Minimally invasive treatment of kidney cancer prostate cancer —- way to go
In the past 50 years, due to the development of imaging technology, the incidence of small renal cell carcinoma, i.e., kidney cancer less than 100 px in diameter, has increased by a factor of 1, and its incidence rate in total kidney cancer has increased year by year, and 20% of kidney tumors less than 100 px in diameter are benign tumors [1]. At the same time, the incidence of systemic metabolic diseases has increased significantly for renal tumor resection with reduced renal function, and preserved kidney surgery is of increasing concern. Especially for the elderly, who are at greater perioperative risk, minimally invasive ablative procedures such as cryotherapy or radiofrequency ablation therapy can be an option.
The aim of minimally invasive treatment for kidney cancer is to preserve as much normal kidney tissue as possible and minimize complications. Radiofrequency ablation and cryotherapy are the most studied modalities [2], and these two minimally invasive treatment techniques are discussed in this paper.
In 1997, Zlotta et al [3] first reported the treatment of renal tumors located in the periphery by percutaneous radiofrequency ablation one week before radical nephrectomy, and in 1999 another study was performed in animal trials. In the same year, McGovern et al [4] successfully performed radiofrequency ablation under ultrasound guidance in a patient with a renal tumor who refused surgery. Most investigators have used radiofrequency ablation therapy technique as a palliative procedure for patients with renal cancer who are inoperable or cannot tolerate surgery, or who refuse surgery.
The 2011 NCCN guidelines for the treatment of kidney cancer state that active surveillance or ablative therapy can be chosen for stage T1 kidney tumors that cannot tolerate surgery, and the risk of local recurrence of tumors after thermal ablation therapy is higher than that of conventional surgery. And in the 2011 EAU guidelines for the treatment of kidney cancer, percutaneous minimally invasive ablation technique, as a category 2b evidence for kidney tumor treatment. Its advantages include reduced perioperative complications, no need for hospital admission, and the ability to reduce the risk of surgery in high-risk patients. Indications are small, elderly patients with occasional renal cortical disease, patients with a high susceptibility to tumors, bilateral renal tumors, and patients with the potential for renal failure after isolated nephrectomy. Absolute contraindications include coagulation disorders, critically ill patients, etc.
Technical Information
1.Principle of radiofrequency ablation The high frequency alternating current with frequency of 460~500 KHz is used to destroy the tumor cells through the radiofrequency generator of 150~200 W and the needle-shaped radiofrequency ablation electrode connected with it, which is inserted into the target tissues and generates heat energy at the rear tip. The dispersion electrode applied to the patient’s thigh forms a current circuit with the ablation electrode. The cells of living tissues can die within minutes at 49 ℃, and over 60 ℃ can cause cell protein denaturation, loss of enzyme function, cell membrane lysis and cytoplasmic destruction leading to irreversible death. There are monopolar and multipolar electrodes. The range of tumor treated by monopolar RF ablation needle at one time is small, while multipolar electrode needle expands into umbrella shape, oval shape, etc., which increases the treatment range. The practicality of percutaneous radiofrequency ablation under the guidance of imaging equipment is strong, and this method is also feasible for those with poor kidney function.
2.The principle of cryoablation Cryoablation is the earliest temperature treatment method in clinical application, and it is widely used. Liquid nitrogen or argon gas makes the local temperature drop rapidly to -20 ℃ or below, through the three processes of low temperature, freezing and thermal thawing to make the cells denatured, disintegrate and die. The mechanism of cryoablation includes: (1) the temperature in the tissue drops to -50~-60 ℃, and the ice crystals formed inside the cells can directly lead to cell death through mechanical damage; (2) the ice crystals formed inside the cell interstitial space
crystals, so that the extracellular fluid is concentrated, cells are dehydrated and crumpled; (3) the electrolyte concentration of intracellular fluid increases, and the enzyme activity decreases prompting cytotoxic damage; (4) after tissue freezing, small blood vessels contract, capillaries are rapidly occluded, microcirculation stops, and cells die due to ischemia (5) after cryosurgery, cells are fragmented and tumor antigens are released, triggering subsequent immune responses. Because tumor margins are easily survived, it is often necessary to freeze normal tissues more than 1 cm around them to prevent tumor cells from surviving. Several freezing and thawing procedures are more effective than one freezing treatment.
