Precision oncology: The role of minimally-invasive ablation therapy in the management of solid organ tumors

Abstract

Solid organ tumors present a significant healthcare challenge, both economically and logistically, due to their high incidence and treatment complexity. In 2023, out of the 1.9 million new cancer cases in the United States, over 73% were solid organ tumors. Ablative therapies offer minimally invasive solutions for malignant tissue destruction in situ, often with reduced cost and morbidity compared to surgical resection. This review examines the current Food and Drug Administration-approved locoregional ablative therapies (radiofrequency, microwave, cryogenic, high-intensity focused ultrasound, histotripsy) and their evolving role in cancer care. Data were collected through a comprehensive survey of the PubMed-indexed literature on tumor ablation techniques, their clinical indications, and outcomes. Over time, emerging clinical data will help establish these therapies as the standard of care in solid organ tumor treatment, supported by improved long-term outcomes and progression-free survival.

Key Words: Minimally-invasive; Non-invasive; Solid organ tumor; Ablation; Locoregional

Core Tip: Minimally invasive tumor ablation techniques, including radiofrequency ablation, microwave ablation, cryoablation, high-intensity focused ultrasound, and histotripsy offer substantial benefits in treating solid organ tumors. These techniques provide effective localized treatment that minimizes damage to surrounding tissues, reduces recovery times, and enhances patient outcomes. Their evolving role in precision oncology demonstrates the potential to tailor interventions to individual patient needs, significantly improving therapeutic efficacy and patient care.

INTRODUCTION

Solid organ tumors present a profound health challenge globally, with specific cancers demonstrating the vast burden they place on healthcare systems. Hepatocellular carcinoma (HCC), primarily seen in East Asia and Africa, results in over 800000 deaths each year, largely attributable to high prevalence of hepatitis infections[1]. Lung cancer, especially non-small cell lung cancer (NSCLC), remains the deadliest cancer worldwide, driven largely by tobacco use and environmental factors[2]. Similarly, the incidence of renal cell carcinoma (RCC) is increasing globally, spurred by risk factors such as cigarette smoking, obesity, and hypertension, as well as better diagnostic techniques methods[3,4]. Even less common cancers like desmoid tumors, though not as prevalent, still contribute significantly to healthcare burdens due to their aggressive nature and the morbidity they cause[5]. This collective impact is reflected financially, with kidney and liver cancers alone accounting for an estimated $2.2 trillion in world economic burden in 2017, underscoring the economic strain these diseases place on health systems[6].

Minimally invasive locoregional therapies have dramatically altered the treatment landscape for solid organ tumor treatment[7]. Current examples of locoregional techniques include: Transcatheter directed arterial therapies like transarterial chemoembolization (TACE) and transarterial radioembolization; transcatheter chemical delivery for cytotoxic and therapeutic compounds; electrical current-mediated cell membrane perforation in irreversible electroporation, and minimally invasive ablative techniques for site-specific tumor destruction[8,9]. Historically, radiofrequency ablation (RFA) marked the beginning of a new era in the late 20^th century, proving effective for in situ destruction of tumors[10]. Techniques like microwave ablation (MWA) and cryoablation (CA) gained acceptance thereafter in the early 2000s, particularly for HCC, RCC, and NSCLC[11-13]. High-intensity focused ultrasound (HIFU), originally used in the operative treatment of Parkinson’s disease, has seen increasing use with prostate, liver, and breast cancers[14,15]. In addition, new technologies like histotripsy now offer alternatives for treating tumors near vital structures without risking thermal damage, and uniquely with respect to histotripsy, completely non-invasively[16,17].

Minimally invasive locoregional therapies offer both curative and temporal approaches for solid organ tumors. Curative approaches aim to eradicate early-stage tumors, while temporal approaches extend symptom-free survival by reducing tumor burden in advanced cases[18]. Both through our own experience with locoregional therapies at our institution and through the growing body of literature on this topic, we believe minimally invasive tumor ablation to be an increasingly powerful tool in oncology[19]. This review explores a spectrum of locoregional therapies and their application in HCC, RCC, NSCLC, and desmoid tumors. A nuanced understanding of the benefits and limitations of each modality is crucial for tailoring patient treatment strategies and integrating these therapies into comprehensive cancer care.

LOCOREGIONAL MINIMALLY-INVASIVE TUMOR ABLATION THERAPIES

Minimally invasive locoregional ablation therapies target tumors with remarkable precision while minimizing damage to surrounding tissues. Here, we describe each modality, detailing its mechanisms and specific applications. A summary of the techniques discussed is presented in Table 1.

Table 1 Overview of minimally invasive ablation techniques.

Technique	Mechanism	Frequency range	Max temperature	Tumor types treated	Strengths	Limitations	Common complications
Radiofrequency ablation	High-frequency currents to induce coagulative necrosis	460-500 KHz	100 °C	Adrenal gland, bone, breast, kidney, liver, lung, pancreas, thyroid	Oldest technique, low cost, minimal equipment	Requires conductivity, heat sink, less effective over time	Bleeding, pain, infection, tumor seeding, skin burns, post-RFA syndrome
Microwave ablation	Electromagnetic waves to induce coagulative necrosis	300 MHz-300 GHz	150 °C	Adrenal gland, bone, breast, kidney, liver, lung, prostate, spleen, uterus	Higher temps quickly, no conductivity needed, multiple probes for larger ablation	Cables can burn patient, requires cooling, less precise	Bleeding, pain, infection, tumor seeding, skin burns, post-ablation syndrome
Cryoablation	Extreme cold to induce cell death	N/A (cryogenic gases)	-196 °C	Bone, breast, kidney, liver, lung, prostate, skin	No heat, vessel occlusion, minimal damage to nearby tissues, multiple probes for larger ablation	Specialized gases needed, safety hazard with compressed gases	Infection, pain, bleeding, cryoshock, cryoreaction
High-intensity focused ultrasound	High-intensity ultrasound to generate localized heat and necrosis	0.8-3.5 MHz	Exceeds 60 °C rapidly	Bone, breast, desmoid, kidney, liver, pancreas, prostate, uterus	Non-invasive, high precision, lower risk of off-target damage	Requires anesthetics, affected by tissue echogenicity	Skin burn, pain, fistula, local edema, hyperpigmentation
Histotripsy	Cavitation bubbles to mechanically disintegrate tumors	250 KHz-6 MHz	N/A	Brain, breast, kidney, liver, muscle, pancreas, prostate, skin, thymus	Non-invasive, non-thermal, high precision, lowest risk of off-target damage	Requires anesthetics, affected by tissue echogenicity, experimental, low clinical data	Immune-mediated responses

N/A: Not applicable; RFA: Radiofrequency ablation.

