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Background

Thermal ablation (TA) with radiofrequency (RFA) or cryoablation (CA) are established treatments for small renal masses (≤4 cm). Microwave ablation (MWA) has several potential benefits (decreased ablation time, less susceptibility to heat-sink, higher lesion temperatures than RFA) but is still considered experimental considering the available small-sample studies with short follow-up.

Purpose

To evaluate technique efficacy and complications of our initial experience of renal tumors treated using percutaneous MWA with a curative intent.

Material and Methods

A total of 105 renal tumors (in 93 patients) were treated between April 2014 and August 2017. MWA was performed percutaneously with computed tomography (CT) guidance under conscious sedation (n=82) or full anesthesia. Patients were followed with contrast-enhanced CT scans at six months and yearly thereafter for a minimum of five years. The mean follow-up time was 2.1 years. The percentage of tumors completely ablated in a single session (primary efficacy rate) and those successfully treated after repeat ablation (secondary efficacy rate) were recorded. Patient and tumor characteristics as well as complications were collected retrospectively.

Results

The median patient age was 70 years and median tumor size was 25 mm. Primary efficacy rate was 96.2% (101/105 tumors). After including two residual tumors for a second ablation session, secondary efficacy was 97.1% (102/105). Periprocedural complications were found in 5.2% (5/95) sessions: four Clavien-Dindo I and one Clavien-Dindo IIIa. One postprocedural Clavien-Dindo II complication was found.

Conclusion

MWA has high efficacy rates and few complications compared to other TA methods at a mean follow-up of two years.

Background: Comparable oncological outcomes have been seen after surgical nephrectomy and thermal ablation of renal tumors recently. However, periprocedural outcome needs to be assessed for aiding treatment decision.

Purpose: To compare efficacy rates and periprocedural outcome (technical success, session time, hospitalization time, and complications) after renal tumor treatment with laparoscopic partial nephrectomy (LPN) or radiofrequency ablation (RFA).

Material and Methods: The initial experience with 49 (treated with LPN) and 84 (treated with RFA) consecutive patients for a single renal tumor (diameter ≤ 5 cm, limited to the kidney) during 2007-2014 was evaluated. Patient and tumor characteristics, efficacy rates, and periprocedural outcome were collected retrospectively. The stratified Mantel Haenzel and Van Elteren tests, adjusted for tumor complexity (with the modified R.E.N.A.L nephrometry score [m-RNS]), were used to assess differences in treatment outcomes.

Results: Primary efficacy rate was 98% for LPN and 85.7% for RFA; secondary efficacy rate was 93.9% for LPN and 95.2% for RFA; and technical success rate was 87.8% for LPN and 100% for RFA. Median session (m-RNS adjusted P < 0.001; LPN 215 min, RFA 137 min) and median hospitalization time were longer after LPN (m-RNS adjusted P < 0.001; LPN 5 days, RFA 2 days). Side effects were uncommon (LPN 2%, RFA 4.8%). Complications were more frequent after LPN (m-RNS adjusted P < 0.001; LPN 42.9%, RFA 10.7%).

Conclusion: Both methods achieved equivalent secondary efficacy rates. RFA included several treatment sessions, but session and hospitalization times were shorter, and complications were less frequent than for LPN. The differences remained after adjustment for renal tumor complexity.

BACKGROUND: Radiofrequency ablation (RFA) can be used to treat renal masses in patients where surgery is preferably avoided. As tumor size and location can affect ablation results, procedural planning needs to identify these factors to limit treatment to a single session and increase ablation success.

PURPOSE: To identify factors that may affect the primary efficacy of complete renal tumor ablation with radiofrequency after a single session.

MATERIAL AND METHODS: Percutaneous RFA (using an impedance based system) was performed using computed tomography (CT) guidance. Fifty-two renal tumors (in 44 patients) were retrospectively studied (median follow-up, 7 months). Data collection included patient demographics, tumor data (modified Renal Nephrometry Score, histopathological diagnosis), RFA treatment data (electrode placement), and follow-up results (tumor relapse). Data were analyzed through generalized estimating equations.

RESULTS: Primary efficacy rate was 83%. Predictors for complete ablation were optimal electrode placement (P = 0.002, OR = 16.67) and increasing distance to the collecting system (P = 0.02, OR = 1.18). Tumor size was not a predictor for complete ablation (median size, 24 mm; P = 0.069, OR = 0.47), but all tumors ≤2 cm were completely ablated. All papillary tumors and oncocytomas were completely ablated in a single session; the most common incompletely ablated tumor type was clear cell carcinoma (6 of 9).

