Longitudinal MRI changes after focal therapy for prostate cancer: cryotherapy vs. microwave tissue coagulation

We have previously reported longitudinal MRI findings following focal cryotherapy and MTC therapy as modality-specific studies [15, 17]. Building on these investigations, the present study represents a direct comparison of MRI findings following cryotherapy and MTC therapy under standardized conditions over an extended period. The early post-treatment MRI findings (i.e., up to and including 12 months after therapy in this study) differed noticeably between cryotherapy and MTC therapy, while the late-stage findings (i.e., beyond 12 months) indicated common signal changes. Although both modalities demonstrated similar contrast enhancement patterns after treatment, the progression of these changes over time differed to some extent. These findings highlight both modality-specific and common MRI changes, as well as their chronological progression.

Cryotherapy is the second most widely used FT modality for prostate cancer worldwide after HIFU [6]. It is well established for prostate cancer and has been extensively studied in other organs, including the kidney and liver. In contrast, MTC has been widely used for liver tumors but has only recently been applied for prostate cancer, with our hospital playing a pioneering role in its clinical application [11]. The emerging use of MTC therapy provides a unique opportunity to explore its potential as a novel FT modality for localized prostate cancer.

Clinically, cryotherapy and MTC therapy have complementary actions, allowing for strategic use based on tumor location. Cryotherapy is contraindicated for tumors near the membranous urethra in view of the risk of injury to the external urethral sphincter muscle [18], whereas MTC therapy can be safely applied near the membranous urethra owing to its well-defined treatment boundary. Conversely, MTC therapy is unsuitable for tumors near the rectum because of the high risk of thermal damage [11]. However, once cryotherapy has started and the cryoprobe is fixed, the prostate and probes can be manually lifted away from the rectum to avoid injury—a technique known as the “prostate-lifted-up technique”, originally developed by Dr. Ukimura [20]. Selecting the appropriate lesion-targeted focal ablation therapy based on tumor location may improve the efficacy of treatment while reducing complications.

The differences in MRI findings between the two modalities can be attributed to their distinct underlying mechanisms. Cryotherapy disrupts cell membranes by forming ice crystals and inducing osmotic stress [21], which leads to marked hemorrhage and a strong inflammatory response that accelerates tissue repair [22, 23]. These biological effects are reflected in the early post-treatment MRI findings: marked hyperintensity on T1WI and hyperintensity on both T2WI and DWI, consistent with hemorrhage [15] and similar to findings in rabbit kidney models [24]. In contrast, MTC induces cell death as a result of protein denaturation caused by rapid heating and thermal fixation [25], which preserves cellular structures while causing limited inflammation and a different tissue repair profile [26, 27]. The slight hyperintensity on T1WI, heterogeneous hypointensity on T2WI, and mixed signal intensity on DWI in the early post-treatment period after MTC therapy likely correspond to varying degrees of necrosis [17], as reported in liver studies [28,29,30].

Linear T2 hyperintensity along the needle tract was observed only after MTC therapy and during the early post-treatment period. Pathological studies have consistently demonstrated tissue loss surrounding the needle tract after MTC therapy, which appears as hyperintense areas on T2WI [11, 31, 32]. Although this finding has no pathological significance, it serves as a useful marker for objectively identifying the needle placement site on MRI after treatment.

Rim enhancement was observed on DCE–MRI in the early post-treatment period and gradually disappeared over time; this feature was common after both treatments in this study. Rim enhancement has been attributed to formation of granulation tissue, an inflammatory response, and hyperemia at the periphery of the ablation zone [15,16,17]. In this study, internal enhancement on DCE–MRI was observed in only one case following cryotherapy. In renal cell carcinoma, post-cryotherapy enhancement has been reported to persist for up to 9 months, potentially reflecting residual vasculature within the ablation zone, transient inflammation, or tissue repair [33, 34]. A similar phenomenon may occur in the prostate, but further investigation is required.

In this study, both cryotherapy and MTC therapy resulted in T2WI hypointensity and loss of contrast enhancement in the late post-treatment period, consistent with post-treatment scar formation. This fibrosis-related endpoint was further quantified in the present study and found to have a similar median time to convergence for both treatments.

