TRANSRECTAL ULTRASOUND-GUIDED PERCUTANEOUS
CRYOSURGICAL ABLATION OF THE PROSTATE (CSAP) FOR PROSTATE CANCER
(PC): RUSSIAN EXPERIENCE
Georg Prochorov, Vladimir Murashov, *Michail Karelin,
Dept. of Urology, Clinical Hospital of Russian Academy of Sciences, Saint Petersburg; *Dept. of
Oncourology, Central Research of Roentgenology and Radiology, Saint Petersburg; **Dept. of
Radiology, Mandryka Central Hospital, Moscow, Russia
Abstract. Modern technique of CSAP includes wide experience for radical treatment of
local confirmed PC. We have attempted to investigate the safety and efficiency of TRUS- guided
CSAP also in cases of local-advanced form as well as advanced prostate cancer.
A non- randomized prospective study was undertaken in two groups. The first 17 patients
(pats) with local and local-advanced stages (T1-3N0-1M0) of PC received a radical cryoablation
with two freeze cycles (Spembly Cryosurgical System -LCS 3000, Candela, Inc. USA). The
other 4 patients with advanced stage (T4N1-2M1) of PC have been treated additionally with
systemic chemo-gormone-immunotherapy. Chemo-hormonal therapy contained the maximal
androgen ablation and use of Estracyt (Upjoin&Pharmacia) in high doses. The scheme of
immunotherapy included systemic and intratumor injection of human recombinant IL-1b
(Research Institute of High Pure Bioproducts, St.Petersburg). All cases have closed follow- up 6
months post treatment.
15 pats in first group are biopsy negative. 1 pat. had a residual tumor in the prostate apex
and underwent repeated cryoablation with good result at the nearest follow- up. 1 pat. in second
group have had complete regression, 2 pats- partial regression and in 1 pat. the pain palliation has
been noted. Three patients has developed urinary stress-incontinence after self-removing of
Our first experience of CSAP shows early promise not only for organ-confined forms of
PC but for advanced forms.
Introduction & Objectivities. CSAP has gained popularity as alternative treatment for
localized prostate cancer with excellent local tumour control. Advantages of the technique
include local effectiveness in eradicating tumours, minimal morbidity rate and lower costs when
compared to radical surgery.
Materials & Methods. Between July 1997 and November 1998, 21 pats underwent
prostate cryosurgery. The mean age of the patients was 64 years(range, 47-84 years).
All patients had prostate carcinoma diagnosed and staged by transrectal ultrasound-
guided biopsies in which the sextant approach was used. As part of the initial staging workup, all
patients had a chest X-ray and bone scan. Many of the patients underwent computer tomography
and magnetic resonance imaging of abdomen and pelvis.
The median Gleason score (combined Gleason tumor grade) for all patients was 5; the
majority of the patients had a score < 7. Five of the 21 pats had clinical Stage II (TNM system)
disease preoperatively, whereas 12 pats had Stage III (first group) and 4 pats-IV (second group).
Seven pats had had previous surgical procedures performed for benign prostate diseases. Seven
patients had had previous radiation therapy for prostate carcinoma, but the treatment had failed.
Cryosurgery Procedure. All procedures were performed with the Spembly Cryosurgical
System- LCS 3 000 ( Candela, Inc. Boston, USA). The Aloka 630 ultrasound scanner (Aloka,
Japan), with a biplane probe (transaxial sector 5 MHz and linear 7.5 MHz), was used to guide
the cryogenic probe placement and to monitor the freezing process for all patients.
We used the same mapping technique as Lee et al. for probe placement (Fig. 1).
We currently use a combination of transrectal ultrasound and thermocouple temperature
monitoring to determine the end point of the cryosurgical procedure. The target fatal temperature
that we try to achieve in all thermocouple positions is below -20 °C. Our current technique is to
perform a double freeze, a freeze plus a pullback by gland length, with a target temperature of -
20 °C for each freeze cycle. We used a urethral standard warming catheter by Morris supplied by
Additionally for prevention of complications we have introduced a specially designed
solution, which has been prepared ex tempere and consisted of proteolytic,corticosteroid,
antibiotic and cryoprotector. For preservation of sphincter urethra externum and rectum we
usually injected this warm cocktail percutaneously into anterior preprostatic space (Retzii
cavum) and retroprostatic rim (Fig.2).