Imaging localization
There are no large clinical trials comparing the use of ultrasound, CT and MRI for ablation, and each modality has its advantages and disadvantages. Ultrasound has the advantage of real-time tumor surveillance, but ultrasound is more operator-dependent and subject to more interfering factors, such as oversized patients and bowel distention. CT is less subject to interference, but image quality may be compromised. Enhanced CT allows differentiation of coagulated necrotic tumor from normal tissue, while MRI uses soft tissue as a contrast to localize the tumor by different sequences of images. Fast T1-weighted image T2 sequence not only enables real-time localization, but also real-time monitoring of post-ablation efficacy.
For cryoablation treatment, due to the difference in temperature at various points within the tumor, the freezing range must include 5 mm of normal renal tissue outside the tumor in order to ensure adequate cutting edge. Since ice crystals may produce acoustic shadowing after freezing, ultrasound cannot clarify its boundary, and with the help of CT, other tissue side damage can be avoided, while MRI can see this density-diminishing band through the T1-weighted signal change and clarify the cutting edge after ablation .
Surgical modalities
Both radiofrequency ablation and cryotherapy can be performed either percutaneously or laparoscopically. In the past, radiofrequency ablation was mostly performed in a percutaneous manner, while cryotherapy was mostly performed in the latter. With the advancement of microtubularization technology, cryotherapy is gradually transitioning to a percutaneous approach. In general, tumors on the ventral flank of the kidney are not suitable for the percutaneous approach, but this is not a contraindication to the decision.
Finley [5] compared the efficacy of percutaneous and laparoscopic cryotherapy for renal cancer and showed that both the operative time and the hospital stay were prolonged in the latter compared to the percutaneous approach. The percutaneous approach used fewer probes, shorter anesthesia, shorter hospital stay, faster recovery, and fewer surgical complications (3% & 7%). Radiofrequency ablation presents similar characteristics.
Laparoscopic procedures are more invasive than the percutaneous route, but have the advantage of more complete treatment because they are performed under direct vision. The need for retreatment after laparoscopic and percutaneous treatment has been reported to be 5.1% and 27.5%, respectively.
Anatomical and oncological factors
A multifactorial analysis by Gervais et al [6] of 100 patients who underwent percutaneous renal puncture found that tumor size and location were independent predictors of RF ablation. Tumor size (<3 cm) and tumor location (peripheral type) were found to be easier to treat for renal cell carcinoma located laterally and posteriorly than for those located medially and anteriorly.
For renal cell carcinoma <3 cm, the complete necrosis rate is up to 100%, for 3-5 cm tumors the necrosis rate is about 93%, and for >5 cm the necrosis rate is about 28%.
The cooling effect of intravascular blood flow and the electrical resistance of tissues can affect the therapeutic range of radiofrequency ablation. Radiofrequency ablation of ischemic and nonvascular tissues can increase the therapeutic range. The efficacy of radiofrequency treatment can be increased after embolization of the vessels.
Because of the insulation of perirenal fat and the heat dissipation of large blood vessels, peripheral renal cancer often shows complete necrosis. Unlike central renal carcinoma, overheating leads to damage to the collecting system and the large vessels of the renal sinus. Special attention is paid to the kidney and surrounding fragile tissues such as the ureter, genitofemoral and ilioinguinal nerves, psoas major, small intestine and ileum, and adrenal glands.
Physical factors
The kidney is a highly perfused organ, with four times more perfusion than the liver, a feature that determines the way it dissipates heat and the difference in energy loss. Due to the perfusion of the large vessels, the “thermal ablation” effect may diminish the energy available for tumor treatment. Therefore, for highly perfused renal tumors, consider increasing the number of ablations or slowing down the rate of temperature reduction after RF ablation. The percentage of tumor recurrence requiring reablation is relatively high after radiofrequency ablation compared to cryotherapy.
