The Impact of Positron Emission Tomography Imaging and Tumor Molecular Profiling on Risk Stratification, Treatment Choice, and Oncological Outcomes of Patients with Primary or Relapsed Prostate Cancer: An International Collaborative Review of the Existing Literature.

CONTEXT: The clinical introduction of next-generation imaging methods and molecular biomarkers ("radiogenomics") has revolutionized the field of prostate cancer (PCa). While the clinical validity of these tests has thoroughly been vetted, their clinical utility remains a matter of investigation. OBJECTIVE: To systematically review the evidence to date on the impact of positron emission tomography (PET) imaging and tissue-based prognostic biomarkers, including Decipher, Prolaris, and Oncotype Dx, on the risk stratification, treatment choice, and oncological outcomes of men with newly diagnosed PCa or those with biochemical failure (BCF). EVIDENCE ACQUISITION: We performed a quantitative systematic review of the literature using the MEDLINE, EMBASE, and Web of Science databases (2010-2022) following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines. The validated Quality Assessment of Diagnostic Accuracy Studies 2 scoring system was used to assess the risk of bias. EVIDENCE SYNTHESIS: A total of 148 studies (130 on PET and 18 on biomarkers) were included. In the primary PCa setting, prostate-specific membrane antigen (PSMA) PET imaging was not useful in improving T staging, moderately useful in improving N staging, but consistently useful in improving M staging in patients with National Comprehensive Cancer Network (NCCN) unfavorable intermediate- to very-high-risk PCa. Its use led to a management change in 20-30% of patients. However, the effect of these treatment changes on survival outcomes was not clear. Similarly, biomarkers in the pretherapy primary PCa setting increased and decreased the risk, respectively, in 7-30% and 32-36% of NCCN low-risk and 31-65% and 4-15% of NCCN favorable intermediate-risk patients being considered for active surveillance. A change in management was noted in up to 65% of patients, with the change being in line with the molecular risk-based reclassification, but again, the impact of these changes on survival outcomes remained unclear. Notably, in the postsurgical primary PCa setting, biomarker-guided adjuvant radiation therapy (RT) was associated with improved oncological control: Δ↓ 2-yr BCF by 22% (level 2b). In the BCF setting, the data were more mature. PSMA PET was consistently useful in improving disease localization-Δ↑ detection for T, N, and M staging was 13-32%, 19-58%, and 9-29%, respectively. Between 29% and 73% of patients had a change in management. Most importantly, these management changes were associated with improved survival outcomes in three trials: Δ↑ 4-yr disease-free survival by 24.3%, Δ↑ 6-mo metastasis-free survival (MFS) by 46.7%, and Δ↑ androgen deprivation therapy-free survival by 8 mo in patients who received PET-concordant RT (level 1b-2b). Biomarker testing in these patients also appeared to be helpful in risk stratifying and guiding the use of early salvage RT (sRT) and concomitant hormonal therapy. Patients with high-genomic-risk scores benefitted from treatment intensification: Δ↑ 8-yr MFS by 20% with the use of early sRT and Δ↑ 12-yr MFS by 11.2% with the use of hormonal therapy alongside early sRT, while low-genomic-risk score patients did equally well with initial conservative management (level 3). CONCLUSIONS: Both PSMA PET imaging and tumor molecular profiling provide actionable information in the management of men with primary PCa and those with BCF. Emerging data suggest that radiogenomics-guided treatments translate into direct survival benefits for patients, however, additional prospective data are awaited. PATIENT SUMMARY: In this review, we evaluated the utility of prostate-specific membrane antigen positron emission tomography and tumor molecular profiling in guiding the care of men with prostate cancer (PCa). We found that these tests augmented risk stratification, altered management, and improved cancer control in men with a new diagnosis of PCa or for those experiencing a relapse.

Design of the PROstate cancer follow-up care in Secondary and Primary hEalth Care study (PROSPEC): a randomized controlled trial to evaluate the effectiveness of primary care-based follow-up of localized prostate cancer survivors.

