Follow-up of vascular-targeted photodynamic therapy in a real-world setting.

PURPOSE: Vascular-targeted photodynamic therapy (VTP) is an approved treatment option for unilateral low-risk prostate cancer (PCa). METHODS: Patients with unilateral low- or intermediate-risk PCa undergoing hemiablation by VTP were evaluated in a real-world setting. Oncological outcome after VTP was measured by MRI-based re-biopsy at 12 and 24 months. Functional outcome after 1 year was investigated by IIEF-5 and IPSS questionnaires. Progression was defined as the evidence3 of ISUP ≥ 2 PCa. RESULTS: At any control biopsy (n = 46) after VTP, only 37% of patients showed no evidence of PCa. Recurrence-free survival was 20 months (95% CI 4.9-45.5) and progression-free survival was 38.5 months (95% CI 33.5-43.6 months). In-field and out-field recurrent PCa occurs in 37% (55% ISUP ≥ 2 PCa) and 35% (56% ISUP ≥ 2 PCa). Seventy-nine percent of patients preserved erectile function, respectively. Ten percent of patients presented long-term bladder outlet obstruction. None of the patients presented incontinence. CONCLUSION: Due to the high-recurrence in- and out-field recurrence rate in a mainly low-risk prostate cancer cohort, VTP has to be regarded critically as a therapy option in these patients. Pre-interventional diagnostic evaluation is the main issue before focal therapy to reduce the risk of tumor recurrence and progression.

Triggers and oncologic outcome of salvage radical prostatectomy, salvage radiotherapy and active surveillance after focal therapy of prostate cancer.

PURPOSE: Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies. METHODS: Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan-Meier curves were generated to determine oncological outcomes. RESULTS: A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9-16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35-4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort. CONCLUSION: With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.

Do contemporary imaging and biopsy techniques reliably identify unilateral prostate cancer? Implications for hemiablation patient selection.

BACKGROUND: Hemiablation is a less morbid treatment alternative for appropriately selected patients with unilateral prostate cancer (PCa). However, to the authors' knowledge, traditional diagnostic techniques inadequately identify appropriate candidates. In the current study, the authors quantified the accuracy for identifying hemiablation candidates using contemporary diagnostic techniques, including multiparametric magnetic resonance imaging (mpMRI) and MRI-fusion with complete systematic template biopsy. METHODS: A retrospective analysis of patients undergoing MRI and MRI-fusion prostate biopsy, including full systematic template biopsy, prior to radical prostatectomy in a single tertiary academic institution between June 2010 and February 2018 was performed. Hemiablation candidates had unilateral intermediate-risk PCa (Gleason score [GS] of 3+4 or 4+3, clinical T classification ≤T2, and prostate-specific antigen level <20 ng/dL) on MRI-fusion biopsy and 2) no contralateral highly or very highly suspicious Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) MRI lesions. Hemiablation candidates were inappropriately selected if pathologists identified contralateral GS ≥3+4 or high-risk ipsilateral PCa on prostatectomy. The authors tested a range of hemiablation inclusion criteria and performed multivariable analysis of preoperative predictors of undetected contralateral disease. RESULTS: Of 665 patients, 92 met primary hemiablation criteria. Of these 92 patients, 44 (48%) were incorrectly identified due to ipsilateral GS ≥3+4 tumors crossing the midline (21 patients), undetected distinct contralateral GS ≥3+4 tumors (20 patients), and/or ipsilateral high-risk PCa (3 patients) on prostatectomy. The rate of undetected contralateral disease ranged from 41% to 48% depending on inclusion criteria. On multivariable analysis, men with anterior index tumors were found to be 2.4 times more likely to harbor undetected contralateral GS ≥3+4 PCa compared with men with posterior lesions (P < .05). CONCLUSIONS: Clinicians and patients must weigh the risk of inadequate oncologic treatment against the functional benefits of hemiablation. Further investigation into methods for improving patient selection for hemiablation is necessary.

Hemiablation of Localized Prostate Cancer by High-Intensity Focused Ultrasound: A Series of 35 Cases.

Prostate cancer (PrC) is one of the most common tumors diagnosed in men. The detection rate of localized PrC has been dramatically enhanced by screening and the development of visualization methods. There are currently several techniques for focal treatment available, among which the most interesting in our opinion is high-intensity focused ultrasound (HIFU). Currently, HIFU hemiablation of PrC is not an established treatment, although evidence of its effectiveness and safety is growing. We have been performing HIFU hemiablation since 2013 and here report our results to add to the evidence on the effectiveness of the technique. Between October 2013 and December 2016, we performed HIFU hemiablation of the prostate for a total of 35 patients with confirmed PrC stage

Combination of multiparametric magnetic resonance imaging and transrectal ultrasound-guided prostate biopsies is not enough for identifying patients eligible for hemiablative focal therapy for prostate cancer.

