RU2471427C1 - Method of obtaining biopsy material for diagnostics of local cancer recurrence after radical prostatectomy - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine, namely to urology. In order to obtain biopsy material for diagnostics of local cancer recurrence after radical prostatectomy, sampling of material is performed by means of biopsy needle under control of transrectal ultrasound examination. Urethral catheter, which is visualised and used as landmark when biopsy needle punctures are performed, is preliminarily installed into urethra. Twelve samples are taken from adjacent to urethra zones of prostatic bed in specified succession. First, sampling is performed from neck of urinary bladder - two samples from each side relative to catheter, after that, from zone of vesicourethral anastomosis - one sample from each side of urethra, from zones of projection of vascular-nervous bundles - one sample from each, and from zone of external urethra sphincter - two samples.

EFFECT: method makes it possible to obtain biopsy material directly from prostatic bed.

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Description

The invention relates to medicine, namely to urology, to methods for producing biopsy material from the prostatic bed after radical prostatectomy and can be used to diagnose local relapse.

Despite the tendency in the past 10-15 years to improve the early diagnosis of prostate cancer and to identify more localized forms of the disease, to improve the surgical technique for performing radical prostatectomy, local recurrence after surgery remains an urgent problem.

This is primarily due to the insufficiently radical implementation of the operation. An early symptom of relapse is an increase in the prostatic specific antigen (PSA). An increase in PSA> 0.2 ng / ml after surgery is called biochemical relapse. Long-term biochemical recurrence (BR) of prostate cancer (PCa) is determined in 40% of patients undergoing radical prostatectomy (RPE), most of which (95%) in the first 5 years. PSA kinetics play a fundamental role in diagnosing the type of relapse and the rate of progression of prostate cancer. However, the PSA level does not provide complete and accurate information about the presence of relapse.

To select the optimal treatment tactic, it is necessary to determine its localization - local (local) or remote (systemic).

The use of pathomorphological data, such as Gleason's sum, damage to seminal vesicles, lymph nodes, positive surgical margin, as well as PSA kinetics plays a fundamental role in the diagnosis of localization of relapse and the rate of PCa progression.

According to most European researchers, the absence of confirmed local relapse is not a contraindication to salvage radiation therapy of the prostatic bed.

However, the authors agree on the significant advantage of the survival of patients with pathomorphologically proven local recurrence of prostate cancer. To date, the most reasonable PSA level, which is a criterion for BR, can be considered an indicator of 0.2 ng / ml, because the vast majority of patients (95%) with this indicator will have a progression of the disease within 3 years of observation.

Determining the localization of relapse due to the accurate diagnosis of the presence or absence of local relapse after RP is a key point, since further treatment of the patient depends on this and, as a consequence, cancer-specific survival (life expectancy).

There is a method of detecting local recurrence of prostate cancer after radical prostatectomy by determining a specific prostatic antigen followed by transrectal ultrasound and analysis of echotomographic images [B.A. Minko, M.I. Karelin, E.V. Evtushenko, M.I. Shkolnik , D.G. Prokhorov. Local recurrence of prostate cancer after radical prostatectomy. Transrectal ultrasound diagnostics. Oncourology No. 2, 2008, pp. 53-56].

Transrectal ultrasound (TRUS) is performed with a specific prostate antigen of 0.2 ng / ml or more. If the value of the specific prostatic antigen does not exceed 0.2 ng / ml, transrectal ultrasound is performed no later than 8 months after radical prostatectomy, and then at least 1 time in 3 months, performing it in the energy mapping mode with subsequent three-dimensional angiography. The analysis of echotomographic images is carried out with a sequential angular displacement of up to 360 ° in increments of 5-15, and if at least one of the obtained images is found, the pathological vascularization zone is judged on the initial signs of local recurrence.

The disadvantage of this method is that it does not always allow you to identify changes in the study area, indicating the presence of local recurrence. In addition, it is impossible to differentiate the revealed changes by the known method, to distinguish a benign postoperative scar from a pathologically altered tissue, i.e. local relapse. The information content of the method with PSA≤0.2 ng / ml is minimal, there is no histological confirmation, therefore, this method is currently not recommended for use in the absence of marker (PSA) relapse.

In this regard, a prostate bed biopsy is the best diagnostic method for diagnosing local recurrence of the disease, especially in patients with low PSA levels, as it allows you to get the most complete, accurate and voluminous information.