RFA

RFA uses high-frequency alternating currents (460-500 KHz) delivered through an electrode probe to heat tissue and induce coagulative necrosis[20,21]. The radiofrequency range in the electromagnetic spectrum lies between 3 Hz to 300 GHz. The RF probe, inserted percutaneously using image guidance into or near the tumor, creates a circuit with the generator, the probe (cathode), the patient, and the grounding pad (anode) placed on the patient’s body. Dipole molecules (mostly H₂O) align and vibrate with the alternating current, generating heat through molecular friction (Joule effect)[21,22]. This energy is proportional to the current and tissue impedance and diminishes exponentially with distance from the probe. Time to cell death is inversely proportional to the local temperature achieved: 15 minutes at 45 °C, 2 seconds at 55 °C, and < 1 second at 100 °C[20,21]. The goal of RFA is to heat the area around the probe to 50-100 °C for 4-6 minutes to ensure local cell death while also creating a “surgical margin” of healthy tissue without damaging nearby structures. Care must be taken to avoid rapid heating to temperatures > 100 °C to avoid carbonization/burning of tissue - the carbonized tissue is non-conductive and thus would behave as an insulator and greatly reduce further tumor destruction.

Excellent results have been seen with RFA in the treatment of small solid tumors (< 3 cm in diameter) in lung, liver, and kidney[23-25]. Progression-free survival (PFS) has been shown to be sufficiently high with RFA to recommend in lieu of surgery in tumors that are: < 2 cm in diameter, not located near major vasculature, and able to be clearly visualized with imaging techniques. Tumors that do not meet these criteria pose too high of a risk of incomplete necrosis and therefore high risk of tumor recurrence. The introduction of advanced imaging techniques, such as fusion imaging, to guide therapy has improved the technical success and local tumor progression statistics of RFA by enhancing tumor visibility and therefore tumor targeting, safety margin evaluation, and importantly, the detection of incomplete ablation allowing for immediate retreatment of residual tumor. A recent single-center study investigating advanced imaging-guided RFA in liver malignancies (primary and metastatic) that were poorly visible on B-mode ultrasound (US) (n = 248 patients) found contrast-enhanced US-computed tomography (CT)/magnetic resonance imaging (MRI) fusion imaging increased tumor identification by 87.7% compared to B-mode US alone[26].

RFA has a mortality of 0.3%-0.8% and a morbidity of 2%-10%[27]. Complications include those common to all surgical procedures for tumors: Bleeding, post-procedure procedure pain, infection, damage to nearby structures, and tumor seeding. Unique to RFA, potential complications include: Skin burns (improper placement of grounding pad) and post-RFA syndrome, characterized by fever and flu-like symptoms within the first 24 hours following the procedure and occurs in roughly one-third of patients[10,28]. Post-RFA syndrome is usually self-limited and resolves in 7-10 days.

MWA

MWA utilizes electromagnetic waves in the microwave range (300 MHz to 300 GHz, typically either 915 MHz or 2.45 GHz is chosen) to generate heat and induce coagulative necrosis in tumor tissue[29,30]. A magnetron or solid-state microwave source creates the microwave energy, which is passed percutaneously into the tumor via coaxial cables to microwave antennae. The oscillating waves of magnetic radiation force polar molecules (mostly H₂O) to oscillate with the electric field to increase molecular kinetic energy and thus raise local temperature (dielectric heating).

Compared to RFA, MWA achieves lethal temperatures faster in larger volumes and does not require electrical conductivity[29,30]. Without that limitation, MWA does not require electrical grounding is thus used for larger tumors in liver, lung, kidney, prostate, and bone most commonly[31]. MWA offers another advantage in being able to use multiple probes/antennae within the same tissue to create focused hot-spots of differing geometry. The electric fields radiating from each antenna can be aligned with each other to overlap in phase in specific regions of the tumor and increase the intensity of the radiation by a factor of N², where N is the number of antennae used[29]. Currently, state of the art devices can achieve single-antenna ablation sizes up to 5 cm, and possibly larger, in liver tissue[32-35]. Multi-antenna arrangements, on the other hand, can achieve ablation volumes as high as 263.9 cm³[36]. As MWA can higher temperatures faster, it leads to tissue necrosis faster, but consequently produces a larger minimum ablation volume compared to RF, which only efficiently heats the tissue immediately surrounding the probe[37]. Similar to RFA, advanced imaging guidance improves the accuracy of MWA. In a single-center study, patients with metastatic liver lesions poorly conspicuous on US (n = 35 patients) experienced an 83% improvement in lesion conspicuity with CT/US-fusion imaging[38].

MWA also has a limitation in that the coaxial cable that carries the microwave energy to the antennae and passes through the patient percutaneously also gets hot and needs to be cooled by various means (cooling jackets, insulation, or running water), but can damage the entire tract leading up to the antennae. This shortcoming has been mitigated nearly completely by introduction of advanced cooling systems, including pulsed radiation, cable shielding (tri-axial cable structure), the use of compressed carbon dioxide gas and a quarter-wave impedance transformer (choke), which electrically mitigates return currents on the outer conductor and retains more radiated energy within the desired region[39-43]. Other complications associated with MWA are similar to those associated with RFA, as both are thermal ablation techniques: Bleeding, post-procedure procedure pain, infection, damage to nearby structures, tumor seeding and a “post-ablation syndrome” that is analogous to post-RFA syndrome[31].

CA

CA is a technique that uses extreme cold to induce cell death in tumor tissue via percutaneously or laparoscopically inserted cryoprobes into or near a tumor under imaging guidance. This technique leverages the physical properties of gases like argon and nitrogen to achieve temperatures as low as -196 °C[44]. An example cryoprobe functions by high pressure argon flowing through a small channel in the core of the probe into a larger low-pressure space within the probe, expanding rapidly and absorbing ambient heat thereby rapidly lowering the temperature of the metal probe tip and freezing the surround tissue. During the freezing process, intracellular and extracellular ice crystals form which then disrupt cellular structures and organelles, rupture cell membranes, and occlude microvessels leading to tissue ischemia and cell death[45]. The ice ball generated at the probe tip typically extends several millimeters beyond the cryoprobe - best results are achieved when the tumor is smaller than the diameter of the ice-ball created so the entire tumor and a surrounding margin of healthy tissue (at least 5 mm) can be frozen to help ensure complete tumor ablation. Like MWA, multiple probes can be employed simultaneously to achieve a larger area of effect[46]. Following the freezing phase, a rapid thawing phase is initiated either naturally or by using helium gas, which leads to further cellular injury through osmotic shock and vascular stasis. Typically, two or more freeze-thaw cycles are performed in one session to maximize tumor destruction.

CA is particularly effective for treating small to moderately sized tumors (usually < 3 cm) in various organs, including the kidney, liver, lung, breast, prostate, skin, and bone[47-49]. It is especially beneficial for patients who are poor candidates for surgery due to comorbidities or tumor location and some centers have shown success with tumors larger than 4 cm when multiple probes are used[46]. Studies have shown that CA provides excellent local control with minimal damage to surrounding tissues, making it an attractive option for tumors near critical structures. However, a rare risk with CA is post-procedure “cryoshock” - a syndrome presenting with multi-organ failure, coagulopathy, and disseminated intravascular coagulation. A milder complication of “cryoreaction” can also occur, which is characterized by fever, chills, tachycardia, tachypnea, and elevated creatinine and has been noted to have an incidence of 0.8% in HCC CA[50]. CA has a low mortality rate (approximately 0.1%-0.5%) and a morbidity rate of 5%-15%, which includes risks common to other percutaneous procedures such as infection, bleeding, and organ-specific complications.

