Localized prostate cancer (prostate cancer): surgery

Active observation of patients with localized prostate cancer requires regular careful examination and determination of the level of PSA (for example, once for 3 months) without any treatment until symptoms of the disease or PSA value exceeds a certain level.

Conservative treatment of prostate cancer (prostate cancer) is generally adequate only for patients older than 70 years, with a limited (T1a) stage of the disease and an estimated life expectancy of less than 10 years. This form of the disease is often identified after TUR for prostate adenoma. In this case, prostate cancer will progress only in 10-25% of patients for 10 years, it rarely enough passes into a common form for 5 years. In patients with highly differentiated prostate cancer, the tumor usually grows and spreads slowly enough, for most older men there is no need for treatment under active surveillance.

Some retrospective studies with a follow-up period of 5-10 years call into question the need for radical treatment of patients with stage T1.

However, many arguments point to the use of expectant management in the early stage of prostate cancer. Aus et al. Found that of the group of patients with nonmetastatic prostate cancer who lived more than 10 years - 63% eventually died of the disease. There is no doubt. That patients with clinical stage of prostate cancer T2 who receive conservative treatment, have a high risk of developing metastases and death from this disease.

The data cited confirm the opinions of many specialists about the advisability of the tactics of active monitoring of patients in a group of patients with an expected life expectancy of less than 10 years. At present, there is no doubt about the provision that patients with clinical stage of prostate cancer T2. Which are observed or receive conservative treatment, have a high risk of developing metastases and death from this disease

Thus, the policy of active observation is contradictory, often doctors reject it.

At the moment, the most realistic alternative to the tactics of active surveillance in the localized forms of prostate cancer is radical prostatectomy and radiation therapy.

[1], [2], [3]

Radical prostatectomy

Radical prostatectomy (RPE) is the main method of treating patients with localized forms of prostate cancer. Indications for its implementation:

• localized forms of cancer (with T1-2);
• life expectancy over 10 years;
• absence of contraindications to anesthesia.

For the implementation of radical prostatectomy, two types of operative approaches are used: the back and the perineal. Both operational techniques are similar in terms of radicality, subsequent survival rate, the frequency of positive surgical margins. Some authors suggest a slightly higher incidence of the positive apical surgical margin with trail access as opposed to the more frequent anterior positive surgical margin with crotch access, but it is unclear what clinical significance this fact has.

Advantages and disadvantages of each of the described approaches have been discussed repeatedly. One of the main advantages of accessibility is the absence of contact with the abdominal cavity, which reduces the risk of postoperative intestinal obstruction, reduces postoperative pain and duration of hospitalization; the main disadvantages are the possibility of damage to the rectum, the difficulty of visualization of the neurovascular bundles, sometimes difficulties in the dissection of seminal vesicles. Advantages of retropubic access - the possibility of bilateral pelvic lymphadenectomy, as well as the preservation of all neurovascular bundles and potency. The main disadvantage is the need for an abdominal incision, which increases the length of hospitalization. The final choice is individual, it also depends on the preferences of the urologist (based on his experience).

One of the most common complications of radical prostatectomy, arising in 30-100% of cases is erectile dysfunction, which depends on the patient's age and operation technique (nerve-sparing or not). Another frequent complication is urinary incontinence, which occurs in 2-18% of patients after surgery (27.5% in mild form). Part of the problem of impotence and urinary incontinence is solved by some operational techniques: preservation of the longer distal end of the urethra, the neck of the bladder and the vascular-neural bundles. Use of intraurethral and intracorporeal administration of prostaglandins. As well as inhibitors of phosphodiesterase-5, are quite effective ways to treat impotence after radical prostatectomy.

As mentioned earlier, often after the completion of radical prostatectomy, the pathomorphological stage is higher than the clinical stage, which occurs in 30-40% of patients. In such patients, as a rule, the tumor progresses much faster. Moreover, in the study of 7,500 patients, it was found that the incidence of the surgical margin is 14 to 41%. In patients with a positive surgical margin and an undetectable PSA level, subsequent adjuvant treatment appears to be necessary.