The findings of this study are consistent with previous reports indicating that FT induces both general post-treatment changes and energy-specific effects [13, 14]. To facilitate cross-modality comparison, representative mpMRI findings at 1–3 months and 6–12 months after each FT modality, including cryotherapy, MTC, HIFU, FLA, and IRE, are schematically summarized in Fig. 5 [15, 17, 35,36,37,38,39,40]. At 1–3-month post-treatment, mpMRI findings varied markedly according to treatment modality, likely reflecting differences in the extent of necrosis, inflammation, and hemorrhage. Rim enhancement, which was observed after all therapies except FLA, likely reflects common tissue responses similar to those seen after cryotherapy and MTC [38, 41, 42]. At 6–12-month post-treatment, MRI findings often included T2 hypointensity across all FTs, consistent with treatment-induced fibrosis. In HIFU-treated cases, persistent subtle enhancement associated with chronic inflammation and fluid cavities communicating with the urethra has been reported [36]. In FLA-treated lesions at 12 months, ablation sites were mostly undetectable on DCE–MRI, with enhancement similar to that of the surrounding peripheral zone [37].

Fig. 5figure 5

Timeline showing typical multiparametric magnetic resonance imaging findings according to focal therapy modality for prostate cancer. This schematic diagram presents representative mpMRI features at 1–3 months and 6–12 months after the following five focal therapy modalities: HIFU, FLA, IRE, cryotherapy, and MTC. Imaging findings are shown across four MRI sequences: T1WI, T2WI, DWI, and DCE–MRI. The summary is based on previously published studies and our institutional experience with cryotherapy and MTC and aims to facilitate cross-modality comparison and clinical interpretation of post-treatment MRI changes. ADC apparent diffusion coefficient, DCE dynamic contrast enhancement, DWI diffusion-weighted imaging, FLA focal laser ablation, HIFU high-intensity focused ultrasound, IRE irreversible electroporation, MRI magnetic resonance imaging, MTC microwave tissue coagulation, NR not reported, T1WI T1-weighted imaging, T2WI T2-weighted imaging

The findings of this study clarify the differences in post-treatment MRI findings between cryotherapy and MTC therapy and may provide a reference for clinical evaluation. For example, following cryotherapy, marked hemorrhagic changes are often observed at 3-month post-treatment, and transient internal enhancement may also be present. These features could make it difficult to differentiate normal post-treatment changes from a residual or recurrent tumor, suggesting that assessment may become more reliable at approximately 6 months. In contrast, MTC therapy is less likely to show significant hemorrhagic changes or internal enhancement at 3 months. However, at this timepoint, DWI frequently shows a mixed signal pattern. By 6 months, hypointensity patterns become more predominant, yet mixed signal patterns can still be observed. In such instances, distinguishing small areas of high signal from residual tumor may be challenging, and careful interpretation is required.

This study has several limitations. First, it was performed retrospectively and included limited sample sizes, particularly for patients who received cryotherapy and those who underwent long-term follow-up after MTC therapy, where only a few patients were followed beyond 2 years. In the MTC group, patient numbers decreased over time, with < 50% undergoing MRI at the latest follow-up points. This limited long-term follow-up should be considered when interpreting the longitudinal imaging findings. However, the imaging findings generally stabilized in the late post-treatment period as a consequence of scar formation. Second, the study did not include a direct correlation of pathological results with imaging findings. Given that FT is a minimally invasive approach, routine pathological validation is not feasible in clinical practice. Prostatectomy for confirmation is not a viable option, making histopathological assumptions reliant on previously reported animal studies. Third, this study did not assess tumor recurrence either within the treated field (infield) or in untreated areas (outfield). However, the primary aim was to characterize the normal evolution of imaging findings after FT. Future research should investigate the MRI characteristics indicative of recurrence infield and those suggestive of a new lesion outfield following FT.

In conclusion, this research provides a direct comparison of MRI findings following cryotherapy with those after MTC therapy for localized prostate cancer. While early post-treatment MRI findings differed markedly between the two treatments, both ultimately led to similar fibrosis-related changes in the late phase. These insights should improve the interpretation of post-treatment MRI findings, help to optimize patient management, and may contribute to the development of standardized MRI follow-up protocols for FT.

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