As the closest analogue, a method for obtaining biopsy material for the diagnosis of local recurrence after radical prostatectomy [Vincenzo Scattoni, Marco Roscigno, Marco Raber, Francesco Montorsi, Luigi Da Pozzo, Giorgio Guazzoni, Massimo Freschi, Patrizio Rigatti, MultipleVesico-Urethral Follower-following is adopted: The Predictive Roles of TRUS, DRE, PSA and the Pathological Stage. European Urology 44 (2003) 407-414], including sampling of material under the control of TRUS using an apparatus with a biplane sensor with a frequency of 6.5 MHz. Biopsy samples of the test tissue are produced only from the area of the vesicourethral anastomosis, not covering the bed of the removed prostate gland itself. Local anesthesia is not performed. A biopsy is performed under TRUS control using a biopsy needle with a diameter of 18G and a biopsy gun (Manan Pro-Mag 2.4).

In the absence of changes (with digital rectal examination (PRI) and TRUS), a six-point random biopsy is performed from the neck of the bladder: one injection is performed in front and behind the neck of the bladder, and the other injections are made on the side and back of the anastomosis.

In the presence of hypoechoic formations, directive injections and sampling from these areas are performed.

However, the known method has several disadvantages. According to the ultrasound image, it is almost impossible to visualize the urethra, and therefore there is a likelihood of taking a biopsy from the same side, the information received is incomplete.

The biopsy technique does not cover the prostatic bed itself, but only a small area of the neck of the bladder and the external sphincter of the urethra, as a result of which local recurrence in the absence of changes according to PRI and TRUS is only 28%. The lack of accurate informative data does not allow an objective diagnosis of the presence of local relapse, and therefore, to determine the localization of relapse and conduct adequate treatment.

The objective of the invention is to provide an evidence-based method for obtaining biopsy material for the diagnosis of local cancer recurrence after radical prostatectomy, which allows to obtain complete and objective information for adequate timely treatment.

The essence of the invention lies in the fact that in the method of obtaining biopsy material for the diagnosis of local cancer recurrence after radical prostatectomy, including sampling the material using a biopsy needle under the control of a transrectal ultrasound examination, a urethral catheter is first inserted into the urethra, which is visualized and used as a guide when injecting a biopsy needle, to obtain biopsy material, twelve samples are taken from the zones of their own but the prostatic bed adjacent to the urethra, in a certain sequence, with the first sample taken from the neck of the bladder on each side of the catheter in two samples, then from the zone of the vesicourethral anastomosis on each side of the urethra, one sample, from the zones projection of the neurovascular bundles - one sample and from the zone of the external sphincter of the urethra - two samples.

Using the invention allows to obtain the following technical result.

For the first time, a new, evidence-based method for obtaining biopsy material directly from the prostatic bed after radical prostatectomy was created, which makes it possible to make an accurate and timely diagnosis of the presence or absence of local relapse and to determine on this basis the form of its localization - local or remote.

Using the proposed method allows to obtain complete and objective information for the correct assessment of the structure of the prostatic bed and to identify local recurrence in its presence in almost 100% of cases.

The method makes it possible, on the basis of the data obtained, to develop an algorithm for further tactics, including the selection of timely and effective methods of treatment and assessment of the radicalism of the operation, which allows to increase cancer-specific survival.

The method is virtually painless.

The technical result is achieved due to the new technology for obtaining biopsy material developed by the authors, which provides for the determination of the localization of relapse after radical prostatectomy due to the accurate diagnosis of the presence or absence of local relapse.

The method is developed on the basis of clinical trials and statistical processing of the obtained material. The authors proceeded from the fact that the prostate gland is in close contact with the external sphincter of the urethra and the neck of the bladder. As studies have shown, the spread of the tumor occurs perineurally and perivascularly, it is in these places that the remaining cancer cells (the positive surgical margin) are localized. Based on this, the authors take samples from precisely these areas where a positive surgical edge is possible: the bladder neck, vesicourethral anastomosis, areas of the neurovascular bundles, the external sphincter - the urethra.

The authors worked out the maximum optimal number of samples necessary and sufficient to obtain complete information about the presence or absence of relapse - twelve, taking into account the fence on two sides of the urethra. As shown by tests of the method, the twelfth biopsy can be crucial for the objective diagnosis of local recurrence.

Performing more injections in a small and vital area can lead to unwanted complications.

