Diagnosis: “clinically insignificant cancer”. Man has to live with him

Three specialists join forces not only to care for health, but also to educate patients with prostate cancer. In an interview with Medonet, the doctors created a short compendium of current knowledge about this disease. The most common malignant neoplasm and its treatment are discussed by urologist Dr. Tomasz Konecki, oncologist-radiotherapist Dr. Łukasz Kuncman and clinical oncologist Dr. Maja Lisik-Habib. Experts also explain when there is “clinically insignificant cancer” and what it means.

1. The statistics of the National Institute of Oncology show that in 2019, 17 patients developed prostate cancer. men, which is over 20 percent. the total number of cancers detected in men
2. One of the most important stimuli for the development of prostate cancer is testosterone
3. In the case of this tumor, diagnostics is extremely important
4. More current information can be found on the Onet homepage.

To those who have heard about the prostate, but do not know it, we can say that …

Dr Maja Lisik-Habib: … the prostate is a gland, also called the prostate gland, or the prostate, and part of the male reproductive system. Her role is, inter alia, secretion of a whitish liquid carrying the sperm. It is located in the smaller pelvis below the bladder and in front of the rectum. Since the urethra runs through it, the first symptom of an enlarged prostate is often problems with urinating due to mechanical pressure on the urethra. Prostate hypertrophy does not mean prostate cancer.

But prostate cancer?

It is the most common malignant neoplasm in men. It was ahead of lung cancer statistics. The risk increases with age, more than half of the patients are at least 70 years old. This cancer rarely occurs before the age of 50, although world statistics and experience show that more and more prostate cancer attacks younger men, aged 40-50.

Dr. Tomasz Konecki: I was browsing the last available report of the National Institute of Oncology for 2019, which gives the number 17. patients per year. Probably in 2022, taking into account the increasing incidence, we will see even more cases.

Dr. Łukasz Kuncman: Older societies have a higher incidence of the disease, as can be seen in the statistics. In the Polish population, this cancer accounts for over 20%. the total number of cancers in men, while the mortality rate is 10%. overall cancer mortality in men.

What are the causes of the disease?

Dr Lisik-Habib: Prostate cancer is the result of several factors: genetic (family), environmental, age, and sex hormones. Undoubtedly, testosterone is a fuel for cancer cells and one of the most important stimuli for the development of this cancer. In addition to the most important factors, i.e. age and the effect of testosterone, one of the reasons for the development of prostate cancer are mutations in the DNA repair genes (BRCA1 and BRCA2), as in breast cancer. Also environmental factors, such as diet, play a role. It is believed that obesity and a high-fat diet associated with the occurrence of other malignancies and cardiovascular diseases may also contribute to the development of prostate cancer.

But for this tumor, the diagnosis works.

Hence, two things contribute to high detection and increased morbidity: an aging population and the massive performance of PSA tests. Therefore, in developed countries such as the USA, New Zealand or Australia, and in Western Europe, the detection rate is definitely at the highest level. In addition, a large proportion of neoplasms in elderly patients are clinically insignificant neoplasms.

What does this term mean?

Dr. Konecki: The term “clinically insignificant cancer” originated in the USA and means a disease that during the foreseeable life (given by fate, biology or God) of the patient’s life will not cause him any harm. One that he might not treat because he wouldn’t die because of her. He will die with her. Undermining the sense of screening has translated into the view in our community that prostate cancer is harmless. Hence the criticism of screening tests, because then why do they? However, let’s not forget that 30% of prostate cancer dies. sick, therefore in Poland, where 17 thousand are ill every year. people, over 5 thousand die annually. Such mortality should not be underestimated. The disease often progresses very slowly but can be fatal. Today, the key question is: what to do after the diagnosis of prostate cancer, so that the therapy is as little invasive as possible for the patient and that the patient does not die from it.

However, PSA tests were not abandoned.

Two decades after the introduction of PSA in the United States, between the 80s and 90s, prostate cancer mortality fell by 30%. It is worth mentioning because at that time patients were treated by surgery or radiotherapy. Today we have a lot of modern drugs that extend life more effectively. Please note that nearly a third fewer patients died of prostate cancer. Such a decrease was not observed even after the introduction of mammography tests for breast cancer in women. In the case of mammography, no one protests that many lesions are detected, which turn out to be benign … If we diagnose prostate cancer early, the part will always be irrelevant.