In summary, radical prostatectomy certainly serves as an effective treatment for patients with localized prostate cancer, despite the fact that it is accompanied by some loss in quality of life.

Endoscopic radical prostatectomy

For the first time, laparoscopic radical prostatectomy was performed by WW Schuessler in 1990. French urologists presented an improved procedure for the operation. A Raboe, in 1997, developed an extraperitoneal endoscopic radical prostatectomy, and Bollens R. (2001) and Stolzenburg JU (2002) modified and perfected it. The advantages of endoscopic prostatectomy are small invasiveness, precision, less blood loss, a short period of hospitalization and rehabilitation. The shortcomings of this technique include the need for specialized equipment and tools, a long period of training for urologists.

Indications for endoscopic radical prostatectomy are the same as for retropubic prostatectomy, namely locally advanced prostate cancer in patients with an expected life expectancy of at least 10 years. Contraindications for her. As for other laparoscopic operations, are violations of the coagulating system of blood and pronounced changes in the function of external respiration and cardiac activity, common infectious diseases, purulent-inflammatory processes in the anterior abdominal wall. Relative contraindications include excess body weight, small and large volume of the prostate (less than 20 cm ² and more than 80 cm ⁵ ), neoadjuvant treatment, previous operations on the prostate (TUR, chrespuzyrnaya or retropubic adenomectomy). These factors make it difficult to isolate the prostate and contribute to the occurrence of intraoperative complications.

At present, there are still no remote oncological results of laparoscopic and endoscopic prostatectomy. However, preliminary results indicate an equal oncological efficacy of open and laparoscopic prostatectomy. Positive surgical margin is revealed depending on the stage of the disease in 11-50%. Overall and adjusted 5-year survival is 98.6 and 99.1%, 3-year recurrence-free survival is 90.5%.

[4], [5], [6], [7], [8], [9], [10], [11]

Alternative treatment of prostate cancer

The search for effective and safe methods of treating prostate cancer in the last decade remains one of the topical topics in urology. The most common modern minimally invasive methods of treatment of localized prostate cancer are brachytherapy, cryoablation, high-frequency focused ultrasound.

[12], [13], [14], [15], [16], [17]

Cryoablation

Cryoablation is the destruction of the prostate tissue by freezing. This is achieved by the destruction of cellular membranes by ice crystals, dehydration of tissues, and microcirculation disorders on the background of hypothermia. In existing systems, this ensures the circulation of argon in the needles introduced into the gland tissue. At the same time, it is necessary to heat the urethra to prevent necroticisation with a special catheter. The process is controlled by several sensors. The temperature in the gland tissue decreases to -40 ° C. Cryoablation is applicable for patients with localized forms of prostate cancer, a restriction on the volume of the prostate is 40 cm ³, with a larger volume of the gland it can overlap the pelvic bones, as with perineal brachytherapy. To reduce the volume of the prostate, preliminary hormonal treatment is possible. At the beginning of the first generation of systems for cryotherapy of prostate cancer, the simplicity of the method, the need for tissue irradiation, low traumatism and good tolerability caused the enthusiasm. However, with the accumulation of experience, the negative aspects of the method were discovered: a high risk of damage to the rectal wall with the formation of fistulas, impotence, the difficulty of monitoring the border of the "ice ball" around the probe, and urinary incontinence. Great hopes are attributed to the so-called third generation of cryosurgery plants using argon for cooling tissues and helium for their heating. They have a sophisticated temperature control system for tissues with several temperature sensors in the neck of the bladder and the external sphincter and visualization with rectal ultrasound in real time.