The proposed sampling sequence is appropriate. When performing a biopsy, as a rule, anatomical structures are damaged, hematomas and tissue edema are formed. If you start sampling from the central zones, then the hematoma and edema spread in the cranial and caudal direction, which prevents the taking of subsequent samples.

In accordance with the technology developed by the authors, injections of the biopsy needle for sampling are carried out sequentially in descending order - from top to bottom along the urethra.

Pre-installation of the urethral catheter in the urethra with subsequent visualization allows you to use it as a guide for the location of the urethra when sampling.

The method is as follows.

In a patient after radical prostatectomy, blood PSA is determined every 3 months during the first year after surgery. In the next 3 years - every 6 months and then 1 time per year. When its value is more than 0.4 ng / ml in two consecutive changes, a biopsy is performed.

A Foley No. (Fr) 14-16 urethral catheter is pre-installed in the bladder through the urethra, which is visualized and used as a guide for the location of the urethra, for further implementation of the biopsy needle injections. The balloon of the catheter is inflated into 10 ml. The bladder is filled with saline in a volume of 200 ml. A biopsy is performed in a urological chair under the control of transrectal ultrasound using an automatic biopsy gun from BARD (USA) under the control of a rectal ultrasound probe with a frequency of 7.5 MHz. The tissue columns are taken from the prostatic bed using a Bard Magnum 18G automatic biopsy needle with a diameter of 1.2 mm and a tissue sampling depth of 18 mm. Intrarectal anesthesia with lidocaine gel is used.

To obtain biopsy material, twelve samples are taken from the zones of the prostatic bed proper adjacent to the urethra in a certain sequence. Initially, the material is taken from the neck of the bladder - two samples on each side relative to the catheter. Then, material is taken from the zone of the vesicourethral anastomosis on each side of the urethra, one sample from the zones of projection of the neurovascular bundles - one sample, and from the zone of the external sphincter of the urethra - two samples. Each biopsy obtained is placed in a separate container with a formalin solution of 10% and marked.

After confirming the recurrence of the disease, the patient is given radiation treatment or other methods of "local" treatment.

EXAMPLE 1. Patient M., 59 years old, I / B 52394, was admitted to the clinic of urology and surgical andrology GOU DPO RMAPO 12/07/2006, with a diagnosis of prostate cancer _with T _2c N _x M ₀ .

From the anamnesis: for 4 years was observed in the clinic at the place of residence regarding benign pancreatic hyperplasia. During the control examination in March 2006, the PSA level was 15.2 ng / ml, with PRI a focal area of compaction was found in the left lobe. A multifocal pancreatic biopsy performed under ultrasound guidance revealed pancreatic adenocarcinoma. The patient was sent to the clinic of urology and surgical andrology GOU DPO RMAPO.

Based on the examination (lung X-ray, pelvic CT, skeleton scintigraphy, general and clinical blood tests), the diagnosis was made of pancreatic cancer in stage T _2c N ₀ M ₀ .

On December 14, 2006, the patient underwent a radical post-discharge prostatectomy. Histology of the removed preparation: prostate adenocarcinoma with the exit of the capsule in a limited area ( _p T _3a N ₀ M ₀ ). The postoperative period was uneventful. December 24, 2006 (on the 10th day) after the operation, the patient was discharged from the clinic with a recommendation every 3 months to contact the clinic for a follow-up examination.

3 months after RPE (March 30, 2007), the PSA level was 0.1 ng / ml. The patient was asked to come for examination in June - July 2007. During the first 2 years, the PSA values were less than 0.1 ng / ml. In the third year after the operation, a progressive increase in PSA to 0.6 ng / ml was noted. The patient underwent PRI, TRUS, X-ray of the lungs, CT, MRI of the pelvis, skeleton scintigraphy, according to which no pathological lesions were found in the operation zone or in other organs.

34 months after the RPE (10/29/2009) a biopsy of the prostatic bed was performed from 12 points according to the proposed method. A Foley No. (Fr) 14-16 urethral catheter is pre-installed in the bladder along the urethra, which is visualized and used as a guide for the location of the urethra in the subsequent implementation of biopsy needle injections. The bladder was filled with saline in a volume of 200 ml. The biopsy was performed in a urological chair using an automatic biopsy gun from BARD (USA) under the control of a rectal ultrasound probe with a frequency of 7.5 MHz. Intrarectal anesthesia with lidocaine gel was used. To obtain biopsy material, twelve samples were taken from the zones of the prostatic bed proper adjacent to the urethra in a certain sequence. First, the sample was taken from the neck of the bladder on the left and right sides of the catheter in two samples, then from the zone of the vesicourethral anastomosis on each side of the urethra, one sample, from the projection zones of the neurovascular bundles - one sample and from the zone external urethral sphincter - two samples. Each biopsy sample is placed in a separate container with 10% formalin solution and labeled.