Dr. Kuncman: High detectability can be beneficial. I think that every oncologist, radiotherapist-oncologist, and urologist will agree that whether a tumor is clinically significant or not can only be determined after a series of tests. The second aspect is appropriate therapy. A specialist dealing with local or systemic treatment, after determining the risk factors, knows what the best possible treatment to propose.

Dr. Konecki: Exactly, the maturity of the system and the intelligence of doctors contribute to the follow-up, but screening should not be forgotten.

Let’s introduce readers to this research.

PSA is the main marker used in screening, the equivalent of mammography in women. It is a protein specific for the prostate gland, a fairly sensitive marker that allows the detection of sick people, but it is increased not only due to prostate cancer. We are waiting for more effective markers that would be equally sensitive and at the same time more specific. We would like to have a marker of clinically relevant disease.

Are treatments for clinically significant and insignificant prostate tumors very different?

Since the definition says that a disease that is clinically insignificant in the course of a patient’s life will not harm him, the question arises how to include it in a specific recommendation. Remember that medicine is based on statistics, while the treatment of patients is individual. We sit face to face with a specific patient and we must establish recommendations. The prognosis of whether a given neoplastic disease is clinically significant or not is related to the answer to the question of how long a patient’s life is ahead of him. The answer is basically impossible, although we have a scientific definition based on certain criteria. Only after a biopsy, we can assume whether the disease will be clinically insignificant, i.e. that it should not threaten the patient within 15-20 years. We observe such people. However, it is not known what to do with a young (e.g. 50-year-old) man who is about 40 years old. The issue is complex, the definition works, there are criteria, but it is not easy to reassure a particular patient about the irrelevance of his oncological disease.

The 2022 National Health Test of Poles XNUMX shows that men do not like to be tested for prostate cancer. How to encourage them to do so?

Dr Lisik-Habib: It should be emphasized that in recent years considerable progress has been made in the treatment of neoplastic diseases. We are able to cure more and more of them at an early stage, and we are able to extend the life of people suffering from advanced forms of cancer. The statement that cancer is not a sentence is true. The family – wives, partners, mothers and daughters – plays a significant role in the admission of men to screening tests. So we urge women to pay attention to their men’s health.

And once prostate cancer has been diagnosed, what are the treatment options?

Dr. Kuncman: We use local treatment mainly when the disease is advanced locally or within the pelvic lymph nodes. We treat with radical radiotherapy (often combined with hormone therapy) and radical prostatectomy.

Probably the urologist will add something from himself?

Dr. Konecki: I liken treating prostate cancer to preventing a volcanic eruption. The urologist would like to extinguish the volcano before it erupts. By an outbreak, I mean the appearance of metastases. I want to extinguish the volcano, that is, destroy the growth in the prostate by removing the gland (radical prostatectomy) or by subjecting the patient to radiation therapy. This is the case when we detect cancer quite early. There is no adipose tissue around the prostate gland, so it is difficult to take all disease covered with healthy tissue as there is no tissue margin. Nearby is the urinary sphincter, the rectum on the back surface of the gland, and the potency nerves on the sides. The nerves are surrounded by adipose tissue, so here we can move away from the prostate, but at the cost of worsening potency. The development of surgical techniques has led to the use of minimally invasive methods – laparoscopy and robotic methods, including the Da Vinci robot. Thanks to this, we can remove the prostate gland along with the disease, while maintaining urine and sexual function. The most desirable for surgical therapy are patients with a clinically significant disease (which may harm them in the future) but limited to an organ.

So surgery has made an amazing leap forward?

From the 80s, open prostatectomies were performed. The organ was removed from a vertical (vertical to the patient standing) skin incision; from the navel to the pubic symphysis 15 – 17 cm long. In the second half of the 90s, the laparoscopic techniques used in Poland for over 20 years were developed. They involve the insertion of tools through small cuts in the abdomen, often referred to as a keyhole. Additionally, the surgeon has an optical system with a camera. The tools are in his hand, and he observes the operating field magnified on the screen. Laparoscopic techniques shortened hospitalization. After an open prostatectomy, the patient stayed in the hospital for a week, and after laparoscopy, he returns home after two days. Robotic techniques that replace classic laparoscopy minimize, inter alia, sphincter injuries. At the moment, up to 85 percent in the US. the operation of the prostate gland uses a Da Vinci robot. This gives greater accuracy, which translates into better urinary incontinence. However, the robot is not autonomous, it does not operate by itself, everything is decided by the surgeon at the console. If the operation is performed by an experienced surgeon, urinary continence recurs in up to 95%. patients.