HIFU ablation

HIFU is a non-invasive therapeutic technique that employs high-intensity US waves transcutaneously focused onto a single point (target tumor) to generate localized heat and lead to coagulative necrosis of the targeted tissue while sparing the surrounding healthy structures[51]. Typically, energy is delivered in the range of 0.8-3.5 MHz in 4-8 second pulses, with 20-40 second inter-pulse intervals for the treatment zone to cool[52]. The intensity is sufficient at this focal point to raise the temperature of the tissue precisely and rapidly, often exceeding 60 °C within seconds while minimizing the thermal spread to adjacent areas. The treatment is usually performed under real-time imaging guidance, such as US or MRI with thermometry, to ensure accurate targeting and monitoring of the ablation process. Minimizing patient motion is critical so anxiolytic, analgesic, and anti-spasmodic agents are delivered peri-procedure to reduce movement and gastrointestinal peristalsis[53].

This ability to precisely and selectively generate heat is leveraged in two other ways: Localized drug delivery and tumor cell permeabilization[53]. US waves can also be focused at a higher frequency (usually 20 KHz to 5 MHz) in short 4-16 microsecond pulses to create transient holes in the plasma membrane of target tissue by acoustic cavitation[54,55]. A review of the mechanical details of fluid cavitation is beyond the scope of this review. Briefly, as an electric current is applied to the piezoelectric crystal within the US transducer, the crystal expands and contracts synchronously. In these ablation technologies, the current frequency is raised to ultrasonic levels (over 20 KHz), causing the piezoelectric crystal to expand and contract at the same frequency. With each expansion, the transducer compresses water in front of it (contraction wave), and with each contraction, contracts the water ahead of it (rarefaction wave). The compression waves create acoustic pressure and rarefaction waves create low-pressure waves that are below the vapor pressure of water, instantly turning it to vapor, which forcefully implodes when another high pressure hits it. This implosion results in immense release of energy that causes the pores to form in the cell membrane in a process called “sonoporation”.

In application of sonoporation, one study observed the formation and function of these cavitation bubbles and found that a single 8 microsecond pulse could create a 0.17 MPa microenvironment (air pressure at sea level = 0.1 MPa = 1 atm) resulting in a single hole in the plasma membrane that lasted for 1 minute[56]. In this way, HIFU can transiently increase permeability and/or the activity of locally delivered chemotherapeutics, while simultaneously reducing systemic off-target exposure and toxicity.

HIFU is used to treat a variety of solid tumors, including those in the liver, prostate, pancreas, breast, bone, kidney, desmoid, and uterine leiomyomata[53,57]. Its non-invasive nature makes it an attractive alternative to surgery, especially for patients who are not suitable candidates for invasive procedures. HIFU can often be performed on an outpatient basis, which reduces hospital stay, recovery times, and overall utilization of healthcare resources compared to surgical intervention[57]. The efficacy of HIFU in tumor ablation has been demonstrated in multiple studies showing promising results in terms of local control and patient outcomes. For instance, in prostate cancer treatment, HIFU has been shown to achieve high rates of biochemical recurrence-free survival comparable to other standard therapies. Similarly, in uterine leiomyomata, HIFU has been effective in reducing symptoms and improving patient quality of life. This procedure has a low mortality rate (near 0%) and low morbidity rate. The limitations are similar to those of diagnostic US in that deep structures (> 10 cm below the skin surface) and structures near or shielded by anechoic gas filled structures or hyperechoic reflective structures (e.g., bone) will greatly reduce HIFU effectiveness[58]. While damage to local structures is less than other modalities and surgery, local recurrence is as high as 23% for prostate cancer[59]. Even with that, the non-invasive outpatient nature of the procedure lends itself well to salvage therapy for late-stage cancers, tumor debulking, and improvement of quality of life.

Histotripsy

Histotripsy is an innovative evolution of HIFU sonoporation. Whereas HIFU ablation uses US waves to non-invasively induce coagulative necrosis in tumor tissue and sonoporation uses the same kind of energy to create short-lived holes in tumor cell plasma membranes, histotripsy is non-thermal ablation of tumor tissue using microscopic cavitation bubbles. Image guidance is used to focus US waves (typically at 250 KHz to 6 MHz) in short 0.5 to 5 microsecond pulses to create waves of high acoustic pressure exceeding 26 MPa, or 256.6 times the air pressure at sea level. Short bursts of energy are used in this technique to maximize the number and distribution of microbubbles to disintegrate tumors mechanically without heating the tissue and while avoiding thermal damage to local structures[17]. Histotripsy uses two approaches to create targeted destructive clouds of cavitation bubbles: Intrinsic threshold and shock-scattering. The intrinsic threshold, or “microtripsy”, approach uses one to two-cycle pulses to create sub-millimeter clouds of cavitation bubbles for small-volume high-precision ablation. Shock-scattering, on the other hand, uses a multi-pulse (typically 3-20 pulses) approach to create larger dense clouds of cavitation bubbles for large-volume ablation that is less precise, but more efficient than the intrinsic threshold approach. The resulting breakdown of tumor tissue at a microscopic level leaves behind a liquefied region of necrotic tissue that the body can then reabsorb over time[60]. Interestingly, some studies have noted activation of T-lymphocytes after histotripsy leading to immune-mediated destruction of both the target tissue and non-treated tumors (the abscopal effect) in murine models[61,62], presenting more potentially translational approaches.

Histotripsy is currently under investigation for treatment of a variety of cancers, including tumors in the liver, skin, kidney, prostate, breast, pancreas, thymus, muscle, and brain[16,63]. Its non-thermal and non-invasive nature makes it particularly attractive for tumors adjacent to critical structures where thermal ablation risks collateral damage or energy loss via heatsink. With successful completion of clinical trials, histotripsy is currently Food and Drug Administration approved for use in both primary liver tumors (HCC and neuroendocrine tumors) and liver metastases of primary colon, rectum, and breast cancers. A phase I clinical trial in 2019 (clinicaltrials.gov identifier: NCT03741088) studied histotripsy therapy in 11 malignant liver tumors in 8 patients and found all targeted tumors had locally regressed 2 months post-treatment with no adverse effects noted during the study[64].

POST-THERAPY OUTCOMES BY REGION AND TECHNIQUE

Understanding the post-therapy outcomes of minimally invasive tumor ablation techniques is crucial for optimizing patient care and improving long-term prognoses. This section provides an overview of post-therapy outcomes, systematically categorized by tumor types and specific ablation methods. We will examine outcomes in liver, kidney, lung, and desmoid tumors; we will then identify treatment success/response rates, overall survival (OS), PFS, and potential complications associated with different minimally invasive techniques. Techniques under review include RFA, MWA, CA, HIFU, and histotripsy. A summary of the malignancies discussed is presented in Table 2.

Table 2 Clinical indications and outcomes for ablation techniques.

