Prostate cancer is the most common malignant condition and a very serious concern in older men throughout Europe, both in our region and more developed countries with a high percentage of senior population. Over 95% of all malignant prostate tumors are located in the gland tissue, also known as the adenocarcinoma, so prostate cancer is also often called prostate carcinoma.
Prostate cancer is the second most common form of carcinoma and the fifth most common cause of death in men worldwide. Furthermore, it has been the chief cause of death in Europe for several years now. It occurs in three quarters of the patients between the age of 50 and 75, although recently it has been affecting younger men as well, presenting an additional challenge to global medicine. According to research conducted in the USA, more than 10% of newly discovered prostate cancer occurred in men below the age of 55.
As opposed to other forms of cancer, we still don’t know enough about this particular sort, despite numerous studies. The leading risk factors for prostate cancer are age, ethnicity, genetics, as well as family history. Other risk factors that may be connected include nutrition, obesity, insufficient physical activity, inflammations, infections, hyperglycemia, exposure to various chemicals and ionizing radiation, as well as frequency of ejaculation.
Many studies agree that in order to effectively prevent prostate cancer, men should take care to live as healthily as possible: do regular physical activity in a healthy environment, have a varied nutrition that avoids saturated fats and red meat but includes a lot of fruits and vegetables, anti-oxidizing micronutrients, etc. Vitamins E, D, and selenium are the most commonly added nutritional supplements whose effects can decrease risk. In addition to following general rules of healthy living, the future of effective prevention of prostate cancer most likely lies in individual assessments based on additional molecular analyses of certain biomarkers.
Modern-day diagnosis of prostate cancer relies on detecting increased levels of PSA in the
serum. The amount of patients who visit an urologist due to noticing the showing symptoms
related to prostate cancer is rather small. In accordance with the EAU recommendations,
diagnosing prostate cancer follows these four steps:
– confirm the primary clinical diagnosis,
– define the stage of the condition,
– assess the overall patient health and estimate an approximate life expectancy,
– perform screening and early detection programs.
Much like other forms of cancer, the histopathological tissue analysis is the key to diagnosing prostate carcinoma. The cancer is most often found in the tissue taken via the
needle biopsy of the prostate; it can also be found, albeit more rarely, after a surgery to treat prostate gland enlargement (prostatic hyperplasia). Prostate carcinoma is categorized as one of the rare forms of carcinoma whose aggression varies from pretty harmless (such as the indolent prostate cancer) to most aggressive. As such, in order to treat these varied forms, we have to apply an equally varied range of methods and treatments. In follow up on the patient regardless of the treatment method chosen, it’s important to regularly check up on the PSA levels, which are currently the only reliable indicator of the cancer progression or the biochemical recurrence.
The discovery of prostate-specific antigen (PSA) at the end of the ‘80s has led to a large number of clinical trials focusing on early cancer detection, as well as screening programs, which means diagnostic treatments of men without any symptoms. Up to 50% newly discovered prostate carcinoma in asymptomatic men shows histopathological signs of the so-called incidental carcinoma, the same one found in autopsies on patients who had never been treated for prostate cancer. As such, it is safe to assume that the majority of such men will not develop any sort of serious disease during their lifetime, and won’t need active treatments.
Prostate cancer, which probably will not become symptomatic until the end of the patient life and pathohistologically mimics incidental prostate cancer in the autopsy results of men who did not die of prostate cancer, is called indolent prostate cancer. This term is used only for newly-discovered carcinoma that simultaneously fulfills clinical and pathological criteria.
Clinical cancer diagnosis is based on clinical examination, determining the levels of PSA in the serum, as well as a histopathological confirmation acquired via needle biopsy of the prostate. Symptoms that may be connected to prostate cancer are usually urinary incontinence, lower urinary tract symptoms (LUTS), presence of blood in the urine
(hematuria) or the sperm (hematospermia), erectile dysfunction, pain in the pelvic or lumbar area, or inexplicable weight loss. Three quarters of prostate cancer patients are
estimated to not have had any symptoms – or very mild, urinary ones that they did not even take as symptoms – at the moment of confirming the diagnosis.
One of the most basic parts of the physical exam is a DRE – a digital rectal exam. It is also normally done for patients with symptoms of LUTS. The main goal of this examination is to estimate the size and consistency of the prostate, feeling for irregularities such as hard spots or lumps on the surface of the prostate gland. If any are found, chances of prostate cancer are quite high. Even if the DRE is negative, we cannot exclude a possibility of malignant changes.