What if the disease goes beyond the organ?

Surgical action is also possible, but the risk of positive surgical margins, ie tumor cells are present in the incision line. For the patient, this means that the disease has potentially not been completely removed and will require complementary radiotherapy or so-called rescue radiotherapy, so one treatment will become two. The situation is similar in the case of patients with lymph node metastases. If the removed lymph nodes along with the prostate gland reveal the presence of cancerous cells in the histopathological examination, this will be the reason for the decision to use radiotherapy.

Let’s move on to discussing radiation therapy.

Dr. Kuncman: In many places in Poland, there are multidisciplinary teams which, based on the stage of the cancer, how many comorbidities the patient has and their preferences, are able to choose the appropriate treatment method. According to studies, radiation therapy is comparable to prostatectomy, while some patients benefit more from radiation therapy and some from radical prostatectomy. The decision is made individually for each patient on the basis of clinical factors and after discussing the complication profile of each method with him.

What are these complications?

In the case of radiotherapy, in a few to a maximum of a dozen or so percent. patients may develop pollakiuria, lower urinary tract infections, and diarrhea. Meanwhile, after radical prostatectomy, problems with urinary incontinence and potency occur more often than after radiotherapy.

Radiation therapy has also developed a lot recently.

We have two main methods of treatment – irradiation from external fields (teleradiotherapy) and treatment with brachytherapy consisting in inserting applicators into the prostate gland. Irradiation from external fields is a less invasive method in which we use extremely precise linear accelerators. We use dynamic techniques, we visualize the movement of the prostate, we see exactly where it is located and we are able to very precisely irradiate it. In less advanced tumors, stereotaxic radiotherapy is also used, including radiotherapy with a robotic system.

The terms radical prostatectomy or salvage radiotherapy can scare many.

Dr. Konecki: The above terms in Polish have a slightly unfortunate overtone. Radical prostatectomy means complete, in the sense of removing the entire disease, and not dangerous or ruthless treatment. Salvage radiotherapy is associated with the last resort, and yet it is a therapy that is supposed to cure the patient.

Dr. Kuncman: The word “radical” emphasizes the aspect of either removing all disease or being irradiated so as to destroy the tumor. In contrast, salvage radiotherapy is aimed at very early detection of possible recurrence after prostatectomy, in order to heal the patient locally. Therefore, it is not so much saving against something as it allows limiting the possibility of metastasis formation. Early salvage radiotherapy, rather than adjuvant after prostatectomy, is the preferred form of treatment at the moment. I would like to emphasize that radiotherapy now is completely different from the one used many years ago. It is a very precise form of treatment where a high dose of radiation is administered, while protecting tissues and organs in the immediate vicinity.

Will a patient diagnosed with metastatic prostate cancer not be written off as well?

Dr Maja Lisik-Habib: Treatment of cancer located outside the prostate gland, i.e. in stage IV, is a task for a clinical oncologist who uses the so-called systemic treatment. It is about hormone therapy, chemotherapy, molecularly targeted therapy and immunotherapy. In the case of prostate cancer, the basic method of systemic treatment is hormone therapy, which aims to lower the testosterone concentration to the so-called castration values, i.e. very low. They can also be obtained through the so-called surgical castration – removal of the testicles, although most patients choose hormonal treatment. It consists of giving hormone injections every month, every three months or once every six months. Unfortunately, after a few years, this therapy causes the development of castration resistance, i.e. the tumor’s insensitivity to basic hormone therapy.

I understand that oncologists deal with this phenomenon?

In this case, oncological treatment can take two forms. First of all – chemotherapy, administered in the form of intravenous drips once every 3 weeks. Patients are usually treated on an outpatient basis, i.e. they receive a drip and go home. Second – we can use the so-called modern hormone therapy in the form of second-generation hormonal drugs, which lead to a stronger blockade of the production of male sex hormones. Every patient with prostate cancer requires consultation with a clinical oncologist when he develops castration resistance. Another group of patients who should visit a clinical oncologist are those diagnosed with stage IV disease. In this case, we can add chemotherapy to the hormone therapy often used by urologists.

And molecularly targeted treatment?

A novelty is the possibility of using PARP inhibitors, i.e. drugs targeting a specific diagnosed genetic disorder. Unfortunately, this therapy is not reimbursed by the National Health Fund. Drugs that directly affect bone metabolism and delay the occurrence of adverse bone events play an important role in the treatment of diseases with bone metastases.