Tumor type	Ablation technique	Indications	Response rate	1-year PFS	1-year OS
Hepatocellular carcinoma	RFA, MWA, CA, HIFU, histotripsy	Solitary tumors < 3 cm (RFA), recurrent or aggressive disease, association with vasculature/biliary system	91.8% (RFA), 98.8% (MWA), 94% (CA), 90% (HIFU), 100% (histotripsy, preliminary)	75% (RFA), 87.6% (MWA), 84.4% (CA), 63.6% (HIFU), limited data (histotripsy)	93.3% (RFA), 95.9% (MWA), 100% (CA), 59.48% (HIFU), limited data (histotripsy)
Non-small cell lung cancer	RFA, MWA, CA	Early-stage non-surgical candidates, medically inoperable elderly patients, metastatic	79.5% (RFA), 100% technical success (MWA), 100% (CA), limited data (HIFU, histotripsy)	54% (RFA), 93.7% (MWA), 100% (CA), limited data (HIFU, histotripsy)	100% (RFA), 99% (MWA), 97.5% (CA), limited data (HIFU, histotripsy)
Renal cell carcinoma	RFA, MWA, CA, HIFU, histotripsy	Stage T1a and T1b, high-risk patients, oligometastatic	95.5% technical success (RFA), high (MWA), 92.6% technical success (CA), limited data (HIFU, histotripsy)	> 97% (RFA), 100% (MWA), 95.6% (CA), limited data (HIFU, histotripsy)	> 97% (RFA), 99% (MWA), 98% (CA), limited data (HIFU, histotripsy)
Desmoid tumors	RFA, MWA, CA, HIFU, histotripsy	Combination with chemotherapy, difficult anatomical locations, recurrence management	88.9% (MWA), 80% (CA), 47.3% (HIFU), limited data (RFA, histotripsy)	85.1% (CA), limited data (RFA, MWA, HIFU, histotripsy)	69.3% (HIFU, 5-year), limited data (RFA, MWA, CA, histotripsy)

PFS: Progression-free survival; OS: Overall survival; RFA: Radiofrequency ablation; MWA: Microwave ablation; CA: Cryoablation; HIFU: High-intensity focused ultrasound.

HCC

HCC is the sixth most common cancer and the third leading cause of cancer death in the world[1]. With an estimated 725000 new cases globally in 2020, HCC is responsible for a significant healthcare burden necessitating innovative treatment strategies[1,65]. Specific etiologies vary and include chronic infection with hepatitis B or C virus, non-alcoholic and alcoholic fatty liver disease, tobacco smoke, chronic alcohol abuse, hemochromatosis, and α1-antitrypsin deficiency and 85%-90% of cases are comorbid with cirrhosis[66,67]. Current treatment guidelines from the American Association for the Study of Liver Diseases recommend solitary tumors ≤ 5 cm (if ineligible for surgery) should be treated with local ablative therapies with curative intent (level 1, strong recommendation), and thermal ablation should be considered for small tumors (≤ 3 cm) (level 1, strong recommendation)[68]; however, treatment paradigms are also in place for recurrent or highly aggressive disease requiring a multimodal approach[69]. Strategies are also dependent on stage, which is classified by the Barcelona Clinic Liver Cancer (BCLC) classification system. Curative strategies are available for early stages (BCLC stage 0 to stage A) and typically include surgical resection, tumor ablation, or liver transplantation[70,71]. Most patients, however, become symptomatic late in the disease course and present with advanced-stage malignancy (BCLC stage B or C), limiting viable treatment options.

There is a growing interest in locoregional ablative techniques in both primary cancers of the liver and tumors for which the primary malignancy is extrahepatic[72]. Secondary hepatic cancers occur more than 20-fold more frequently than primary hepatic cancer[73]. Colorectal adenocarcinomas account for the majority of cases, followed by pancreatic and breast primary cancers, and more rarely yet lymphoma, sarcoma, and melanoma[74]. The liver’s penchant for metastatic disease is owed in large part to its dual blood supply, which also makes the liver uniquely accessible to minimally invasive therapies. This relationship has been demonstrated in the results of the CLOCC trial (Chemotherapy Plus Local Ablation Versus Chemotherapy) (clinicaltrials.gov identifier: NCT00043004, eortc.org identifier: EORTC-40004), a randomized phase II trial, which showed significantly improved OS over 9.7 years in patients with unresectable colorectal liver metastases (CRLM) who received combined RFA and chemotherapy (median OS: 45.6 months) vs chemotherapy alone (median OS: 40.5 months)[75]. Most recently and most strikingly, results from the COLLISION trial (CRLM: Surgery vs thermal ablation), a phase III single-blind prospective randomized controlled trial (RCT), show that after 28.8 months there is an insignificant difference in OS between patients with small resectable CRLM (≤ 3 cm) who received surgical resection or minimally invasive thermal ablation[76]. This similarity in outcomes between surgical resection and locoregional intervention, and the lower morbidity and mortality profile inherent to minimally invasive techniques, could potentially lead to locoregional ablation becoming the standard of care in small resectable CRLM in lieu of surgery. Extensions of the COLLISION trial, the COLLISION RELAPSE (chemotherapy + repeat locoregional treatment vs repeat locoregional treatment alone for recurrent CRLM, clinicaltrials.gov identifier: NCT05861505) and COLLISION-XL (stereotactic body radiotherapy vs MWA for 3-5 cm CRLM, clinicaltrials.gov identifier: NCT04081168) trials are currently ongoing.

Tumors that are aggressive, intimately associated with vasculature and the biliary system, or are multifocal within the liver are amenable to locoregional therapies[77,78]. Further, the incorporation of advanced imaging guidance modalities improves targeting precision to improve procedure safety, particularly lesions proximal to other structures[79]. Advanced imaging also aids in the identification of more lesions, more accurate ablation margins, and consequently improved PFS[26,80]. Minimally invasive ablation techniques create an opportunity to provide therapy for these patients, who may not be eligible for surgery.

RFA: As one of the oldest ablation techniques currently in use, multiple outcome studies and RCTs have been conducted for RFA in HCC[19,81-83]. A 2022 single-center RCT comparing outcomes of laparoscopic liver resection to those of RFA for small (< 3 cm) HCC tumors (n = 75 per group) found 91.8% of patients who underwent one session of RFA had complete ablation and no tumor on post-op day 3 (clinicaltrials.gov identifier: NCT02243384)[84]. The remaining patients received a second RFA treatment, which resulted in complete tumor ablation. OS at 1, 3, and 5 years for RFA was lower than those of surgical resection by 1.47%, 1.63%, and 9.1%, respectively (RFA OS: 1-year: 93.3%, 3-year: 78.7%, and 5-year: 67.9%). While recurrence rate was higher overall in the RFA group, PFS rates were not significantly different between groups. Procedure-related complications were less frequent in the RFA group compared to surgical resection at 10.7% vs 29.3%, respectively.

