda et al., 2023 paper cites other papers from 2014 and 2004: these are a bit old. What strikes me is that there still appears to be support of massage for non-specific pain in the general population and education of pathology diagnosis including cancer doesn't appear to be any better than 10-20 years ago. However, if indeed micro-metastasis can occur from massaging a tumour, which supports what both Prof Friedl and Dr. Jäger's research suggests, then this requires further study in the therapeutic field. Also, in acknowledging that there are indeed tissue and cellular changes from mechanical loading, where does this leave the current thinking on manual therapies influence on the ANS as a far more appropriate mechanism of action than mechanical stretching or releasing of tissues? Is this a tissue issue?

Now we have looked at quite a bit of information.

But let’s go back to Prof. Friedl. His research investigated how cancer cells move through tissue. He supported the fact that we should not massage tumour sites. Dr. Heike Jäger suggested that cell dynamics are altered in a cancer environment and influence the mechanical sensitive Piezo ion channels in cell membranes. She did not advocate massaging people with cancer, especially tumour sites. The last studies surrounding the Karda et al. 2023 study all indicate that in the case of osteosarcoma, using massage to resolve non-specific pain and delaying cancer diagnosis, can result in a poor prognosis with the potential to increase metastatic rate if tumour sites are massaged. Only Prof. Melody Swartz concluded that there is a positive influence to be gained by massaging cancer tumours.

Lastly, how much pressure might cause cancer cells to spread? This is what Prof. Friedl showed. In his mouse model with the ‘modified dorsal skin-fold chamber model’ he used a small metal tool and gently pushed down on the tumour and the cancer cells migrated along their tissue highways. This was a tiny amount of pressure. At which point, there is always a resounding ‘ohhhhh’ from the audience. He describes this as like toothpaste being massaged out the tube and that's exactly what it looks like. Just that little bit of pressure caused the cells to move. Is that what we are doing when we massage the tissue?

Points to remember:

1. It’s a mouse model.
2. It’s also an active tumour – we don’t massage tumours.
3. A mouse can’t tell us about their condition.
4. But – we still have to acknowledge that we might not know where the tumour boundaries are, and we might not even know that there are tumours.
5. Acknowledge that we don’t know everything.
6. Training is important.

My take home message. Don't massage tumour sites (we don't anyway). In not throwing out Prof. Swartz comments about massaging tumour sites as this would help immune system regulation, what if we put this a different way? Massage can make a difference by means of downregualtion of the ANS which can reduce the influence of the neuro-immune-endocrine response ultimately helping people living with cancer manage their cancer related pain. That is, pleasant touch, avoiding known tumour sites, activates the social touch fibres (C-tactile afferents). This sensation goes to the limbic system promoting a feeling of wellbeing and relaxation. As a result, there is a reduction of 'inflammatory soup' and improved organism regulation by the HPA and SAM axes. So, I hypothesis that indeed there is potential for immune regulation being more reactive against the tumour taken from this point of view - but (obviously) this needs further study and a whole lot more typing!

So, where do we go from here? What do you think?

Diaz, N. M., Cox, C. E., Ebert, M., Clark, J. D., Vrcel, V., Stowell, N., Sharma, A., Jakub, J. W., Cantor, A., Centeno, B. A., Dupont, E., Muro-Cacho, C., & Nicosia, S. (2004). Benign Mechanical Transport of Breast Epithelial Cells to Sentinel Lymph Nodes. Am J Surg Pathol , 28(12), 1641–1645.

Karda, I. W. A. M., Wan Ismail, W. F., & Kamal, A. F. (2023). Massage manipulation and progression of osteosarcoma, does it really correlate: a combination of prospective and retrospective cohort study. Scientific Reports 2023 13:1, 13(1), 1–6. https://doi.org/10.1038/s41598-023-45808-7

Miwa, S., Kamei, M., Yoshida, S., Yamada, S., Aiba, H., Tsuchiya, H., & Otsuka, T. (2019). Local dissemination of osteosarcoma observed after massage therapy: A case report. BMC Cancer, 19(1), 1–6. https://doi.org/10.1186/S12885-019-6246-4/FIGURES/9

Wang, J. Y., Wu, P. K., Chen, P. C. H., Yen, C. C., Hung, G. Y., Chen, G. F., Hung, S. C., Tsai, S. F., Liu, C. L., Chen, T. H., & Chen, W. M. (2014). Manipulation therapy prior to diagnosis induced primary osteosarcoma metastasis - From clinical to basic research. PLoS ONE, 9(5). https://doi.org/10.1371/journal.pone.0096571