In an ongoing pilot study of 2nd group the standard palliative (single freezing) CSAP was
carried out in cases of advanced (T4N1-3M1) PC.
The regime of proposed immunotherapy was as follows (Fig.3):
rec.IL-1b (betaleukin), in dose of 5ng/kg subcutaneously daily during 3-5 days with 1-2
days interval of resting before CSAP .
According to our hypothesis in order to enhance the tumor destruction, we are proposing
to inject rec. IL-1b (up to 10 ng) into tumour also followed 24 hours later by cryosurgery .
The initial immunological status and its consequent alterations will be evaluated by
studies of systemic and local immunity under special protocol.
Follow-up included routine clinical investigation, prostatic specific antigen (PSA), X-rays
and scintigraphy of sceleton, computer tomography and magnetic nuclear resonance imaging of
abdominal and pelvic cavity, thorough immunomonitoring.
Results. The patients were hospitalized for 4-7 days, with a mean stay of 5.3 days. Most
pats were able to return to their normal activities 3-4 weeks after the procedure.
Complications. The major complications of cryosurgery included sloughing (necrosis) of
the prostatic urethra- 7 pats, bladder neck contracture -3 pats, incontinence- 3 pats, and
impotence- 17 pats.
PSA and Biopsy Results. The median PSA levels of the 1st group consistently remained
below 0.5 ng/mL after cryosurgery, with a range of 0.05-12.2 ng/mL. Sixteen of 17 patients from
1st group had follow-up prostate biopsies. 15 patients in first group are biopsy negative. 1 pat.
had a residual tumour in the prostate apex and underwent repeated cryoablation with good result
at the nearest follow up.
1 pat. in second group had complete regression, 2 pats- partial regression and in 1 pat. the
pain palliation was noted. In the first 3 cases we investigated mainly the clinical remission of
metastatic lesions, biochemical significant failure of PSA (from 83 to125 ng/ml initially to 15-
45 subsequently), improvement of quality of life, indirect indications of enhanced tumor-specific
immunity (increase of quantitative parameters of antigen activation- CD25,HLA-2, total
lymphocytes, cytotoxic lymphocyts and natural killers; enhancement of functional activity of
lymphocytes, stimulation of IL-2, IL-8 etc.). Remarkably, in these cases we confirmed formation
of a tissue destruction zone at the site of intratumoural injection of IL-1b (Fig.4).
Conclusion. Our first experience of CSAP shows early promise not for organ-confined
forms of PC but for advanced PC especially with the use of guided cryoimmunotherapy.
The findings of 1st group have confirmed the high success rates (in 15 of 16 pats -
negative biopsy) in the nearest follow-up of CSAP for different forms of PC.
Our initial results of pilot-study of 2nd group are encouraging in connection with possible
efficiency of this therapeutic modality for advanced prostate cancer. In comparison with previous
studies, tumor-specific immunity may be enhanced not by subsequent cryotherapy, but by
repeated systemic immunotherapy by recombinant interleucin-1-b. But to prove this conjecture,
more investigations are needed.
Fig. 1. A planning map for cryoablation is shown (a) A transverse view, near the mid-
gland of the prostate, is shown. Cryogenic probes depicted by are numbered 1-5. Attempts were
made to keep the distances between the probes less than 1.8 cm. Probes 1 and 4 are placed in a
way that allows distance y to exceed distance x. Thermocouple positions are depicted as open
circles. Anterior thermocouple (An) is placed in the anterior fibromuscular stroma. Apex
thermocouple (Ap) is imbedded 1 cm within the substance of the prostate in between Probes 4
and 5. The neurovascular thermocouples (R and L) are placed in the posterolateral margins of the
mid-gland. (b) A longitudinal view through the midline of the gland is shown. Denonvilliers'
thermocouple (D) is placed in between the rectum and the posterior portion of the prostate gland.
Probe 5 is placed closer to the prostatic urethra than to the rectum. UW: urethral warming
Fig.2. TRUS during CSAP demonstrating the protection of closest organs around iceball:
the injected cocktail into anterior and posterior paraprostatic spaces.
Fig.3. The pathways of stimulation (+) and suppression (-) of immune-mediated
cryoablation by our concept of guided cryoimmunotherapy.
Fig.4. TRUS of advanced PC- 3 months after intratumoral injection of rec.IL-1b: UR-
urethral diverticula in the site of destructive tumour node