A multi-center retrospective analysis of data from 2008 to 2010 of patients who underwent RFA for HCC (n = 36 patients) showed similar results with OS at 1, 3, and 5 years as 91.7%, 72.2%, and 53.3%, respectively. This study found PFS at 1, 3, and 5 years to be 75%, 72.2%, and 53.3%, respectively[85]. This can be attributed to the significantly shorter procedure time for RFA (94.3% shorter) and intrinsically less invasive nature of RFA. Additionally, a single-center study of 3 dimensional contrast-enhanced US-guided RFA of HCC lesions (n = 84 patients) led to complete ablation in 100% of patients enrolled and local tumor progression in only 8 of the enrolled patients, all of whom had an ablation margin of less than 5 mm[86].

MWA: Advances in imaging-guidance and the accumulation of increasing clinical successes with locoregional therapy have led to the American Association for the Study of Liver Diseases to consider thermal ablative treatment, such as MWA, first-line in early-stage HCC[68,87]. When compared to surgical resection, and matching analysis of propensity score for HCC ≤ 5 cm showed MWA to be comparable, if not superior to resection in terms of OS, disease free survival, tumor recurrence and complications[88,89].

Demonstrating the merit of minimally invasive locoregional therapy, a retrospective analysis of MWA for HCC over 13 years at a single center (n = 425 patients) showed a high response rate at 98.8%[90]. OS was reported as 95.9%, 78.5%, 60.2%, and 42.5% at 1, 3, 5, and 10 years, respectively. Of the group overall, 131 patients (30.8%) experienced disease recurrence and thus poorer results due to more aggressive disease. Consequently, PFS (n = 294/425 patients, 69.18%) at 1, 3, and 5 years was 88.9%, 63.4%, and 47.9%, respectively. Complication rates were also consistently lower for the less invasive MWA when compared to surgical resection. Comparing the effectiveness of CT- (n = 47 patients) vs MR- (n = 54 patients) guided MWA of HCC lesions ≤ 5 cm, a single center study showed similar OS and local tumor progression, though MR-guidance was associated with shorter procedure time and significantly fewer complications[87].

CA: A retrospective analysis with propensity score matching of patients who underwent CT-guided CA for HCC proximal to the portal vein (n = 32 patients), termed perivascular HCC, compared to those who underwent CT-guided MWA (n = 32 patients) showed a response rate of 94% in CA vs 91% in MWA[91]. Over a 36-month follow-up period the MWA group experienced a recurrence rate of 25% vs 16% in CA. OS at 36 months was higher in the CA group at 53.1% vs 40.6% in the MWA group. Recurrence rate was also lower in the CA group at 16% vs 25% in the MWA group. Complications were fewer in CA and noted in 25% of CA patients (peritoneal effusion) vs 34% of MWA patients (pleural effusion, peritoneal effusion, and bile leakage). A single-center study of CA therapy in 45 treatment-naïve HCC patients found PFS at 1 and 2 years to be 84.4% and 62.2%, respectively[92].

HIFU ablation: A retrospective analysis of data from 2007 to 2010 (n = 49 patients) found a 90% response rate for HIFU treatment of HCC as a bridge to transplant[93]. A meta-analysis of 6 cohort studies comparing outcomes in HCC therapy after HIFU vs TACE showed partial and complete tumor response rates were higher, though not statistically significantly, in the HIFU group (44.57% HIFU vs 34.55% TACE)[94]. OS at 6, 12, and 24 months post-treatment were found to be 92.96%, 59.48%, and 54.93%, respectively for the HIFU group vs 79.76%, 55.15%, and 39.29%, respectively for the TACE group. This difference was significantly higher in the HIFU group at 6 and 24 months (6-month, P = 0.01, 12-month P = 0.03), but insignificantly different at 12 months (12-month, P = 0.27). There was no significant difference in disease recurrence between the two groups. There was also no significant difference in complication rates (postoperative bleeding, skin burn, and transaminitis) for both groups. Another single-center study of HIFU in HCC from 2006 to 2010 (n = 47 patients) found 1- and 3-year OS to be 97.4% and 81.2%, respectively and corresponding PFS to be 63.6% and 25.9%, respectively[95]. These results demonstrate viability for the non-invasive HIFU approach to achieve the same level of effectiveness as invasive TACE in HCC therapy.

Histotripsy: Histotripsy is still in its early stages of clinical use having only recently received Food and Drug Administration approval for use in the treatment of liver tumors in 2023, thus long-term outcome data is limited. A first in-human, non-randomized, multi-center clinical trial in Barcelona investigated the use of histotripsy in primary and metastatic liver tumors from 2018 to 2019 (clinicaltrials.gov identifier: NCT03741088) and showed a 100% technical success rate (n = 11 tumors in 8 patients)[96]. A follow-up multi-center clinical trial in Europe (Germany, Italy, Spain, United Kingdom) (clinicaltrials.gov identifier: NCT04573881) is currently ongoing (began 2021)[97]. In the laboratory setting, histotripsy treatment of orthotopic liver tumor in a Sprague-Dawley rat model (histotripsy vs untreated control, n = 11 rats per group) showed an 81.8% response rate with tumor burden reduction and a statistically significant increase in survival time of 10 weeks in the treatment group vs 1.45 weeks in the untreated controls (P < 0.0001)[98].

Lung tumors

Lung cancer remains a leading cause of cancer-related mortality worldwide, accounting for nearly 1.8 million deaths annually[2,99]. The primary etiologies include tobacco smoking, responsible for over 80% of cases, chronic obstructive pulmonary disease, and exposure to environmental pollutants, arsenic, asbestos, and radon. Despite advances in early detection and targeted therapies, lung cancer prognosis remains poor, with a 5-year survival rate in the United States of 20.5%. By disease stage, the 5-year survival rate is 59.0% for early stage I to II, 31.7% for stage III, and 5.8% for late and advanced stage IV malignancy. Often asymptomatic in early stages, more than half of lung cancer cases in the United States are diagnosed at stage IV[2].

Lung cancer is broadly categorized into small-cell lung cancer (SCLC) and NSCLC, with SCLC typically presenting as a disseminated and more aggressive disease. Treatment strategies depend on histological type, tumor size and location, pleural involvement, surgical margins, lymphatic involvement, and tumor grade. For stage I SCLC without nodal involvement, surgical lobectomy (curative intent) is recommended, with chemotherapy for more advanced disease (grade 4A recommendation)[100]. For NSCLC at stage I to II, surgical lobectomy (curative intent) is appropriate, while nonsurgical candidates should be considered for percutaneous ablation or stereotactic body radiation therapy (grade 2C recommendation)[101].

Recent updates from professional societies such as the Society of Interventional Radiology, National Comprehensive Cancer Network, and the American College of Chest Physicians highlight the general concordance that thermal lung ablation is a safe and effective option for early-stage nonsurgical candidates[102]. Given that most SCLC and advanced NSCLC cases are not surgical candidates due to high comorbidity and advanced disease with metastases (commonly to liver, adrenal glands, bone, and brain), minimally invasive therapeutic techniques address a critical need for a large patient population[103,104].

