Before I commence, I wish to make a disclaimer: this article is based on my opinions and reflections regarding a case I have personally witnessed. Due to the sensitive nature of the disease and the fact that patient consent cannot be sought (reasons of such are to be proffered later), I will remove all possible strands of identification of the patient. Also, I approach this article in a general manner, focusing only on aspects which are material to the points I wish to express. As far as possible, I adhere to the pathophysiological mechanisms of the diseases recorded here, in avoidance of any undue identification.
I was rather shocked when I first saw Tim*. He was a 70-year old, malaise man lying on the furthermost bed in the oncology ward. I've always hated the oncology ward - stuffy, cramped and dimly lit. Not to mention that a bumblebee was ten times more likely to be chastised by the more fearsome consultants in the locality. But then, I saw Tim and my eyes started to well. He was one of the terminal patients, meaning that the cancer was so advanced that his death was imminent (for sceptics claiming that we all die someday, I express this in more precise medical terms: the 1-year survival rate for his condition is below 5%). He said to me that the most pressing problem was his pain. 'Pain in where?' 'The pain in the head.' Off the answer came. He had been suffering from serious headaches lately and had gross motor deficits (could not move well). I checked his records and saw that he was diagnosed prostate cancer. There is a chance that the cancer could have spread to the brain, leading to a mass effect. This is always a concern since the larger the mass, the greater the risk for it to compress the cerebrum, leading to brain herniation. The cerebrum sits on very crucial brain structures. They are responsible for heartbeat, breathing and so forth. Therefore, such a shift can lead to compression of these structures, where death can ensue. I asked him whether he experienced pain anywhere else. 'Yes, my back and my chest.' This strikes me as slightly weird. Pain over the back and chest may suggest bone metastases of a cancer - the weakening of the bone through lysis. This also increases the risk of fracture. Many cancers spread in this way, such as breast cancer and liver cancer. [1, 2] Prostate cancer is special in the respect of activating osteoblasts, i.e. the cells responsible for bone growth, thus leading to the formation of large bone masses.
He recently also experienced problems in sensation over the hands. The nerves might be affected. This can be explained by chemotherapy-induced peripheral neuropathy, which refers to the gradual damage of the peripheral nerves by these chemotherapy drugs, toxic to the extent that they inhibit cell growth and division. [3]
I started doing the basic checks to see if Tim was doing well. I did a neurological exam and assessed whether there was any worsening. Then, as Tim reported some breathing problems, I also performed an examination of the respiratory system. There was some sort of wheezing, but that, according to his records, could be traced to his COPD, a chronic condition mostly attributable to smoking (depends on demographic). His breathing was also restricted by the pain in his ribs. However, it was then I saw - a mole next to the left nipple. Medical professionals have seen everything - blood, mucus, snot, tears and all. Moles are quite common in the general population. They are black 'spots' dotted around the skin. Some might find them unattractive, while I find them intrinsically human. Even when they go wrong. That mole struck me as weird since it did stand out in terms of size and contour - it was comparable to the size of a 50p coin, irregular in edge and heterogenous in colouration. It was also slightly elevated. I grabbed my torch and shone on it to get a clearer view - it got two friends lying by its side, both of which were smaller than half the size of a 1p coin, barely detectable by my naked eye. I got a pair of gloves from the counter and started examining it. It was not tender and was fixed to the underlying tissue. It was hard in consistency. Alarmed, I started doing a complete lymph node examination, paying particular attention to the armpits (axillae) and neck (cervical lymphatics). I felt a lump over the axilla, but it may well be a sign of prostate cancer metastasis. Or not. Maybe this lump, alongside the moles, were the ones held responsible. Maybe the prostate was fine to begin with.