Conclusion: fragments of fibro-muscular tissue, in two of which (1, 10) foci of acinar adenocarcinoma with perineural invasion.

Thus, after 34 months of the patient, a local recurrence was detected, although neither a manual examination, nor a PSA level, nor a two-dimensional seroscale TRUS, CT, MRI showed yet its development.

The patient received a course of rescue external radiation therapy (NLT) in a dose (SOD 74 Gy). 12 months after NLT, PSA figures are 0.01 ng / ml, there is no progression of prostate cancer.

The method is developed on the basis of clinical trials and statistical processing of the material.

Based on the fact that the possibility of accessible visualizing research methods is limited at low PSA numbers, and the effectiveness of existing methods for obtaining biopsy material is low, the task was to investigate the possibility of detecting local recurrence in the anastomosis after RP by random biopsy according to the scheme proposed by the authors. To this end, in a clinic of urology and surgical andrology GOU DPO RMAPO 43 patients underwent transrectal multifocal prostate bed biopsy for biochemical recurrence after radical prostatectomy. A biopsy of the prostatic bed was performed according to the above scheme. Before biopsy, all patients underwent PRI, TRUS, CT, MRI, osteoscintigraphy, according to which the source of relapse could not be established.

The median age of the patients was 64.7 +/- 6.6 years (53-78). The median PSA before prostate bed biopsy was 0.9 ng / ml (0.2–20). Tumor tissue of the prostate - 40% (17/43 patients). Adenomatous and normal prostate tissue - 11.6% (5/43). The combination is 7.0% (3/43). Zones of detection of tumor tissue. Bladder neck - 24% (4/17). Sphincter area - 35% (6/17). The combination of the neck of the MP + sphincter 41% (7/17). The substrate for the growth of PSA (prostate cancer, BPH, normal prostate tissue, seminal vesicles) = 58% (25/43). Pathological anatomical stages (TNM) in the group of patients with negative biopsy of a vesicourethral anastomosis: _p T _2a - 8%, _p T _2b - 4%, _p T2 _c - 34%, _p T _3a - 19%, _p T _3b - 31%, _p N ₁ - 26.9%, positive surgical margin - 11.53%. And in the group of patients with positive results: _p T _2a - 7%, _p T _2c - 31%), _p T _3a - 25%, _p T _3b - 31%), _p N ₁ - 11.76% positive margin - 35 , 29%.

Morphological studies of the material obtained by biopsy of the pancreas were performed in the pathology department of the Moscow Research Institute of Oncology named after P.A. Herzen.

After a biopsy, not a single case of urinary retention, a single infectious complication, moderate hematuria, termination of 2-3 days was detected.

This fact made it possible to establish that a biopsy of the prostatic bed according to the proposed scheme reveals a local recurrence of almost 100%, if any. It is a safe manipulation and is indicated for specially selected patients with biochemical relapse in the absence of metastases according to imaging research methods.

After RPE in 17 patients, local relapses have been identified to date, all of them are timely directed to treatment. The remaining patients continue to be observed.

Thus, the proposed method, compared with the known ones, has a significant advantage in that it provides early and accurate detection of local recurrence of PCa, which is not allowed by finger examination, PSA level, or TRUS in the standard seroscale mode, CT, MRI, PET, nor previously proposed biopsy schemes.

Claims (1)

A method of obtaining biopsy material for the diagnosis of local cancer recurrence after radical prostatectomy, including sampling the material using a biopsy needle under the control of a transrectal ultrasound, characterized in that an urethral catheter is first inserted into the urethra, which is visualized and used as a guideline for biopsy needles, to obtain biopsy material, twelve samples are taken from areas of the prostatic of the ridge adjacent to the urethra in a certain sequence, with the first sampling of the material being made from the neck of the bladder on each side of the catheter in two samples, then from the zone of the vesicourethral anastomosis on each side of the urethra, one sample, from the zones of projection of the vascular nerve bundles - one sample and from the zone of the external sphincter of the urethra - two samples.