CONCLUSION: Optimal electrode placement and a long distance from the collecting system are associated with an increased primary efficacy of renal tumor RFA. These variables need to be considered to increase primary ablation success. Further studies are needed to evaluate the effect of RFA on histopathologically different renal tumors.

Background: While the optimal use and timing of secondary therapy after radical prostatectomy (RP) remain controversial, there are limited data on patient-reported outcomes following multimodal therapy.

Objective: To assess the impact of additional radiation therapy (RT) and/or androgen deprivation therapy (ADT) on urinary continence, potency, and quality of life (QoL) after RP.

Design, setting, and participants: Among 13 150 men who underwent RP from 1992 to 2013, 905 received RP + RT, 407 RP + ADT and 688 RP + RT + ADT.

Outcome measurements and statistical analyses: Urinary function, sexual function, and overall QoL were evaluated annually using self-administered validated questionnaires. Propensity score-matched and bootstrap analyses were performed, and the distributions for all functional outcomes were analyzed as a function of time after RP.

Results and limitations: Patients who received RP + RT had a 4% higher overall incontinence rate 3 yr after surgery, and 1% higher rate for severe incontinence (> 3 pads/24 h) compared to matched RP-only patients. ADT further increased the overall and severe incontinence rates by 4% and 3%, respectively, compared to matched RP + RT patients. RP + RT was associated with an 18% lower rate of potency compared to RP alone, while RP + RT + ADT was associated with a further 17% reduction compared to RP + RT. Additional RT reduced QoL by 10% and additional ADT by a further 12% compared to RP only and RP + RT, respectively. The timing of RT after RP had no influence on continence, but adjuvant compared to salvage RT was associated with significantly lower potency (37% vs 45%), but higher QoL (60% vs 56%). Limitations of our study include the observational study design and potential for selection bias in the treatments received.

Conclusions: Secondary RT and ADT after RP have an additive negative influence on urinary function, potency, and QoL. Patients with high-risk disease should be counseled before RP on the potential net impairment of functional outcomes due to multimodal treatment.

Patient summary: Men with high-risk disease choosing surgery upfront should be counseled on the potential need for additional radiation and or androgen deprivation, and the potential net impairment of functional outcomes arising from multimodal treatment.

Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

Active surveillance (AS) for prostate cancer was introduced to address overtreatment resulting from prostate-specific antigen (PSA) testing. Despite advancements such as Magnetic Resonance Imaging (MRI) and targeted biopsies, PSA remains crucial in prostate cancer diagnostics, leading to ongoing challenges of overdiagnosis and overtreatment. This thesis aimed to investigate different aspects of AS and follow-up of early prostate cancer and provide new insights to reduce overtreatment and enhance surveillance and follow-up. In Paper I, the rationale and methodology of a randomized controlled trial, the Prostate Cancer Active Surveillance Trigger trial/Scandinavian Prostate Cancer Group study no. 17 (PCASTt/SPCG17), were outlined. This trial's objective is to evaluate the safety of an AS protocol based on MRI and standardized triggers for repeat biopsies and transition to radical treatment. Patient recruitment is anticipated to conclude in 2024. Paper II investigated the risks of biochemical recurrence, metastatic disease, and prostate cancer-related death in patients following radical prostatectomy. The analysis was conditioned on time after radical prostatectomy without biochemical recurrence. For patients with favourable histopathology in prostatectomy specimens and no biochemical recurrence five years post-prostatectomy, the probability of developing metastatic disease or dying from prostate cancer within 20 years after surgery was very low. This suggests shorter follow-up for selected patients. Paper III compared outcomes of AS for men from different healthcare regions in Sweden with varying traditions of AS. Regions with lower uptake in AS demonstrated a higher probability of transitioning from AS to radical treatment, but no difference in AS failure. The results suggest overtreatment in regions with low uptake in AS. Paper IV explored the associations between potential triggers for transitioning from AS to radical treatment and the transition to treatment. We analysed how this association changed with the introduction of prostate MRI. We found an increasingly strong association between triggers, particularly histopathological progression, and transition. However, most treated men had not experienced histopathological progression. The introduction of MRI did not contribute much to the change. In conclusion, this thesis outlines an ongoing study on defined triggers for transitioning from AS to radical treatment, suggests shorter follow-up after radical prostatectomy for selected patients, reveals overtreatment in regions with low uptake in AS, and shows an increasing use of histopathological progression as a trigger for transition to radical treatment.