PURPOSE: To evaluate focal therapy (hemiablation) eligibility in men undergoing prostate biopsy and multiparametric magnetic resonance imaging (mpMRI) with reference to histopathology from radical prostatectomy (RP) specimens. METHODS: Subjects were selected among 810 men who underwent prostate biopsy, mpMRI, and RP from January 2016 to December 2017. Hemiablation eligibility criteria were biopsy-proven unilateral cancer, prostate-specific antigen ≤ 15 ng/ml, and Gleason score (GS) ≤ 3 + 4. Evidence of non-organ-confined disease or Prostate Imaging Reporting and Data System score ≥ 4 on the contralateral lobe on mpMRI was classified as ineligible for hemiablation. Of the 810, data for 185 who met the screening criteria were compared to final pathology findings. Significant cancer at RP was defined as any of the following: (1) GS 6 with tumor volume ≥ 0.5 ml; (2) GS ≥ 3 + 4; or (3) the presence of advanced stage (≥ pT3). RESULTS: Among the 185 candidates for hemiablation, 62 (33.5%) had unilateral cancer on final RP histopathology. Among the 123 bilateral cancers, 50 (27%) were organ confined and had GS ≤ 3 + 4 = 7 and bilateral multifocal tumor in which the index tumor was confined to one lobe and the secondary tumor in the contralateral lobe had tumor volume < 0.5 ml and GS ≤ 6. A total of 112 (60.5%) patients in this series were considered suitable for hemiablation. Significant cancer on biopsy and mpMRI-negative lobes were found in 72 (38.9%) of 185 lobes, including 1 (0.5%) with advanced stage. CONCLUSIONS: The combination of standard prostate biopsy and mpMRI did not accurately identify lobes that could be considered as non-treated regions.

Salvage Hemiablation High Intensity Focused Ultrasound for unilateral radio-recurrent prostate cancer.

OBJECTIVE: To report the oncological and functional outcomes of salvage hemiablation high-intensity focused ultrasound (HIFU) in patients with unilateral radio-recurrent prostate cancer. PATIENTS AND METHODS: Patients with biochemical recurrence (BCR) after primary radiation therapy and evidence of unilateral organ confined recurrence based on a complete match between mpMRI and MRI targeted biopsies were included. Patients with distant metastasis were excluded. Patients were followed with serial serum PSA determinations. BCR were defined using the Phoenix criteria. Complications were graded according to the Clavien score. IIEF-5 questionnaire was used to assess erectile dysfunction. Urinary incontinence was reported using physician reported rates. RESULTS: A total of 10 consecutive patients (median age: 71 years, IQR: 69-76) were prospectively enrolled. The median pre-treatment PSA and post-treatment PSA nadir were 3.1ng/mL (IQR: 1.54-8.59) and 1.52ng/mL (IQR: 0.76-2.2), respectively. At a median follow-up of 41.5 (IQR: 18-58) months, 50% of patients experience BCR. BCR free-survival rates at 24 and 36 months were 75% (CI95%: 31-93) and 60% (CI95%: 20-85), respectively. Urinary in continence grade II occurred in two patients and the remaining patients were pad-free. One patient developed de novo erectile dysfunction requiring PDE5I. The erectile function scores decreased from a mean of 10.1 to 8.7. CONCLUSION: Hemiablation HIFU is an alternative to whole gland therapy in patients with unilateral radio- recurrent prostate cancer, which offers limited urinary and rectal morbidity, and preserves functional outcomes. LEVEL OF EVIDENCE: 3.

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients.

PURPOSE: We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR. RESULTS: A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48-82) years and 19 (6.3-38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725-24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100-1.422, p = 0.001] was independently associated with BCR. CONCLUSION: A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

Combination of multiparametric magnetic resonance imaging and transperineal template-guided mapping prostate biopsy to determine potential candidates for focal therapy.

Background: We assessed the ability of the combination of multiparametric magnetic resonance imaging (mpMRI) and transperineal template-guided mapping biopsy (TTMB) to determine the eligibility for focal therapy (FT) (hemiablation) in men and compared it with that of histology from radical prostatectomy (RP) specimens. Materials and methods: In this study, 120 men who underwent mpMRI, TTMB, and RP in a single tertiary center from May 2017 to June 2021 were analyzed. The criteria of hemiablation eligibility were unilateral low-to intermediate-risk prostate cancer (limited to a maximum of International Society of Urological Pathology (ISUP) grade group 3 and prostate-specific antigen (PSA) <20 ng/mL) and clinical stage ≤T2. Evidence of non-organ-confined disease or contralateral Prostate Imaging Reporting and Data System (PI-RADS) v2 score ≥4 on mpMRI was classified as ineligible for hemiablation. Clinically significant cancer at RP was defined as any of the following: (1) ISUP grade group 1 with tumor volume ≥1.3 mL; (2) ISUP grade group ≥2; or (3) the presence of advanced stage (≥pT3). Results: Of the 120 men, data of 52 men who met the selection criteria for hemiablation were compared with final RP findings. Of these 52 men, 42 (80.7%) could be considered suitable for hemiablation on RP. The sensitivity, specificity, and accuracy of mpMRI and TTMB in predicting FT eligibility were 80.7%, 85.1%, and 82.5%, respectively. The rate of undetected contralateral significant cancer was 10 (19.2%) on mpMRI and TTMB. Six had bilateral significant cancer and four had small volumes of ISUP grade group ≥2. Conclusions: The combination of mpMRI and TTMB substantially improves the prediction of potential candidates for hemiablation based on consensus recommendations. Improved selection criteria and further investigative tools are required to improve patient selection for hemiablation.