RFA: A single-center retrospective analysis of patients with primary and metastatic lung malignancy from 2005 to 2013 (n = 49 patients) showed a response rate of 79.5%[105]. OS at 1, 2, and 3 years for primary lung cancer was 100%, 86%, and 43%, respectively. PFS at 1, 2, and 3 years was 54%, 43%, and 36%, respectively. Common complications included chest pain in more than half of the patients treated and was suggested to be secondary to possible burn injury. Other less common complications included pneumothorax, hemoptysis, pneumonia, and pleural effusion.

A meta-analysis of data from 14 RCTs, cohort studies, and case-control studies (n = 1387 participants) investigated the change in outcomes for patients undergoing chemotherapy vs chemotherapy supplemented with RFA for malignant pulmonary tumors[106]. An overall 50% reduction in risk of death was calculated for combination therapy of chemotherapy and RFA compared to chemotherapy alone. Interestingly, a significant benefit was observed with combination therapy, but not with either therapy alone, implying a possibly synergistic relationship between the therapies. As such, RFA could not only be a good option for non-surgical candidates, but also a potential alternative for those who would not tolerate chemotherapy.

MWA: A single-center analysis investigated outcomes for MWA of medically inoperable early-stage NSCLC in elderly patients (age ≥ 70 years) from January 2021 to October 2021 (n = 97 patients)[107]. With a technical success rate of 100%, OS at 1-year follow-up was found to be 99.0% and PFS at 1 year was 93.7%. Complications in this cohort included minor pulmonary hemorrhage (incidence = 9.3%), pneumothorax (incidence = 16.5%), and pleural effusion (incidence = 10.3%).

CA: A multicenter prospective study evaluated the efficacy of CA in metastatic lung cancer from 2012 to 2017 (n = 40 patients across 4 sites)[108]. Primary cancer diagnosis in these patients included colorectal cancer (42.5% of cases), RCC (17.5% of cases), and sarcoma (10% of cases), among others. OS at 1, 2, 3, and 5 years was 97.5%, 84.3%, 63.2%, and 46.7%, respectively. Another interesting measure from this study was chemotherapy-free survival, calculated at 1, 3, and 5 years as 79.9%, 51.6%, and 35.3%, respectively. A single-center study by a different group from 2017 to 2020 (n = 19 patients) reviewed outcomes in CA for primary lung cancer in patients age ≥ 80 years found OS at 1, 2, and 3 years to be 100%, 94%, and 94%, respectively, and PFS was 100% throughout the study period[109]. This study had an adverse event incidence of 37%, all of which were pneumothoraces.

HIFU ablation: There is as yet little clinical data in the use of HIFU in lung tissue. The use of US requires a medium through which the US waves can travel, thus solid tissue and liquid are the typical media used. US waves are attenuated significantly when traveling through air in lung tissue and this presents a technical challenge to the use of HIFU in lung malignancies. Some studies introduced, in ex-vivo human lung tissue and in-vivo animal models, a novel technique of flooding lung tissue with saline to aid in HIFU conduction and tumor targeting[110-112]. Another group is applying magnetic resonance guidance to aid accurate target ablation with focused US waves[113,114]. With the continued development of innovative approaches to overcoming its limitations, HIFU is poised to become a powerful tool in the future of lung cancer therapy.

Histotripsy: Similar to the technical challenges seen in HIFU, air-filled lung tissue provides poor acoustic access to sound waves used in histotripsy. Further work is needed in this area to develop a reproducible and safe methodology for the use of focused US waves in lung malignancy ablation.

Kidney tumors

RCC is the most common solid renal tumor with an annual incidence in the United States of 82000 and mortality of 15000 people each year[115-117]. Worldwide these numbers grow to 400000 new cases and 170000 deaths each year[115]. With improvements in accuracy and affordability of imaging technology, 67% of RCC cases are diagnosed incidentally - particularly striking as RCC commonly develops asymptomatically so patients often present for diagnosis with advance or metastatic disease[115,118]. Primary RCC tumors originate most often from the renal cortex, followed by transitional cell carcinoma of the renal pelvis, and rare others such as oncocytomas, collecting duct tumors, embryonal tumors (nephroblastoma), and renal sarcoma. The etiology is diverse and includes tobacco smoke, hypertension, obesity, chronic kidney disease, genetic factors (such as autosomal dominant polycystic kidney disease), chemical exposure, chronic hepatitis C virus infection, and sickle cell disease[119-121].

The Society of Interventional Radiology published a “Position Statement on the Role of Percutaneous Ablation in Renal Cell Carcinoma” in 2019, providing level C guidance (strength of recommendation: Moderate) on percutaneous thermal ablation (vs nephrectomy) in stage T1a RCC and level D guidance (strength of recommendation: Weak) on percutaneous thermal ablation for: (1) High-risk patients who are not surgical candidates for stage T1b RCC; and (2) Patients with oligometastatic disease who are not candidates for metastasectomy[122]. All percutaneous thermal techniques (RFA, MWA, or CA) were appropriate (level D guidance, strength of recommendation: Weak) and up to the discretion of the provider.

RFA: Multiple systematic reviews and meta-analyses have investigated the outcomes for RFA for patients with RCC, including a technical success rate of 95.5%, risk of recurrence between 4.1%-6.4%, and risk for major complications at 3.1%-3.7%[23,123-125]. When RFA is performed with advanced imaging-guidance, such as US-CT fusion imaging, a single-center retrospective analysis found no significant difference in 5-year disease free survival when compared to laparoscopic partial nephrectomy, but significantly less frequent and less severe postprocedural kidney injury and shorter hospital stay in the image-guided RFA group[126].

More recently, single centers have published safety and efficacy analyses for RFA for small renal masses. Over a study period of 12 years, the cumulative 5-year and 10-year radiologic recurrence was 6.6% and 16%, respectively at a single center (n = 90 patients)[127]. Cumulative incidence of cancer death was 4.5% at 10 years. A separate center showed a 15-year recurrence-free rate of 96.5% and a 15-year disease-free rate of 88.6%, with a 15-year metastasis-free and cancer-specific survival rate of 100%[128]. Indeed, data from these single centers with longer-term follow-up (15 and 20 years) will be invaluable in evaluating the long-term oncologic outcomes of patients treated using a minimally invasive technique vs those treated through partial nephrectomies.

MWA: A systematic review and meta-analysis investigated the outcomes for MWA for patients with RCC utilizing 27 retrospective studies (n = 1584 patients, 1683 tumors)[129]. Data were pooled from these studies from which outcomes measures were calculated revealing a 1-, 3-, and 5-year OS of 99%, 96%, and 88.1%, respectively. When compared to a prior meta-analysis published in 2018[130], both analyses supported similar technical outcomes, improved overall and cancer-specific survival at 3 and 5 years, and lower rates of both minor and major complications. However, the more recent study found higher rates of local regional recurrence (3.2% vs 2.1%). The authors further analyzed outcomes for patients with T1b RCC (n = 204 patients, 208 tumors), finding a recurrence rate of 4.2%, 3-year cancer-specific survival rate of 97.2%, and major complications incidence rate of 2.6%. A smaller single-center study reviewing survival outcomes for MWA treatment of RCC found PFS of 100.0%, 92.8%, and 90.6% at 1, 2, and 3 years[131].