Tumor characteristics and patient selection
Preoperative CT or MRI examination determines the clinical stage of the tumor. To achieve radical effect, the tumor is usually T1-T3a or Robson classification stage I or II. For advanced renal cancer, ablation techniques can be applied to treat the tumor locally or to relieve pain and hematuria symptoms.
For cystic kidney cancer, there are fewer studies, and Park et al [7] scholars applied radiofrequency ablation to treat 9 patients with Bosniak grade III to IV, and no recurrence was seen at 8 months of follow-up. It is now generally considered more appropriate for cystic kidney cancer with small tumors (<75px< span="">).
Complications
The safety profile of radiofrequency ablation for renal cell carcinoma is at least equivalent to that of partial nephrectomy. Complications include renal function impairment and operation-related complications. Hegarty et al [8] studied 82 patients with renal cell carcinoma treated with percutaneous radiofrequency ablation and showed no change in renal function at 2-year follow-up. The treatment of isolated kidney is equally safe.
Major complications refer to the need for clinical treatment without which complications such as permanent adverse effects or necrosis may occur, including hemorrhage, ureteral injury, urinary fistula, colonic injury, renal-enteric fistula, and severe pneumothorax [9]. The incidence of major bleeding (requiring blood transfusion) due to radiofrequency ablation is 0-2% [10-11]. Secondary complications can be largely treated conservatively and include mainly pain, small amounts of bleeding/hematuria, postoperative urinary tract infection, wound infection, neuromuscular injury and mildly elevated blood creatinine. Overall, the incidence of major complications is much lower than the incidence of minor complications. The distance of the tumor from the surrounding organs was strongly correlated with the complication rate, as well as with the operator’s experience. A multicenter study showed that the incidence of major complications of percutaneous radiofrequency ablation of small renal cell carcinoma was 11%, and half of the complications occurred in the early 1/3 of operations, suggesting an association with the learning curve [12].
Pre-ablation pathology
In the past, most scholars believed that percutaneous renal mass puncture had problems such as sampling errors and false positives, and even if the puncture results were accurate, the tumors were mostly early-stage tumors, and most of them did not need adjuvant therapy after surgery, so the pathological diagnosis of percutaneous renal mass puncture was not significant. However, with the wide application of ablation techniques, definitive pathological diagnosis is especially important for judging its efficacy. Previous studies only judged the efficacy of minimally invasive treatment from imaging diagnosed renal tumors, and since some of them are benign vascular smooth muscle lipomas, their efficacy may be overestimated or there is overtreatment. Some scholars have suggested that puncture biopsy should be performed for renal tumors [1], and the results showed that 37% of patients had benign puncture results. Therefore, it is recommended that puncture for pathology before minimally invasive treatment, which is important for the diagnosis and subsequent follow-up treatment of patients
Efficacy assessment
The efficacy of radiofrequency ablation is closely related to tumor size and location, and studies have shown that factors affecting complete tumor coagulation necrosis in a single treatment include tumor size (≤3 cm) and tumor location (peripheral type), and renal cell carcinoma located laterally and posteriorly is easier to treat than those located medially and anteriorly.Zagoria et al [13] performed radiofrequency ablation on 125 0.6 to 8.8 cm renal Among them, 116 renal cell carcinomas were completely ablated, 95 tumors with diameters <3.7 cm were completely ablated, 21 tumors with diameters >3.7 cm were partially necrotic in 30 cases, and 9 cases were found to have residual tumors during follow-up. For renal cell carcinoma with stage T1a tumors <4 cm in diameter, the 1- and 2-year tumor-free survival rates of radiofrequency ablation were similar to or significantly better than those of partial nephrectomy cases.Stern et al [14] randomized radiofrequency ablation to partial nephrectomy (for stage T1a renal cell carcinoma), and the 3-year tumor-free survival rates of radiofrequency ablation and partial nephrectomy were 93.4% and 95.8%, respectively. Hakime et al [16] demonstrated in nude mice that RF ablation combined with the anti-angiogenic drug sorafenib was effective in reducing microvessel density and expanding the area of RF-induced coagulative necrosis.Arima et al [17] reported on 31 patients with T1N0M0 renal cell carcinoma treated with stage 2 RF ablation, 29 of whom underwent arterial 6 d after embolization of the tumor vessels, with a 100% local control rate at 2-year follow-up (including one patient with tumor diameter >4 cm who recurred and was treated with radiofrequency). Zagoria et al [18] reported the efficacy of cryoablation in 320 cases of renal cell carcinoma with a tumor diameter of 2.3-2.6 cm, with a survival rate of 97%-100% during a follow-up period of 5.9-72.0 months. Another review reported 326 cases with a follow-up of 30.8 months and a tumor recurrence rate of 4.6% and a complication rate of 10.6%. Cryoablation is more effective than radiofrequency ablation for larger renal cell carcinoma. Since the clinical application of radiofrequency ablation for kidney cancer is later than that of cryoablation, further study is needed.