Indication for cryoablation is localized prostate cancer, especially in patients. Not interested in maintaining the potency or not having it at the time of treatment. It is possible to perform cryoablation in patients with small tumors that germinate the capsule, if there is a chance of getting into the freezing zone of the extrastrostatic part of the tumor. The volume of the gland more than 50 cm ³ can make it difficult to conduct the procedure due to the problematic one-stage adequate freezing of a large volume of tissue and interference from the pectoral articulation. In such cases, preliminary hormonal treatment is possible to reduce the volume of the prostate.
The evaluation of effectiveness depends on the success criteria used and the patient's risk group. With a PSA threshold of 0.5 ng / mL and 1 ng / mL, a 5-year disease-free period in a low-risk group (PSA less than 10, Gleason's score less than 6, stage less than T2a) reaches 60 and 76%, respectively.

[18], [19], [20], [21], [22], [23], [24], [25]

Highly focused ultrasound

Highly focused ultrasound also takes a definite place in the treatment of localized prostate cancer.

In addition to the primary treatment of cancer, high-fidelity ultrasound is used in the rescue therapy for local relapses after external radiation treatment. The method consists in the action of ultrasonic waves on the tissue. The increase in temperature of which leads to their lethal damage, the appearance of a foci of necrosis. The final effect is achieved due to the violation of lipid membranes and protein denaturation, as well as mechanical disruption of the normal structure of tissues during the formation of gas bubbles and cavitation. The last two moments create a technical problem of very accurate energy dosing. Because it makes it difficult to predict the precise boundaries of the necrosis foci. Its volume is small, so it is necessary to repeat the procedure repeatedly for the treatment of large areas of tissue. In the existing apparatus, ultrasound is used both for tissue destruction and for visualization, two crystals with different frequencies or one crystal with variable frequency are combined in the rectal head. During the procedure it is important to constantly monitor the position of the rectum wall to avoid damage to it. Use neoadjuvant hormonal treatment or TUR prostate before the procedure is possible to reduce its volume. The size is limited to 60 cm ². It is also possible to conduct two consecutive sessions, since after the first the size of the prostate is reduced. Highly focused ultrasound is a minimally invasive and safe procedure that does not require prolonged hospitalization. As a rule, a urethral catheter is left for a few days after the procedure.

Among the possible, although rare, complications, mention may be made of urethral rectal swine (1%), postoperative urinary retention in patients who have not undergone preliminary TURP, may require catheterization or epilepsy. Impotence occurs in every second patient. Urinary incontinence can be a consequence of the thermal damage to the external sphincter and takes place to varying degrees in 12% of patients.

Criteria for success were negative control biopsy, a decrease in the PSA level to a threshold value of 0.6 ng / ml (achieved after 3 months after the procedure) and the absence of growth dynamics during follow-up. At the moment, data for assessing long-term results is not enough. However, for patients with a low risk of a control biopsy at 6 months after treatment, a negative result occurs in 87% of the observations. In general, the technique is already widely used in many European countries, with the accumulation of experience, it finds its place in the treatment of prostate cancer.

Adjuvant treatment of prostate cancer (prostate cancer)

Adjuvant treatment of prostate cancer (prostate cancer) had a significant effect on the likelihood of recurrence and mortality in patients with localized breast cancer. Extrapolation of similar results to patients with prostate cancer is important for a positive surgical edge or not achieving the PSA level of a nadir. It is suggested that adjuvant treatment is effective in patients with a limited form of the disease, a positive surgical margin, a preoperative PSA level above 10 ng / ml. The Gleason sum is 7 or more. Possible options are anti-androgen monotherapy, monotherapy with luteinizing hormone-releasing hormone analogues (LHRH), and possibly finasteride. Adjuvant treatment with orchiectomy and radiotherapy in patients with stage T3N0M0 disease, who underwent radical prostatectomy, caused local and systemic progression of the process, no significant changes in the survival rate were observed. A large-scale placebo-controlled study with the inclusion of 8,000 patients is currently close to completing an assessment of the use of bicalutamide (150 mg / day) in the form of monotherapy after radical prostatectomy or radiation therapy in patients with limited prostate cancer. The main endpoints of the study are survival, time to progression, the cost of each "won" year of life.