CA: A single-center retrospective analysis of oncologic outcomes for patients who underwent CA for treatment of T1a RCC from 2005 to 2015 (n = 308 patients) determined OS at 1, 2, and 3 years post-treatment was 98%, 94.1%, and 87.6%, respectively[132]. PFS was found to be 95.6%, 93.3%, and 90.3% at 1, 2, and 3 years post-treatment, respectively.

Previously, different groups conducted systematic reviews and published the outcomes for CA: Technical success rate of 92.6%, local recurrence rate of 3.0%-8.0%, and a major complications rate of 1.8%[133-135]. More recently, a systematic review evaluated the outcomes of percutaneous CA vs partial nephrectomy in 14 retrospective studies for n = 6487 patients with stage T1a tumors[136]. Compared to patients undergoing partial nephrectomy, those who underwent percutaneous CA had lower overall complication rates and similar rates for metastasis-free survival and cancer-specific survival. Notably, while the rates for local recurrence were similar for cT1a tumors, percutaneous CA was associated with more local recurrences for cT1b tumors.

HIFU ablation: HIFU ablation is not a common ablative method for RCC. However, 1 single-center case series of 2 patients with RCC arising from kidney transplants utilized HIFU[137]. In both cases, post-procedural US did not reveal any complications and neither patient had recurrent tumors at 81-month follow-up.

Histotripsy: Histotripsy has been shown to be effective in animal models (rodent and porcine) of renal tumors by inducing direct apoptosis of tumor cells, indirect apoptosis through activation of intracellular pro-apoptotic pathways (e.g., cleaved-caspase-3), and though activation of the immune system through the abscopal effect[138-140]. Current human studies on efficacy and safety for patients with solid renal tumors are underway (clinicaltrials.gov identifier: NCT05820087).

Desmoid tumors

Desmoid tumors are rare tumors of clonal fibroblasts, related to the sarcoma family of malignancies, and account for 0.03% of all neoplasms and 3% of soft tissue tumors[5]. Also called desmoid fibromatosis or aggressive fibromatosis, these tumors are typically benign and do not cause metastatic disease, but are locally aggressive and cause great morbidity with proximal tissue invasion[141,142]. While an exact etiology is unknown and occurrence is generally sporadic, some cases are associated with familial adenomatous polyposis and are also seen in 10% of Gardner syndrome cases[143]. It is also hypothesized that mutations in the Wnt signaling pathway may play a causative role in the development of desmoid tumors[144,145]. Risks associated with development of these tumors include genetic predispositions, hormone exposure, and a history of trauma, pregnancy, or surgery[146,147]. The most common sites are the bowel wall, mesentery, shoulder girdle, chest wall, and extremities. Currently, first-line treatment involves wide local excision followed by chemotherapy, which, when considered alongside their high tendency for local recurrence, makes management a clinical challenge[142,148,149]. Application of minimally invasive ablation techniques provides an opportunity to manage unpredictable lesions in difficult to resect anatomical locations and in long-term management of recurrence.

RFA: RFA was first used in the treatment of desmoid tumors in a 2002 case report with no complications and no post-procedure recurrence[150]. Multiple additional case reports have demonstrated promising results with the use of RFA in both abdominal and extra-abdominal desmoid tumors[151-154]. To our knowledge, there has not yet been a formal RCT or other study to determine the survival benefit in the management of desmoid tumors with RFA. The proximity to and involvement with muscle tissue in desmoid tumor therapy presents a technical challenge with RFA treatment, as the electrical current needed for the procedure can stimulate contraction in local muscles. Unwanted muscle contractions can disrupt treatment accuracy and compromise safety, necessitating the use of pharmacologic muscle relaxants. Consequently, these medications exert a relaxation effect on the diaphragm, which typically requires the accompanied use of anesthesia and mechanical ventilation. This in turn adds complexity to the logistics of the procedure.

MWA: The only study to date of the use of MWA for desmoid fibromatosis treatment was conducted from 2010 to 2019 (n = 9 patients) and found an 88.9% response rate with an average tumor volume reduction of 70.4%[155]. To our knowledge, there have not yet been any formal studies investigating the survival statistics for MWA in desmoid tumors. A possible challenge could be low tissue response to microwaves due to the particular dielectric properties of desmoid tissue. This underscores the importance of considering the physical properties of the tissue targeted for ablation. These properties set limits on the suitability, predictability, reproducibility, and effectiveness of minimally invasive techniques[156].

CA: A retrospective study of 30 patients who underwent CT-guided CA for symptomatic desmoid tumors from 2007 to 2019 showed a response rate of 80%[157]. PFS at 1 and 3 years was found to be 85.1% and 77.3%, respectively. Complications occurred in 36.6% of cases and ranged from major complications of skin necrosis and infection (n = 4 patients) to minor complications of pain and self-resolving sensory neuropathy (n = 7 patients). Another study by a separate group reviewed cases of CT- or US-guided CA for non-abdominopelvic desmoid tumors from 2012 to 2020 (n = 84 patients) and found local tumor recurrence (n = 19/84 patients) to be associated anatomical location (lowest recurrence in abdominal wall vs highest in head and neck) and treatment history prior to CA[158]. Of note, the patients who had undergone prior surgical tumor debulking without adjuvant systemic therapy had higher disease recurrence that those who had undergone combination therapy. It is possible that in these cases of recurrence, the disruption of local anatomy during surgery may have led to unintended tumor seeding elsewhere in the body, which would be partially mitigated with systemic therapy post-op. PFS at 1, 2, and 3 years was found to be 89%, 74%, and 68%, respectively. Adverse events occurred in 21.4% of cases, primarily grade I in nature. CA may have a higher effectiveness in desmoid tumors compared to RFA or MWA since CA effect is not dependent on conductive or dielectric tissue properties.

HIFU ablation: A retrospective analysis of data from cases of desmoid tumor recurrence treated with low-power HIFU (n = 91 patients) calculated a response rate of 47.3% and a disease control rate of 96.7%[159]. Low-power HIFU was used in an effort to slow heat diffusion and mitigate collateral damage to adjacent tissue[160]. The estimated 5-year OS was calculated to be 69.3%. Several studies have investigated the efficacy of HIFU in the treatment of desmoid tumors and the feasibility of these treatments and found HIFU to provide significant and durable reduction in tumor and symptom burden with minimal complications[161-165]. To our knowledge there have not yet been formal studies of survival after HIFU treatment of desmoid tumors, though a clinical trial is currently ongoing to evaluate the use of HIFU in soft tissue sarcoma and desmoid tumors (clinicaltrials.gov identifier: NCT05111964). Desmoid tumors, while not metastatic, recur frequently and are locally aggressively invasive, which makes thermal ablative techniques like HIFU challenging to apply in complex anatomy, though this has been done successfully to date[163]. The current studies show the technique has promise for tumors distal to vital structures or for symptom control in recurrent disease; however, the need for acoustic access for techniques like RFA and HIFU creates limitations that must be considered when choosing a minimally invasive modality for this disease, especially when considered as an alternative to surgical resection or systemic therapy[51,166].