Radiofrequency and cryoablation study of prostate gland
Prostate cancer, as a common malignant tumor in the elderly, has become a threat to human life. Although the incidence of prostate cancer in China is much lower than that in Europe and the United States, the detection rate of prostate cancer has increased significantly with the increase of average life expectancy and the improvement of diagnostic techniques, especially the widespread use of prostate-specific antigen (PSA) testing. There are several treatment options for prostate cancer, including surgery, endocrine therapy, radiation therapy, etc.
There are several treatments for prostate cancer, including surgery, endocrine therapy, radiation therapy, etc. For the treatment of limited prostate cancer, radical surgery and active surveillance are currently the main clinical treatments. However, radical surgery is more traumatic, brings more complications, affects the quality of life, and because prostate cancer patients are older, they have more chances of combining other age-related diseases. The increase in pathological staging of prostate cancer after active surveillance leads to reluctance to use active surveillance in prostate cancer patients. The advent of radiofrequency ablation therapy for prostate cancer has adapted to the needs of this group of patients.
The use of radiofrequency ablation on the prostate can be traced back to the early 1990s and first began with studies on prostate enlargement [19].Djavan et al [20] and Zlotta et al [21] first reported the application of radiofrequency ablation for the treatment of prostate cancer. The procedure can be performed under general anesthesia, lumbar anesthesia or local anesthesia with the patient in a lithotomy position. A three-lumen catheter is applied to cool the urethra by instilling saline. A single electrode with a triple-hooked needle is inserted under transrectal ultrasound guidance through the
The perineum is inserted into the prostate, which creates a predictable spherical coagulation foci. Each barb needle has a
thermocouple that controls the temperature within the tissue to reach and maintain the desired level. The aim of the treatment is that each sub-needle
reach 100°C within 2-3 min and maintain this temperature level for up to 3 min. Djavan et al [22] did a correlation study between MRI and histopathology of 21 prostate radiofrequency ablation foci and concluded that radiofrequency ablation is a safe and feasible method with predictable lesion size and location. MRI observations of ablation foci correlated well with histopathology of coagulative necrotic foci. zlotta et al [23] performed a histopathological study of 15 patients proposed for radical prostatectomy to evaluate the safety and feasibility of radiofrequency ablation. The procedure was well tolerated and no complications were reported. Subsequently, many domestic and foreign scholars have conducted basic and clinical studies on ultrasound-guided trans-perineal pathway radiofrequency ablation for the treatment of prostate cancer. The results of the study concluded that radiofrequency ablation can effectively treat limited prostate cancer, with a reduction in prostate volume, a significant decrease in PSA, and coagulative necrosis in the ablated area of the puncture biopsy pathology after ablation. These manifestations are related to the size of the ablation focus, the degree of inactivation of the prostate cancer focus, tumor stage, follow-up time, and the presence or absence of concomitant endocrine therapy and radiotherapy [24-26]. the PSA decrease value is closely related to the extent of ablation, bilateral ablation is better than unilateral ablation, and unilateral overall ablation is better than unilateral regional ablation. However, PSA rebound occurs in cases above stage B. If transrectal color flow ultrasound and/or gray-scale real-time ultrasound harmonic imaging does not show significant abnormalities, close follow-up observation can be made. If the dynamic observation is gradually and significantly elevated to find the cause, if there is a local abnormality in the enhanced imaging can be considered repeated ablation therapy or with other therapies [27].