Currently, there are results of the study of adjuvant treatment in patients with locally advanced disease after radiation therapy. A recent study by the European Organization for Research and Treatment of Bladder Cancer, involving 415 patients with locally advanced cancer, showed that the use of goserelin in the form of a depot just before the radiation therapy and for 3 years after it. Significantly improves local control and survival after 45 months of follow-up. Five-year survival rates with a Kaplan Meyer score are 79 and 62%, respectively, for the adjuvant "shoulder" of the study and the "shoulder" of patients receiving only radiation therapy (observation period 5 years). Adjuvant treatment is also effective for large tumors after radiation therapy (RTOG using depot form of goserelin).

Thus, adjuvant hormone therapy is a promising treatment method that is being tested in detail at the present time. Survival rates are objectively better after radiotherapy, the use after radical prostatectomy requires further study. The main criteria for the use of hormone adjuvant treatment is efficacy, good tolerability. Preservation of quality of life at a sufficient level (in particular, sexual function), a convenient mode of appointment and dosing.

[26], [27], [28], [29], [30], [31],

Conclusions

The stage of the tumor process, the age of the patient and the somatic status are of great importance in determining the tactics of treating localized prostate cancer. In patients with localized prostate cancer after the treatment, life expectancy does not differ from that in the population. Such positive results are a consequence of a number of factors:

• favorable latent course of cancer (in particular, diagnosed with
• identification and effective treatment of aggressive forms of the disease;
• rational use of hormonal treatment to prevent relapse.

With the advent of the era of population screening with the help of the definition of PSA, it is necessary to decide whether we really diagnose clinically significant prostate cancer and whether we are right for all such patients to perform radical prostatectomy - accessible information indicates that the majority of diagnosed malignant tumors are clinically significant. Despite this, screening is a controversial method; The American Cancer Association recommends using PSA screening in men over 50 years of age, while informing about its potential risks and benefits. In the US, the decline in morbidity and mortality from prostate cancer can be related specifically to screening (PSA + digital rectal examination). That is why there is an urgent need for additional randomized controlled trials of this issue.

At present, numerous studies have been done on the effectiveness of alternative therapies for patients with prostate cancer (radical prostatectomy, remote radiation therapy, active observation with delayed hormonal therapy).

For some patients, the potential benefit from the therapy is small. Therefore, treatment alternatives largely depend on the choice of the patient. Further analysis shows that for a specific group of patients (young age and with highly differentiated cancer of the gland) the choice is radical prostatectomy or radiotherapy. Active surveillance is suitable as an alternative for most people, especially with poor physical status. Nevertheless, the accuracy of the choice of treatment also depends on the impact on the patient's quality of life, additional research is needed in this area.

It is important to calculate the "cost-effectiveness" indicator, which must be carried out in terms of "won" years of life. Radical prostatectomy, so popular in many countries, is a relatively expensive alternative to treatment. In the US, its cost is 2 times higher than the cost of radiation therapy ($ 18,140 vs. $ 9,800). According to the calculations of insurance companies, about 60 000-70 000 radical prostatectomies are performed annually, their cost is high. The treatment of complications is also taken into account.

In general, no one can predict the tumor's tendency to progress, so most doctors are inclined to perform active surgical treatment, especially in patients under the age of 75 and with an expected life expectancy of more than 10 years. Time will tell whether it's justified or not.

On the other hand, in patients with a presumed life expectancy of less than 10 years, hormonal treatment and expectant management should be considered as an alternative. Antiandrogens play an increasingly important role in the therapy of early stages of the disease, and studies will confirm or disprove this position. When treating antiandrogens, the urologist needs to pay attention to such conditions as tolerance and dosing regimen to achieve compliance. Neoadjuvant treatment before radiotherapy is also justified, before routine treatment, its routine use is still limited by the lack of adequate information. Preliminary tests also undergo such methods as high-frequency interstitial radioablation of the tumor and focused ultrasound of high intensity. Of interest are cryotherapy, laser treatment with photodynamic enhancement and brachytherapy. Nevertheless, more research is needed on these alternatives.

Further research in this area affects the role of growth factors, oncogenes, tumor suppressor genes, apoptosis inducers.

[32], [33],