Picture of Melanoma (superficial spreading type);
(This picture is extracted from Wikipedia- not the real patient)
What do I mean by fine, you might ask? It's a cancer after all. Prostate cancer is usually an 'incidentaloma' on a scan, meaning that it's not actually important enough to warrant consideration. Contrary to popular belief, in medicine, we only fix things if they are sufficiently serious to cause worry (for those who question the utility of cosmetic surgery, we need to recognise patients' emotional suffering stemming from their appearance). A cancerous lesion in the prostate may sound alarming to a lay person, to medics, unless it causes overt symptoms and signs, it's usually dismissed as a very slow-growing lesion that doesn't get too much worse over time. The patient is likely to die from other causes. [4] Recently, there had been a rise in interest in early diagnosis - where the legendary PSA (prostate specific antigen - a biomarker for prostate cancer) test is advocated. This is why I said, in my previous blog post 'Cracked: Why James Davies is doing more harm than good', that blood tests and biomarkers might not represent the actual suffering of the patient. PSA is not as reliable as one might think. It isn't comparable to an OGTT (oral glucose tolerance test) where we can safely say that a patient has a high chance of suffering from diabetes mellitus. [5] One of the major caveats is that a low PSA does 'not' mean one does not have prostate cancer. The same applies for those with a high PSA. That's why doctors usually do a PSA test only when the patient experiences symptoms, such as haematuria (blood in urine) and suprapubic pain (usually due to a growing mass pressing against the nerves of the region). Moreover, acting on the basis of a high PSA only may entail more damage than the cancer itself. The patient is inadvertently subjected to more testing and all these tests have their risks. To diagnose prostate cancer, apart from serial PSA tests (yes, not just one, because we want to deduce the trend and see if there are any dramatic increases along the horizontal line of temporality), we need imaging. We need a technique called trans-rectal ultrasound to see about the prostate and any abnormalities therein. Sometimes, an MRI is required. [6] Such imaging might be safer than CT or X-Ray since they do not require any radiation. However, MRI studies may require the infusion of contrasts, which can lead to side effects. Moreover, such imaging is done to supplement biopsies. In prostate cancer, a needle biopsy is performed. It means that a section of the tissue is extracted and examined under a microscope. The aggressiveness of the cancer is then assessed according to the Gleason Score, which adequately predicts survival rates. [7] During the biopsy process, many things can happen. This includes injury to other organs and infection.
All in all, acting on a high PSA does not only augment the patient's worry. It also causes horrible consequences and unnecessary risks. Moreover, prostate cancer, even if diagnosed, usually follows an insidious course that it is more likely for the patient to die of other causes.
[8] Prostate Cancer Diagram.
I asked the consultant-in-charge about Tim's condition. He said that Tim was admitted a few months ago, presenting with severe haematemesis (vomiting with blood) and epigastric pain. He was suspected of having a stomach ulcer. Therefore, a digital rectal examination was performed (basically the only physical exam people laugh at) to examine if he also had melaena - black (or tarry), sticky stool. It was then discovered that his prostate was rather hard and large. Therefore, tests were ordered. Tim had no other symptoms, including those of the urinary tract. Gleason Score for the lesion was high. He was later given drugs for his ulcer. He also underwent a biopsy and was diagnosed prostate cancer. Due to that he complained of back pain and breathing problems, X-Rays were done. The Chest X-Ray looked normal and the Spinal X-Ray showed lytic changes over the vertebrae. However, those findings were dismissed as mere 'atypical' changes. Tim's condition was called 'atypical' because it did not conform to the natural behaviour of the cancer. He was subsequently put on systemic (whole body) chemotherapy, since medics were convinced that the cancer already spread to the bones. At no point did anyone check other parts of his body. Everyone naturally assumed that the prostate was the source of the cancer.
I raised my suspicions and the consultant immediately checked the lesion. At the meantime, further questions were put forward to Tim. He said that the mole had been there for years. It changed colour and grew in size about a year ago but he thought it must be got to do with the weather, so refused to consult his GP about it. He also enjoyed sunbathing and did so, prior to hospitalisation, two times a day. He also spent over four months in Spain every year, soaking in the glory of the sun. We took some of the tissue of the mole (biopsy) and assessed it under the microscope. The results came back and confirmed it was a melanoma. Judging by the timeline and the fact that UV exposure is a major risk factor [9], it was very likely that he got the melanoma first. The prostate cancer was a red herring. It was also likely that the lytic bone metastases originated from the melanoma instead of the prostate cancer. [10]
X-Ray showing metastases to the pelvis (Osteolytic, as evidenced by diffuse, patchy regions of radiolucency); extracted from: https://classconnection.s3.amazonaws.com/151/flashcards/2071151/png/osteolytic_bone_metastases1352150503811.png
The treatment regimens for melanoma and prostate cancer are very different, since they have different pathophysiological origins and mechanisms. I'm not going to bore you with the details but generally speaking, in metastatic prostate cancer, we aim to reduce the activity of testosterone and take care of the metastases through radiotherapy (bone). Debulking might be necessary - this means that if a lesion is getting too big, to the extent that other organs dysfunction due to mass effect, surgery can be adopted to remove it or make it smaller. For metastatic melanoma, we focus on giving systemic chemotherapy (different to those used in metastatic prostate cancer) or immunotherapy, since the natural course of melanoma is influenced heavily by the immune state of a patient (that's why there are instances called 'spontaneous regression', where the patient suddenly reports cancer-free due to the enhancement of one's immune system through non-medical means). Target therapy may also be beneficial. [11, 12]
This also brings out an important point. As medics, we don't always have enough time to deal with a patient. There are loads of stuff to do and the running up-and-down is real. I cannot imagine how tough it is to take care of so many affairs when the clock is constantly ticking. However, referring to Tim's case, one mistake led to a wrong diagnosis. A wrong diagnosis led to a wrong treatment plan. He experienced additional suffering because of wrong clinical decision-making. We're better than this. We should be more vigilant and more open to possibilities.