From the existing experience, ultrasound-guided radiofrequency ablation of prostate cancer is mainly suitable for patients with limited prostate cancer; or patients with contraindications to surgery and those who cannot tolerate surgery; and those who have failed endocrine or radiotherapy treatment. However, unlike radiofrequency ablation for other parenchymal tumors, radiofrequency ablation for prostate cancer is still in the exploratory stage after more than a decade of development and has not been widely used in clinical practice. The reasons that restrict its clinical application in prostate cancer may be as follows:
(1) The anatomy of the prostate gland is special, and the process of radiofrequency ablation is likely to cause thermal damage to the anterior peripheral structures, resulting in serious postoperative complications. (2) The multifocal nature [28-29] and diversity of prostate cancer increase the difficulty of treatment surgery and efficacy evaluation. Currently, ablation and systemic treatment of the entire gland are needed to achieve better outcomes. (3) Patients with prostate cancer are often combined with prostate hyperplasia, and some of them have a significant increase in prostate volume and morphological disorders, resulting in an increase in the number of needle placement points and increasing the difficulty of overlapping needle placement. (4) Although radiofrequency ablation coagulation foci can be predicted, the size and morphology of ablation foci are affected by many factors such as blood perfusion, resulting in uneven distribution of heat in the target area, which can easily cause incomplete treatment. (5) The current state of the art is that no radiofrequency ablation electrode has been developed specifically for the prostate, and the thermal field study of radiofrequency ablation of the prostate and the conformal ablation of specific forms of the prostate have not been studied in depth. Currently, electrodes with spherical or ellipsoidal coagulation foci are often used to treat the prostate, and such electrodes limit the application of RF ablation in the prostate, both in terms of the technical difficulty of overlapping needle placement and in terms of surgical safety.
Cryotherapy for prostate cancer also began in the 1990s, with the prostate site reaching <-40 °C, while surrounding tissues such as the external rectal sphincter were kept warm to avoid damage. Initially, a 3-mm diameter probe was used, and as the technology improved, a 1.5-mm, or 17 G, probe was gradually adopted. Cryotherapy has to achieve two things: 1, induction of cell death, including freezing rupture, necrosis and apoptosis. 2, maximum cell killing, involving freezing rate, target temperature, freezing time, rewarming time, number of freezing cycles, etc.
Currently, for low- to intermediate-risk limited prostate cancer, the size of the prostate is also an important factor. For oversized prostates, neoadjuvant therapy such as endocrine therapy may be considered, but the results are unclear.
For patients with PSA >20ng/ml or GS score 8 to 10, there is an increased risk of pelvic lymph node metastasis, therefore patients with a probability of lymph node metastasis of 25% or more as determined by nomograms or other established predictive methods are advised to have their pelvic lymph nodes clarified for metastasis prior to cryotherapy. Cryotherapy is not recommended in patients with previous TURP surgery, as it can lead to an increased risk of urethral necrosis, difficulty in warming the mucosa, and consequently, increased risk of carrion formation and urinary retention. Therefore, cryotherapy is generally recommended for patients with PSA <10 ng/ml. Cryotherapy can be used for patients with a Gleason score of 7 to 8, PSA >10 ng/ml but <20 ng/ml, or clinical stage T1b.