High-intensity focused ultrasound (HIFU) hemiablation of the prostate: Late follow-up MRI findings in non-recurrent patients.

OBJECTIVES: Focal therapy with high-intensity focused ultrasound (HIFU) is an emerging option for the treatment of prostate cancer and often followed up by MRI. Image assessment of treatment failure, however, requires proper knowledge about typical procedure-related changes in prostate MRI, which is sparse, in particular for unilateral HIFU treatment and late follow up (beyond 6 months). The goal of this study was therefore to compile the type and frequency of such MRI findings in selected patients without recurrent cancer 12 months after prostate hemiablation. METHODS: Data from a prospective multicenter trial on HIFU hemiablation were reviewed retrospectively. Trial patients have had a late follow-up by MRI (at around 12 months) and either MRI/transrectal ultrasound (TRUS) fusion or standard TRUS-guided biopsy. This work deliberately included patients with non-recurrent cancer in the treated prostate lobe in per-protocol biopsy leaving 30 men with initial International Society of Urological Pathology (ISUP) Grade Group of 1 or 2. Six categories of potential HIFU-related MRI features were assessed by an expert committee and then evaluated by two readers in consensus: 1. shrinkage of the treated lobe, 2. residual prostate tissue, 3. fluid-filled cavity, 4. fibrosis, 5. hematoma residuals (in the prostate or seminal vesicles) and 6. contrast enhancement of the ablated area. RESULTS: Shrinkage of the ablated lobe was seen in 93% of the cases with an average percent volume change of -37% (range: -70% to +108%). In the contralateral lobe, the volume remained practically the same (-2% on average, p = 0.804). In the ablated lobe, the frequency of fibrosis was 97%. Residual prostate tissue was seen in 93% of the cases. The frequency for fluid-filled cavities was 97%, with the wide majority (90%) contiguous with the urethra. Hematoma residuals in the prostate and in seminal vesicles were found in 47% and 10% of the patients, respectively. Contrast enhancement was both rim-like (50%) as well as diffuse (33%) within the ablated area. CONCLUSION: In our case series of HIFU hemiablation in the prostate, shrinkage, residual prostate tissue, fluid-filled cavities contiguous with the urethra and fibrosis were very common late MRI findings of the ablated lobe in non-recurrent patients. Rim-like contrast enhancement or diffuse one within the ablated area were less frequent.

Potential Candidates for Focal Therapy in Prostate Cancer in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Large Multicenter Cohort Study.

BACKGROUND: Focal therapy (FT) with its favorable side-effect profile represents an option between active surveillance and traditional whole-gland treatment in localized prostate cancer (PCa). Consensus statements recommend eligibility criteria based on magnetic resonance imaging (MRI)-targeted and systematic combination biopsy. OBJECTIVE: To estimate the future potential of FT by analyzing the number of men eligible for FT among all men with biopsy-proven PCa and to judge the potential of different energy sources. DESIGN, SETTING, AND PARTICIPANTS: Consensus criteria on FT were analyzed. Patients with biopsy-proven PCa from six tertiary referral hospitals and one outpatient practice in Germany had received a software-based combination biopsy. Men with Prostate Imaging Reporting and Data System (PI-RADS) ≥3 lesions based on PI-RADS v2 were included. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients were analyzed for potential treatment by FT and hemiablation. MRI lesions were mapped according to prostatic zones. RESULTS AND LIMITATIONS: In total, 2371 patients were analyzed. According to consensus criteria (biopsy-proven unifocal lesion of International Society of Urological Pathology [ISUP] grade group ≤2, prostate-specific antigen [PSA] ≤15ng/mL, and life expectancy >10yr), 303 patients (12.8%; ISUP 1: n=148 [6.2%]; ISUP 2: n=155 [6.5%]) were potential candidates for FT. A maximum PSA level of <10ng/mL would exclude further 60 (2.5%) of these men. The eligibility for hemiablation is slightly higher (16.2%). Unifocal lesions (n=288) were equally distributed within the prostate (anteriorly [31%], apically [29%], and dorsally [36%]). CONCLUSIONS: With adherence to consensus statements, only a minority of PCa patients present as potential candidates for FT. Distribution of tumor localization suggests the need for different energy modalities to warrant an optimal FT treatment. PATIENT SUMMARY: We analyzed how many men who receive a magnetic resonance imaging-targeted and systematic prostate biopsy are candidates for the experimental focal therapy of the prostate. When following expert recommendations, only a small number of men are potential candidates for this alternative treatment.