Histotripsy: As of this writing, the use of histotripsy in the treatment of desmoid tumors is still experimental, though its use has been demonstrated in a variety of other soft-tissue tumors[16,63,96]. With the growing use of HIFU in desmoid tumor treatment, the use of histotripsy for desmoid tumor therapy is theoretically feasible. The same limitations that exist for other US-based techniques also apply to histotripsy, further adding value to surmounting this technical obstacle. The ability to ablate tissue without relying on heat generation adds great potential to this technique for anatomically challenging masses as the thermal collateral damage to adjacent structures can be mitigated, if not altogether avoided.

FUTURE DIRECTIONS

The future of minimally invasive therapies for the treatment of solid tumors, including RFA, MWA, CA, HIFU, and histotripsy, promises significant advancements in safety, accuracy, predictability, and reproducibility. A critical area for future research is the comprehensive study of tumors not only from biochemical and biological perspectives, but also through the lens of materials science. Tumors possess distinct physical properties, such as thermal conductivity, dielectric properties, and mechanical stiffness, which can substantially influence the efficacy of various ablative modalities. Further exploration into the heterogeneous nature of tumors and considering factors such as vascularization, cellular density, and extracellular matrix composition will refine the precision of ablative treatments[167]. Understanding these physical characteristics will enable clinicians to select the most appropriate ablation technique tailored to a specific tumor type and its surrounding tissue architecture, thereby optimizing therapeutic outcomes and minimizing collateral damage to adjacent structures. A summary of some of the technical challenges and considerations necessary based on tumor location are presented in Table 3.

Table 3 Analysis of ablation techniques in specific anatomic locations.

Tumor location	Ablation technique	Technical challenges	Special considerations	Clinical outcomes
Liver	RFA, MWA, CA, HIFU, histotripsy	Proximity to major blood vessels, risk of bile duct injury/fistula	Need for real-time imaging guidance (universal consideration), risk of incomplete ablation	High response rate for small tumors, varies with tumor size and location
Lung	RFA, MWA, CA, experimental (HIFU, histotripsy)	Air-filled lung tissue provides poor acoustic access, risk of pneumothorax/effusion/fistula	Requirement for minimizing patient motion with respiration, use of adjunctive therapies to enhance efficacy	High technical success rate, varies with tumor size and location, high innovation to overcome acoustic access limitations
Kidney	RFA, MWA, CA, experimental (HIFU, histotripsy)	Proximity to adrenal gland, renal pelvis, and major blood vessels, risk of urinary tract injury	Need for careful post-procedural monitoring of vitals and chemistries	High technical success rate, lower recurrence with longer follow-up
Soft tissue	RFA, MWA, CA, HIFU, histotripsy	Involvement with muscle tissue, difficulty in achieving complete ablation without damaging surrounding structures, locally invasive	High recurrence rate, need for combination with systemic therapies and long-term management	High response rate in small studies, varies with tumor location and previous treatments, high success rate with disease burden reduction and quality of life improvement

RFA: Radiofrequency ablation; MWA: Microwave ablation; CA: Cryoablation; HIFU: High-intensity focused ultrasound.

Clinical trials have been instrumental in advancing minimally invasive tumor ablation, with the COLLISION trial standing as a landmark study. This trial demonstrated that thermal ablation could achieve outcomes equivalent to and more safely than surgical resection for small, resectable CRLM, challenging the long-held surgical standard of care. If widely implemented, these findings could revolutionize treatment approaches and possibly change the standard of care, offering life-saving therapy to patients previously deemed ineligible for surgery. Furthermore, the COLLISION trial has spurred follow-up studies, such as the COLLISION-XL and COLLISION RELAPSE trials, which aim to evaluate and compare thermal ablation and surgical resection in larger and recurrent CRLM. These trials hold the potential to reshape clinical practice further, broadening access to effective treatments for previously challenging cases.

Another promising direction is the integration of artificial intelligence (AI) and machine learning algorithms in the ablation planning and execution process paired with advances in medical imaging. The development of new imaging modalities and techniques have improved our ability to diagnose malignancies earlier in the disease course and provide accurate image-guided therapy[168]. AI can aid in processing complex imaging data to generate detailed three-dimensional reconstructions of tumors and their surrounding anatomy, facilitating precise mapping of the tumor’s spatial characteristics, and enabling physicians to devise more effective ablation strategies. AI-driven software can simulate different ablation scenarios, predicting thermal spread and optimizing probe placement to achieve maximal tumor eradication with minimal impact on healthy tissue. Additionally, AI can assist in real-time monitoring and adjustment during ablation procedures by analyzing feedback from imaging modalities such as MRI or US, allowing AI algorithms to provide intraoperative guidance and dynamically adjust parameters to enhance ablation precision.

Minimally invasive locoregional ablative techniques offer significant benefits to patients who are not surgical candidates or those presenting with advanced/recurrent disease[73]. Procedures that can be performed on an outpatient basis reduce the need for extensive excision and debulking of complex or multifocal lesions. This is particularly advantageous when balancing the risks of surgery and length of convalescent time to maximize surgical benefit. Outpatient or minimally invasive ablation decreases procedural morbidity and allows clinicians to implement a stepwise treatment strategy. While it may not be feasible to remove an entire large or multifocal tumor in a single session, locoregional ablation techniques enable staged treatments, reducing the tumor’s association with vital vasculature or neurologic structures and mitigating mass effect. This approach can make tumors more amenable to further ablation, offering a safer and more manageable alternative to traditional surgical resection.

CONCLUSION

Minimally invasive locoregional ablative therapies have revolutionized the treatment landscape for solid organ tumors and provide viable alternatives to traditional surgical approaches. Techniques such as RFA, MWA, CA, HIFU, and histotripsy have demonstrated significant efficacy in targeting and destroying malignant tissues with reduced morbidity and cost compared to surgical resection. These therapies offer both curative and palliative options, improving quality of life and survival outcomes for patients. Moreover, they present an invaluable opportunity for patients who are not candidates for traditional surgery or systemic therapies, allowing for tumor burden reduction, relief of symptoms, and overall enhancement of quality of life. By mitigating tumor burden and alleviating symptoms, these therapies can also improve patients’ physical fitness, potentially rendering them suitable for future surgical or systemic treatments. This stepwise approach enables clinicians to manage complex or multifocal tumors progressively, reducing the risk associated with extensive surgical interventions and facilitating more effective, personalized oncologic care.

Despite the significant advancements, the application of these therapies requires careful consideration of tumor type, size, location, and other patient-specific factors. Even use of advanced imaging guidance, while leading to improved outcomes, involves specialized equipment, software, and expertise, which reduces accessibility. Continued research and technical innovation are essential to overcoming current limitations and expanding the therapeutic potential of these modalities. Future directions include the integration of advanced imaging techniques, predictive models and intraoperative real-time data analysis, and combination therapies with systemic treatments such as chemo/immunotherapy. The evolution of minimally invasive tumor ablation holds promise for more effective, personalized cancer care. As clinical evidence continues to accumulate, these therapies are expected to become integral components of comprehensive cancer management strategies, ultimately improving patient outcomes and reducing the global burden of solid organ tumors.