*Fake name- as mentioned above, all true particulars are replaced to protect patient anonymity.
[1] Chen H, Ma X, & Bai Y. (2012). Radiographic characteristics of bone metastases from hepatocellular carcinoma. Współczesna Onkologia, 5, 424-431. https://doi.org/10.5114/wo.2012.31773.
[2] Wu X, Li F, Dang L, Liang C, Lu A, & Zhang G. (2020). RANKL/RANK System-Based Mechanism for Breast Cancer Bone Metastasis and Related Therapeutic Strategies. Frontiers In Cell And Developmental Biology, 8. https://doi.org/10.3389/fcell.2020.00076.
[3] Zajączkowska R, Kocot-Kępska M, Leppert W, Wrzosek A, Mika J, & Wordliczek J. (2019). Mechanisms of Chemotherapy-Induced Peripheral Neuropathy. International Journal Of Molecular Sciences, 20(6), 1451. https://doi.org/10.3390/ijms20061451.
[4] Pendick D. (2020). Prostate cancer lives as it is born: slow-growing and benign or fast-growing and dangerous - Harvard Health Blog. Harvard Health Blog. Retrieved 13 November 2020, from https://www.health.harvard.edu/blog/prostate-cancer-lives-as-it-is-born-slow-growing-and-benign-or-fast-growing-and-dangerous-201308146604.
[5] Edmunds K. (2020). Why a one-off PSA test for prostate cancer is doing men more harm than good - Cancer Research UK - Science blog. Cancer Research UK - Science blog. Retrieved 13 November 2020, from https://scienceblog.cancerresearchuk.org/2018/03/06/why-a-one-off-psa-test-for-prostate-cancer-is-doing-men-more-harm-than-good/.
[6] Tests to Diagnose and Stage Prostate Cancer. American Cancer Society. (2020). Retrieved 13 November 2020, from https://www.cancer.org/cancer/prostate-cancer/detection-diagnosis-staging/how-diagnosed.html.
[7] Egevad L, Granfors T, Karlberg L, Bergh A, & Stattin P. (2002). Prognostic value of the Gleason score in prostate cancer. BJU International, 89(6), 538-542. https://doi.org/10.1046/j.1464-410x.2002.02669.x
[8] Localised prostate cancer. Cancer Research UK. (2020). Retrieved 13 November 2020, from https://www.cancerresearchuk.org/about-cancer/prostate-cancer/stages/localised-prostate-cancer.
[9] Watson M, Holman D, & Maguire-Eisen M. (2016). Ultraviolet Radiation Exposure and Its Impact on Skin Cancer Risk. Seminars In Oncology Nursing, 32(3), 241-254. https://doi.org/10.1016/j.soncn.2016.05.005.
[10] GT Fon, WS Wong, RH Gold and LR Kaiser. Skeletal metastases of melanoma: radiographic, scintigraphic, and clinical reviewAmerican Journal of Roentgenology. 1981;137: 103-108. 10.2214/ajr.137.1.103.
[11] Bhatia S, Tykodi SS, & Thompson JA. (2009). Treatment of metastatic melanoma: an overview. Oncology (Williston Park, N.Y.), 23(6), 488–496.
[12] Chopra N, Nathan PD. (2015). Trametinib in metastatic melanoma. Expert Rev Anticancer Ther. 15(7):749-60. doi: 10.1586/14737140.2015.1060127. PMID: 26107021.