The efficacy of cryotherapy is diagnosed using monitoring of PSA changes and pathology on post-ablation puncture biopsy. There is a lack of consistent labeling of biochemical recurrence because the urethra is preserved and therefore PSA may not fall to very low levels after cryotherapy, but the lower the trough of PSA, the lower the likelihood of a negative post-operative prostate biopsy and the longer the PSA stabilization time. It has been reported in the literature [31-33] that the five-year risk of biochemical recurrence of low-, medium- and high-risk prostate cancer ranges from 65% to 92%, 69-89% and 48-89%, respectively. According to ASTRO criteria i.e. three consecutive elevations of PSA, the 5-year disease-free recurrence rate was 85% for low-risk patients and 73.4% and 75% for intermediate and high-risk, respectively. In contrast, applying the Phoenix criteria, i.e., PSA nadir plus 2, the 5-year biochemical recurrence-free rates were 91%, 78%, and 62% for low-risk, intermediate-risk, and high-risk, respectively. A number of other long-term follow-up outcomes, such as metastasis status, and disease-specific survival time, are missing and therefore cannot yet be compared with the outcomes of radical prostate cancer surgery with radiotherapy. The need for prostate biopsy is usually determined by PSA within 6 to 12 months after surgery. The literature reports a high rate of negative biopsies, 87-98%. Of course, a negative biopsy does not mean that the tumor is completely gone, as with radiation therapy for prostate cancer, and a negative biopsy simply indicates a decreased likelihood of treatment failure.
Short-term complications include scrotal penile edema, glandular edema, and penile numbness, which are mostly self-resolving. Long-term complications include urethral fistula, urinary incontinence, erectile dysfunction, and urethral carrion formation.
Salvage cryotherapy for prostate cancer has also been attempted [34-36], and the indications are PSA <4 ng/ml, long PSA doubling time, no seminal vesicle invasion, life expectancy of 10 years or more, and no distant metastases. There is a lack of reports that endocrine therapy before salvage cryotherapy can be beneficial, but endocrine therapy can reduce prostate volume. It is generally considered that a positive re-biopsy or a persistent rise in PSA greater than 0.5 ng/ml is generally considered a treatment failure. After applying two cycles of treatment, some scholars have reported a 93% negative re-biopsy rate and a 66% biochemical recurrence-free survival rate. A preoperative PSA >10 or Gleason score >=8 often predicts treatment failure. bahn reported a 7-year biochemical recurrence-free rate after salvage cryotherapy with a PSA <0.5 ng/ml in 59% and a PSA <1 ng/ml in 69%. ghafar et al. reported a PSA trough <0.1 ng/ml with a 1-year and 2-year quintuple biochemical recurrence rate of 86% and 74%. Of course the incidence of salvage therapy such as urethral fistula is significantly higher after surgery and these effects are accompanied by a significant risk of complications.
Conclusion
At present, the above mentioned techniques are still in their infancy in the treatment of tumors, and a series of preliminary clinical applications have been used in selective cases, with small sample sizes of studies and a limited number of reported literature, and the results of the studies are mostly based on imaging follow-up results, all with short follow-up periods, and the long-term cancer control rates are still undetermined. The specific treatment steps, technical success, complications and outcomes vary from study to study, and the relationship between tumor size and treatment time and treatment parameters is not reproducible, so further multicenter clinical trials are needed to observe the results of minimally invasive treatment techniques in treating kidney cancer patients with long-term survival rates beyond 5 years. The choice of minimally invasive treatment still needs to be made with great care, taking into full consideration the patient’s wishes, tumor-related factors, variability of techniques and diversity of follow-ups.
Minimally invasive treatment of solid tumors is a general trend in the development of modern medicine, and radiofrequency ablation technology, as one of the important ones, will certainly have a faster development in the coming years, and the safety and effectiveness of the treatment will be the focus of more scholars. For kidney and prostate, while referring to the experience of liver radiofrequency ablation, we should combine the organ’s own characteristics and conduct more in-depth basic and clinical research, so that the technology can better serve the clinical treatment.
Numerous studies have shown that with the continuous improvement of minimally invasive treatment equipment, the gradual improvement of intraoperative monitoring technology, and the increasing maturity of operational experience, minimally invasive treatment technology will play an increasing role in the field of kidney cancer prostate cancer treatment.