PSA is a protein produced by not only prostate cells (regular and those which have undergone benign changes), but also cancer cells. The highest concentration is in the sperm.
A portion of the secreted PSA can also be present in the blood, usually tied to certain proteins. This portion is measured by the serum test, which gives us the total PSA levels in the serum. In addition to the total PSA, we can also measure free PSA, created by proteolysis. Despite the fact that PSA is practically only used to diagnose prostate cancer, it’s not regarded as a tumor marker as such. Namely, its value depends on certain non-malignant processes that take place in the prostate, such as benign prostatic hyperplasia (BPH) or prostate inflammation (prostatitis). In many countries, a normal total serum PSA level is ≤4 ng/mL, which is still considered an average result in the global male population.
However, recent studies on younger men have shown that these levels are, on average, significantly lower.
In order to officially confirm and diagnose prostate cancer, we need a positive histopathological analysis via needle biopsy of the prostate. The indications for doing the
biopsy are based on PSA serum levels and/or a positive (pathological) DRE of the prostate, rarely ever just based on suspicious results of certain screenings. The needle biopsy of the prostate is a relatively unpleasant and uncomfortable examination for the patient, and it can lead to serious complications, so experts take ample care to avoid unnecessary biopsies.
The procedure can be done perineally, but it is more commonly done transrectally, using a transrectal ultrasound (TRUS). The sample number in the basic prostate biopsy depends on the size of the organ.
It is recommended to take at least eight samples if the prostate is approximately 30 mL, ten or twelve samples if prostate is larger, and some additional samples of ultrasound suspicious areas in the prostate. In case the histopathology results are positive, we have not only a confirmation of the type of tumor, its aggression and
spread, but also a quality report that contributes to finding the best possible treatment option for every patient individually. The histopathological diagnosis of prostate cancer is one of the most demanding and complex tissue analyses, to the point where most developed countries rely on the expertise of uropathologists instead of general pathologists.
Following a good clinical practice, it’s becoming increasingly common to include at least two pathologists in diagnosing prostate cancer, and do a double analysis of the needle biopsy results.
Magnet resonance imaging (MRI) is the most efficient imaging method in prostate cancer diagnosing to determine the stage of prostate carcinoma. Today, a multi-parametric magnet resonance (mpMRI) is used to determine the local stage of the disease, whereas a general MR is useful to additionally estimate regional and other lymph nodes and organs. All of these procedures are guided by the standardized prostate imaging reporting and data system (PI-RADS). The discovered changes are categorized based on a 5-point scale. PI-RADS ≥3 are of particular importance because it determines a high probability of clinically significant, aggressive forms of prostate cancer.
In recent years, combining the mpMRI with TRUS has enabled further development of the so-called fusion guided prostate biopsy – an
improvement on the ordinary needle prostate biopsy – which can be done via cognitive method or computer fusion of mpMRI and TRUS picture. During the cognitive method, the researcher attempts to mentally project each individual image received from the mpMRI onto the live TRUS image, and as such find the most suitable location for the biopsy. “Real” fusion, on the other hand, we rely on the computer to combine the aforementioned imaging.
Due to the heterogenic nature of the prostate cancer and massive differences in aggression and consequent progression of the disease, the estimates of the patient’s life expectancy and general health are incredibly important when planning screening, diagnosis, and treatment. Nowadays, we don’t have a unique, uniform age limit for various active treatments of prostate cancer, but it is generally recommended to consider the estimated patient’s life expectancy of more than ten years. Of course, it is often not possible to strictly adhere to such criteria in practice, since it’s necessary to take into account the patient wishes and their various psychological, cultural, and social environments when deciding whether or not to actively treat the disease and how.
There are various stages of aggression when talking about prostate carcinoma: from the indolent sort that only requires active surveillance i.e. delayed/inactive treatment, to highly aggressive sorts that usually require a multidisciplinary approach. This has led to the development of a broad range of possible treatments as a result.
In cases of patients older than 65 and suffering from an indolent or low-risk prostate carcinoma, the most common treatment is a delayed one. The fact is, overdoing treatment of this sort of cancer often leads to unnecessary complications and a significant decrease in the patient’s quality of life. The key factor in active surveillance is to delay more aggressive active treatment for as long as possible, and retain quality of life. These patients are monitored and undergo regular examinations (PSA, rectal exam, prostate biopsy), and in some cases determining biomarkers and/or doing an mpMRI. Any exceptions during active surveillance, is an indication we should move onto one of the forms of active treatment.