BACKGROUND: In its 2006 report, From cancer patient to cancer survivor: lost in transition, the U.S. Institute of Medicine raised the need for a more coordinated and comprehensive care model for cancer survivors. Given the ever increasing number of cancer survivors, in general, and prostate cancer survivors, in particular, there is a need for a more sustainable model of follow-up care. Currently, patients who have completed primary treatment for localized prostate cancer are often included in a specialist-based follow-up care program. General practitioners already play a key role in providing continuous and comprehensive health care. Studies in breast and colorectal cancer suggest that general practitioners could also consider to provide survivorship care in prostate cancer. However, empirical data are needed to determine whether follow-up care of localized prostate cancer survivors by the general practitioner is a feasible alternative. METHODS: This multicenter, randomized, non-inferiority study will compare specialist-based (usual care) versus general practitioner-based (intervention) follow-up care of prostate cancer survivors who have completed primary treatment (prostatectomy or radiotherapy) for localized prostate cancer. Patients are being recruited from hospitals in the Netherlands, and randomly (1:1) allocated to specialist-based (N = 195) or general practitioner-based (N = 195) follow-up care. This trial will evaluate the effectiveness of primary care-based follow-up, in comparison to usual care, in terms of adherence to the prostate cancer surveillance guideline for the timing and frequency of prostate-specific antigen assessments, the time from a biochemical recurrence to retreatment decision-making, the management of treatment-related side effects, health-related quality of life, prostate cancer-related anxiety, continuity of care, and cost-effectiveness. The outcome measures will be assessed at randomization (≤6 months after treatment), and 12, 18, and 24 months after treatment. DISCUSSION: This multicenter, prospective, randomized study will provide empirical evidence regarding the (cost-) effectiveness of specialist-based follow-up care compared to general practitioner-based follow-up care for localized prostate cancer survivors. TRIAL REGISTRATION: Netherlands Trial Registry, Trial NL7068 (NTR7266). Prospectively registered on 11 June 2018.

Minimizing the number of implantation needles for prostate (125)I brachytherapy: an investigation of possibilities and implications.

PURPOSE: Reduction of the number of implantation needles for prostate brachytherapy will shorten the duration of implantation procedures and possibly reduce trauma-related morbidity. The purpose of this study was to investigate possibilities for the minimization of the number of needles and to investigate the consequences for the dose distribution. METHODS AND MATERIALS: A planning study for six different prostate volumes was performed. The number of needles was minimized by changing fixed 1cm interseed spacing to free interseed spacing within the needles and by increasing the seed activity. Dose-volume parameters of prostate and organs at risk (OAR) bladder, rectum, and urethra were determined. For plans with different needle and seed configurations, the sensitivity for random seed placement inaccuracies was tested. Dose distributions of realized implants based on fixed (n=21) and free interseed spacing (n=21) were compared. RESULTS: The average number of needles (±1 standard deviation) could be reduced from 18.8±3.6 to 12.7±2.9 (-33%) when changing from fixed interseed spacing to free interseed spacing and subsequently to 7.3±1.0 (-42%) by increasing the seed strength from 0.57U to 1.14U. These needle reductions resulted in increased dose inhomogeneity within the prostate and increased sensitivity of dose-volume parameters of the OAR for random geometrical inaccuracies. Introduction of free interseed spacing in our clinic resulted in very satisfactory dose coverage of the prostate (D(90)=172±17Gy), while the average number of needles was reduced by 30%. CONCLUSIONS: Substantial reduction of the number of implantation needles is possible without compromising adequate dose coverage of the prostate. However, the chance of an unpredicted high dose to the OAR increases as fewer needles are used.

The influence of geometrical changes on the dose distribution after I-125 seed implantation of the prostate.

PURPOSE: After prostate implantation, dose calculation is usually based on a single imaging session, assuming no geometrical changes occur during the months of dose accumulation. In this study, the effect of changes in anatomy and implant geometry on the dose distribution was investigated. MATERIALS AND METHODS: One day, 1 month and 312 months after seed implantation, a combined TRUS-CT scan was made of 13 patients. Based on these scans changes in dose rate distribution were determined in prostate, urethra and bladder and a 'geometry corrected' dose distribution was estimated. RESULTS: When based on the day-1 scan, parameters representing high dose volumes in prostate and urethra were largely underestimated: V150 of the prostate 18+/-10% and V120 of the urethra 47+/-32%. The dose to a 2cm(3) hotspot in the bladder wall (D2cc), however, was overestimated by 31+/-35%. Parameters based on scans 1 month post-implant or later were all within +/-5% of geometry corrected values. CONCLUSION: Values meant to indicate the adequacy of dose coverage of the prostate, V100 and D90, were not influenced by geometrical changes and were independent of the post-implant scan date. Other parameters representing high dose volumes changed strongly within the first month after implantation.