Prostate cancer. Diagnosis and treatment. New perspectives.
Prostate cancer is now a major public health problem. It is the second most frequently diagnosed cancer in man today, being the 4th cause of cancer death in man in the western countries. We know that in the US alone, for example, 28,900 men died from prostate cancer in 2003. In 2005, 230110 men with prostate cancer were diagnosed in the same country, a number that would rise to 38,000 in 2025. The risk of a Western man to be diagnosed a lifetime prostate cancer is 16.6%. In Europe, 247 men die each day from this disease.
Studies show that the incidence of prostate cancer has been increasing in recent decades. The causes are unclear, and although the more aggressive strategies for early diagnosis may partly justify this increase, other causes associated with diet, lifestyle, or the environment can not be ruled out.
The incidence of prostate cancer increases with age, meaning it is not a disease of the young man. However, it has been observed the appearance of this neoplasia in ages more and more precocious. Most guidelines still recommend annual screening at age 50 or at age 45 for high-risk groups such as blacks or those with first-degree relatives with a history of prostate cancer. However, the number of cases under 50 is increasing, so many urologists advise regular consultation from the age of 40.
We are still unaware of the causes of this type of cancer. Our knowledge is incomplete regarding risk factors. In addition to age and family history, other factors seem to be important. In fact, the risk of developing prostate cancer appears to vary from population to population, being much more frequent in Western countries such as the US, Canada, and Europe than, for example, in Asian countries. On the other hand, the risk is higher in blacks.
Diagnosis of prostate cancer
Generally prostate cancer develops without any symptoms only manifesting at a very advanced (disseminated) stage, already without possibility of cure. Contrary to what most people think, urinary symptoms rarely occur at an early stage. In fact, nowadays, 80% of cases are diagnosed by routine medical examinations performed on apparently healthy individuals without any complaints. Hence the importance of early diagnosis, a stage of localized disease to the prostate, still without symptoms, but curable.
Diagnosis is suggested by altering one of the following exams: rectal examination, PSA (prostate-specific antigen) blood test, and trans-rectal prostatic ultrasound. The rectal examination is a very simple and easy examination, which consists of digital prostatic palpation (with the finger), anal, which can provide important information about the volume, consistency and prostatic limits. Unfortunately some men still delay their trip to the urologist for fear of this examination. PSA is a substance produced by the normal prostate but whose blood values rise when there are prostate diseases, particularly in the case of prostate cancer. It is important to note that an increase in PSA does not necessarily mean the existence of prostate cancer, although it is necessary to exclude it.
The elevation of PSA occurs on average up to five years before the detection of any rectal anomaly. Special types of PSA, such as free PSA or complexed PSA, are now being used to increase specificity in the detection of prostate cancer, i.e., to decrease cases of false positives. Finally, transrectal prostatic ultrasound, although not recommended by all urologists, provides us with important information, such as the presence of suspected prostatic nodules, or the compromise of the gland’s limits. When any of these tests show suspicious changes, we should confirm the diagnosis of cancer by performing a prostate biopsy.
It is a technique that involves the collection of several fragments of the prostate, through the ultrasound and trans-rectal route, which are then sent for histological study in order to verify the existence or not of cancer. It is a simple examination, quite well tolerated by the patient and is done in the outpatient clinic without needing any hospitalization with only local anesthesia.
Treatment of prostate cancer
The treatment of prostate cancer depends essentially on two parameters: the patient’s age and the extent of the tumor. Older patients, with a life expectancy of less than 10 years, are usually treated only with hormone therapy, that is, with hormone suppression therapy since prostate cancer is hormone dependent depending on the stimulation by androgens such as testosterone . This hormonal suppression can be achieved with surgical castration (removal of the testicles) or chemically (with drugs that inhibit the production or performance of testosterone). It is a type of treatment that only acts temporarily (2 to 4 years), but which eventually allows patients of this age to die with their cancer and not their cancer.
When patients have a life expectancy of more than 10 years, younger, we must offer the patient a curative treatment, which is only possible if the disease is localized to the prostate. There are only three types of curative treatments for prostate cancer. What is considered most effective is radical prostatectomy, which involves the surgical removal of the prostate and seminal vesicles. It allows a 10-year survival of more than 90%, but with two important side effects: some degree of erectile dysfunction reaching 50-90% of patients and some urinary incontinence, usually transient, in the first few months, but which may be permanent between 3 to 10% of patients. As an alternative to surgery, some patients opt for external radiotherapy, a method with a lower commitment to sexual function and with no repercussions on urinary continence, but with lower healing rates than surgery and not without important and equally incapacitating side effects, such as rectitation , cystitis stems, or altered intestinal transit.
A third type of treatment has recently been introduced, prostatic brachytherapy, a form of interstitial radiotherapy, which consists of the introduction of radioactive seeds into the prostate under anesthesia. It is a method that has demonstrated cure rates that can be overcome with those of radical prostatectomy, in well-differentiated cancers, but with far fewer side effects, which is why it is increasingly preferred by patients. In the US, where it exists about 15 years ago, it is chosen by more than half of the patients.
Patients with metastatic disease (when cancer has spread to other areas of the body) are treated with hormone therapy. Hormone therapy, although not curative, can lead to long-term remission, allowing an excellent quality of life. However, over time, prostate cancer can progress despite hormonal therapy. It is not well known why this happens, but it progresses to a condition called hormone-resistant prostate cancer, in which about 70% of patients have metastatic bone. The skeleton is the main target of the metastasis of this type of cancer and when the disease reaches this stage there is no effective standard therapy and usually patients present severe and incapacitating complications such as intense bone pain, bone fractures or compression of neurological structures that are associated with a decrease in survival.
However, recent research in this area has made great strides, motivating renewed optimism. In recent years, some important new treatments have emerged, drawing new avenues in the treatment of these hormone-resistant and metastatic patients. In addition to the substantial improvement in pain therapy through the use of new analgesics, we have two new drugs with proven results. The first is zoledronic acid, of the class of bisphosphonates (a class of drugs that help rebuild and fortify the bone). This drug demonstrated a significant efficacy in the reduction of bone pain caused by metastases, as well as a decrease and delay in the appearance of bone complications of metastases such as fractures and the need for palliative radiotherapy. The introduction of zoledronic acid consisted of a new and effective treatment of bone metastasis complications of prostate cancer.
Studies are underway suggesting the possibility of using this drug at an earlier stage in order to prevent the appearance of bone metastases in patients at risk. The second drug recently introduced in the treatment of hormone-resistant patients is docetaxel, a type of chemotherapy that has been shown to increase the survival of these patients significantly, improving quality of life and providing new hope for hormone-resistant patients.
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One of the most fascinating areas in prostate cancer is chemoprevention, which consists of the regular administration of natural or synthetic chemicals, in order to prevent the onset and development of prostate cancer. Some natural products such as lycopene (abundant in tomatoes), phytosteroids (abundant in soy), selenium, or vitamins A and D, have shown promising results.
One of the most interesting studies in this area was the Prostate Cancer Prevention Trial, which demonstrated a 25% reduction in the risk of developing prostate cancer in men taking 5 mg finasteride daily, a drug that inhibits prostate-specific testosterone activity , already used for many years in benign prostatic hyperplasia. Another study, the REDUCE study, seeks to show similar results with another drug: dutasteride. The results are expected this year. This is undoubtedly an area of the future in oncology, which is only now taking its first steps.
In conclusion, although prostate cancer is very frequent, we now have many therapeutic alternatives, even in the more advanced stages of the disease, which allow the patient with prostate cancer to look forward to the future with hope.