Strictly adhering to the protocol of active surveillance allows patients to avoid various dangers. However, it is important to raise awareness in younger men that there haven’t
been enough long-term studies done to clearly confirm the efficiency and safety of active surveillance for the population of young men. Watchful waiting is a palliative form of care reserved for older men who, due to preexisting conditions, are advised against active treatment until the cancer progresses, while for some of them, a hormone blockade would suffice.
When it comes to active treatments of localized and locally advanced prostate cancer, we can often turn to surgical treatments, radiation, and any other new method – alone or in conjunction. Treating via medication is reserved for late stages of prostate cancer first and foremost, as well as a part of so-called multimodal treatment.
Surgical treatment entails performing radical procedures such as radical prostatectomy – which has been the main method of treating prostate cancer for over a century, ever since its first mention in 1905. The procedure includes the surgical removal of the entire prostate with an intact capsule and seminal vesicles, and performing a urethrovesical anastomosis – creating a watertight connection between the urinary bladder and urethra. The main goal of this surgery, no matter the approach, is to remove the prostate tumor while retaining as much urinary continence and erectile function as possible.
The recent development of minimally invasive surgical techniques has enabled the radical prostatectomy to be performed laparoscopically or robot-assisted.
Both methods have been highly beneficial for patients, and as such, there is little difference between them. Oncological and functional results of radical prostatectomy (no matter the surgical technique used) are statistically comparable – in this regard, these two methods are neither better nor worse than each other.
Regional pelvic lymphadenectomy (pelvic lymph node dissection) has no statistical proof of higher survival rate or oncological outcome of the surgical treatment, but it does
give important information about the cancer progression, so it’s generally recommended in patients with more aggressive forms of cancer. In order to estimate whether or not the regional lymph nodes need to be removed on a case-by-case basis, we have a variety of nomograms that aid us in predicting the probability of positive lymph nodes. Erectile dysfunction is a fairly frequent post-operative side effect, and in some patients significantly decreases the quality of life after radical prostatectomy.
Attempting to preserve the nerves, meaning the neurovascular bundles and parasympathic pelvic plexus, can significantly decrease these side-effects and have a positive, albeit indirect effect on urinary continence after radical prostate surgeries, as well. There are several key factors that contribute to a successful surgery: the appropriate surgical technique in combination with extensive experience of the surgical team, especially in regards to the precise preparation of certain layers of pelvic floor tissue and the careful forming of the urethrovesical anastomosis while preserving the integrity of the bladder neck.
Radical prostatectomy is the most frequent method of locally treating prostate cancer, with
very good oncological results. 20-40% of patients who have undergone this surgery have
been confirmed to experience increased PSA in the serum, known as the biochemical
recurrence or relapse of the disease.
Total PSA is the most important factor in discovering a biochemical recurrence of prostate cancer, because it after a radical prostatectomy becomes a true tumor marker. In 2016, both the American Urological Association and the European Association of Urology unanimously accepted a PSA value of ≥0.2 ng/mL as a threshold value which means a biochemical recurrence after radical surgery and prostate cancer relapse, and this is still accepted to this day. Despite the fact that most recurrences occur within three years after the radical prostatectomy, it is necessary to regularly monitor the patients for at least another ten years. It is also important to correctly interpret the biochemical aspects of cancer progression, meaning that every PSA increase above 0.2 ng/mL isn’t necessarily indicative of a clinical progression to metastasis. The limit of ≥0.2 ng/mL is used as an indicator of further necessary treatment that is even more efficient if introduced early.
Modern imaging methods, especially a PSMA PET-CT, today are able to be used in case of very low PSA levels and accurate determine local progression or metastasis localization, which significantly contributes to selecting the appropriate additional course of treatment.
Cause of death in prostate cancer patients is metastatic tumor which can’t be cured, and so different treatments can really only slow it down. Introducing hormone therapy can prolong the patient’s life by several years, and additional, second-generation hormonal therapy or/and chemotherapy by a few months more. In essence, medicine begins its fight against mortality statistics caused by prostate carcinoma before the metastasis is even confirmed, imminently after local treatment.
Based on various diagnostic results before and after local treatment – so-called risk factors – we can estimate the probability of progression towards metastatic cancer, and apply a timely course of treatment to slow it down or even prevent it. Monitoring risk factors in prostate cancer patients who had undergone radical prostatectomy is important not only for evaluating surgical success, future forecasts, and treatments, but also for a timely start of further treatment.