Intratumoural immunotherapy plus focal thermal ablation for localized prostate cancer.

Major advances have been made in the use of immunotherapy for the treatment of solid tumours, including the use of intratumourally injected immunotherapy instead of systemically delivered immunotherapy. The success of immunotherapy in prostate cancer treatment has been limited to specific populations with advanced disease, which is thought to be a result of prostate cancer being an immunologically 'cold' cancer. Accordingly, combining intratumoural immunotherapy with other treatments that would increase the immunological heat of prostate cancer is of interest. Thermal ablation therapy is currently one of the main strategies used for the treatment of localized prostate cancer and it causes immunological activation against prostate tissue. The use of intratumoural immunotherapy as an adjunct to thermal ablation offers the potential to elicit a systemic and lasting adaptive immune response to cancer-specific antigens, leading to a synergistic effect of combination therapy. The combination of thermal ablation and immunotherapy is currently in the early stages of investigation for the treatment of multiple solid tumour types, and the potential for this combination therapy to also offer benefit to prostate cancer patients is exciting.

A Comprehensive Assessment of the Utility of Transperineal Template Prostate Mapping Biopsy: A 13-year Experience.

OBJECTIVE: To assess Duke's experience on the utility of transperineal template mapping biopsy (TTMB) for re-evaluating patients with persistently elevated prostate-specific antigen after prior negative biopsy, with pre-existing prostate cancer (PCa) already on active surveillance (AS), or considering focal therapy (FT). METHODS: We retrospectively reviewed Duke patients undergoing TTMB. Functional outcomes were evaluated using International Index of Erectile Function-5 (IIEF-5) and International Prostate Symptom Score (IPSS). Complications within 30 days were recorded. Nonparametric statistical analyses compared functional measures from baseline to 2 and 6 weeks post-TTMB. RESULTS: From 8/2009 to 1/2021, 218 patients underwent TTMB, with 57-month median follow-up. Complication rate was 17.4%, with the majority Clavien I. Overall PCa detection was 72.9%, with clinically significant PCa in 53.2%; for those without prior PCa diagnosis (n = 117), overall detection was 64.1% with clinically significant PCa in 49.5%. Of those on AS at TTMB (n = 86), 36 (41.8%) had Gleason upgrading. TTMB changed management for 59 (68.6%) patients, with 38 (44.2%) proceeding to whole-gland therapy and 21 (24.4%) electing FT. Regarding functional outcomes, IPSS were insignificantly different from baseline at 6 weeks (P = NS). Overall functional score impacts were minimal across subgroups; in groups with significant declines in IIEF-5, median score drops were ≤1 point and caused minimal/no movement in IIEF-5 scoring category. CONCLUSION: In this cohort, TTMB offered enhanced cancer detection with overall minimal impact to functional outcomes. We conclude from this comprehensive assessment that TTMB provides value to rule out PCa, prevent overtreatment of those that can remain on AS, evaluate FT candidacy, and identify those needing whole-gland management.

Initial Longitudinal Outcomes of Risk-Stratified Men in Their Forties Screened for Prostate Cancer Following Implementation of a Baseline Prostate-Specific Antigen.

PURPOSE: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. MATERIALS AND METHODS: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017-2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. RESULTS: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). CONCLUSIONS: Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination.

Structured approach to resolving discordance between PI-RADS v2.1 score and targeted prostate biopsy results: an opportunity for quality improvement.

BACKGROUND: Prostate multiparametric magnetic resonance imaging (mpMRI) can identify lesions within the prostate with characteristics identified in Prostate Imaging Reporting and Data System (PI-RADS) v2.1 associated with clinically significant prostate cancer (csPCa) or Gleason grade group (GGG) ≥ 2 at biopsy. OBJECTIVE: To assess concordance (PI-RADS 5 lesions with csPCa) of PI-RADS v2/2.1 with targeted, fusion biopsy results and to examine causes of discordance (PI-RADS 5 lesions without csPCa) with aim to provide a structured approach to resolving discordances and develop quality improvement (QI) protocols. METHODS: A retrospective study of 392 patients who underwent mpMRI at 3 Tesla followed by fusion biopsy. PI-RADS v2/2.1 scores were assigned to lesions identified on mpMRI and compared to biopsy results expressed as GGG. Positive predictive value (PPV) of PI-RADS v2/2.1 was calculated for all prostate cancer and csPCa. Discordant cases were re-reviewed by a radiologist with expertise in prostate mpMRI to determine reason for discordance. RESULTS: A total of 521 lesions were identified on mpMRI. 121/521 (23.2%), 310/524 (59.5%), and 90/521 (17.3%) were PI-RADS 5, 4, and 3, respectively. PPV of PI-RADS 5, 4, and 3 for all PCa and csPCa was 0.80, 0.55, 0.24 and 0.63, 0.33, and 0.09, respectively. 45 cases of discordant biopsy results for PI-RADS 5 lesions were found with 27 deemed "true" discordances or "unresolved" discordances where imaging re-review confirmed PI-RADS appropriateness, while 18 were deemed "false" or resolved discordances due to downgrading of PI-RADS scores based on imaging re-review. Adjusting for resolved discordances on re-review, the PPV of PI-RADS 5 lesions for csPCa was deemed to be 0.74 and upon adjusting for presence of csPCa found in cases of unresolved discordance, PPV rose to 0.83 for PI-RADS 5 lesions. CONCLUSION: Although PIRADS 5 lesions are considered high risk for csPCa, the PPV is not 100% and a diagnostic dilemma occurs when targeted biopsy returns discordant. While PI-RADS score is downgraded in some cases upon imaging re-review, a number of "false" or "unresolved" discordances were identified in which MRI re-review confirmed initial PI-RADS score and subsequent pathology confirmed presence of csPCa in these lesions. CLINICAL IMPACT: We propose a structured approach to resolving discordant biopsy results using multi-disciplinary re-review of imaging and archived biopsy strikes as a quality improvement pathway. Further work is needed to determine the value of re-biopsy in cases of unresolved discordance and to develop robust QI systems for prostate MRI.