Prostate cancer

An elevated serum PSA is a first sign of relapse and imaging is needed to determine the localisation of the recurrence, which may be locally in the prostatic area and/or metastatic. The precise localisation of the local recurrence by imaging is needed if this localisation could change treatment planning. Treatment for prostate cancer can significantly change the appearance of the residual prostate gland or the prostate bed, complicating imaging evaluation. It’s necessary to discern post-therapy changes from local recurrence. An overview of current imaging procedures and their performance in local recurrent PCa will be done, focusing on mpMRI. Therefore, mpMRI protocol (consists of T2W images, DWI/ADC and DCE-MRI) and evaluation of the images require specific considerations based on treatment received. For this reason, a standardised method of image assessment is needed to help in image analysis and reporting and to diminish variation in the acquisition, interpretation and reporting of prostate mpMRI in case of local recurrence. The relationships with PSA values will be also discussed. MpMRI can be currently considered as the most reliable imaging biomarker to detect local PCa recurrence in patients with biochemical failure after RP, especially for those PSA values where PET/CT is not recommended (0.2 - 1 ng/mL).

Tumour relapse is an undesirable reality in all cancer patients, and short of minimising its occurrence by applying to optimal treatment modality at the time of diagnosis, the best outcomes are achieved by early detection of recurrence and prompt initiation of salvage therapies. Early detection on imaging is facilitated by understanding the expected post-treatment findings and learning common patterns of recurrence for different cancers. In this session, we will review the patterns of recurrence and multimodality imaging appearance of cancers involving the urinary system (kidneys, ureters, bladder).

Emerging techniques and new targets in nuclear medicine have enabled new therapeutic approaches following the very own concept of biomarker imaging and therapy. Performing imaging and therapy using identical biochemical structures and metabolic properties as targets are summarised with the portmanteau-word “theranostics”. But theranostics can be seen in a broader spectrum of applications, especially when focusing on diagnostics that lead to an impact on therapeutic decisions. This lecture will give an overview of biomarker imaging in urological cancer, that has a direct impact on therapeutic decisions as well as treatment with the same target structure focusing on prostate cancer. A prime example is given by the use of bone scintigraphy for Imaging osteoblastic activity which is targeted by 223RaCl2 therapy, proven to provide a survival benefit in castration-resistant prostate cancer patients. Beyond this, PSMA ligand positron emission tomography, as a specific method for imaging the folate hydrolase, has emerged as an almost routinely applied procedure in high-risk prostate cancer primary staging, biochemical recurrence and advanced tumour stages. Recent studies have proven its impact on therapeutic decisions in almost a third of the patients with primary disease and even 75% of the patients with biochemical recurrence who were negative on conventional imaging. Applying the direct theranostic approach in patients who underwent 177Lu-PSMA therapy (RLT), PSMA ligand PET response correlated with overall survival, overcoming the known issues of RECIST criteria. In summary, the theranostic approach enables a more personalised concept with highly specific therapeutic effect and low side effect profile.

Screening for prostate cancer with prostate-specific antigen (PSA) has been widely investigated. Several large screening studies, e.g. prostate, lung, colorectal and ovarian (PLCO), European randomised study of screening for prostate cancer (ERSPC) and cluster randomised trial of PSA testing (CAP), have shown PSA screening may lead to increased prostate cancer diagnoses, and at best may result in a small benefit in disease-specific mortality over 10 years but does not improve overall mortality. These benefits need to be considered against possible harms of PSA screening, including complications from a biopsy and subsequent treatments and the risk of overdiagnosis and treatment. Recent studies suggest incorporating MRI in the investigation of those with positive PSA test reduces the false positive rate and unnecessary biopsies and also increases the accuracy of biopsies in those with clinically significant cancer. Trials screening for prostate cancer with MRI is being proposed. Incorporating the patient’s genetic mutation status into risk algorithms may allow development of targeted screening programs for early cancer detection and treatment, and may improve survival. Those with germline mutations such as BRCA2 have an increased risk from the age of 40yrs, and often more aggressive disease. There is also ongoing work stratifying prostate cancer risk at a population level with the use of single nucleotide polymorphism (SNP) panels. This use of targeted PSA and MRI screening in men with DNA repair mutations, adverse SNP profile and Afro-Caribbean ethnicity may result in improved outcomes and management algorithms based on biological disease behaviour.

Screening for prostate cancer with prostate-specific antigen (PSA) has been widely investigated. Several large screening studies, eg prostate, lung, colorectal and ovarian (PLCO), European randomised study of screening for prostate cancer (ERSPC) and cluster randomised trial of PSA testing (CAP), have shown PSA screening may lead to increased diagnoses of prostate cancer and at best may result in a small benefit in disease-specific mortality over 10 years but does not improve overall mortality. These benefits need to be considered against the possible harms of PSA screening, including complications from a biopsy and subsequent treatments and the risk of overdiagnosis and treatment. Recent studies suggest incorporating MRI in the investigation of those with positive PSA test reduces false positive rate and patients undergoing unnecessary biopsies and also increases the accuracy of biopsies in those with clinically significant cancer.
Trials screening for prostate cancer with MRI is being proposed. Incorporating the patient’s genetic mutation status into risk algorithms may allow development of targeted screening programs for early cancer detection and treatment, and may improve survival. Those with germline mutations such as BRCA2 have an increased risk from the age of 40yrs, and often more aggressive disease. There is also ongoing work stratifying prostate cancer risk at a population level with the
use of single nucleotide polymorphism (SNP) panels. This use of targeted PSA and MRI screening in men with DNA repair mutations, adverse SNP profile and those of Afro-Caribbean ethnicity may result in improved outcomes and management algorithms based on biological disease behaviour.

In order to avoid unnecessary radical treatment, active surveillance (AS) is becoming a viable treatment alternative in low-risk prostate cancer. Because most low-risk prostate tumours have an indolent course and the slow growth rate allows ample time during follow-up to detect tumours that begin more aggressive while remaining in a window of definitive curability. Patients are carefully observed every three or four months for changes in PSA, digital rectal examination or changes upon performed transrectal ultrasound (TRUS) guided biopsy. MR imaging is an appealing imaging technique to select and to surveil patients who choose for active surveillance. The addition of prostate MR imaging to the biopsy strategy or, in select patients, using MR imaging as a substitute for a repeat biopsy improves prostate cancer detection.

The presentation first highlights the different time points in the course of prostate cancer (PCa) where imaging is needed, i.e. new diagnosis, biochemical recurrence and metastatic castration-resistant PCa. For each of these stages, the current standard of care and needs for modern imaging approaches are discussed. Whole body MRI technique is presented, with emphasis on the evolution of protocols and current minimal and optimal requirements. Examples are provided illustrating findings in the most frequently affected organs: bones and nodes. Anatomic and functional (DWI) sequences are introduced, and their respective roles and limitations are highlighted, by the time of lesion detection and for the assessment of response to treatment. A practical presentation of the Met Rads P system is provided, with emphasis on standardisation of acquisitions, reporting, quantitative evaluation of disease burden, and response assessment.

The availability of multiple life-prolonging agents for Advanced Prostate Cancer (APC), in conjunction with the inter- and intra-patient molecular heterogeneity of this disease, present major challenges for therapy selection and treatment switch decisions. In addition, the standard imaging in APC (CT and Bone Scans), are unable to provide objective criteria for assessing treatment response of bone metastases, the dominant site of metastatic disease in APC and the only site of involvement in 40-60% of APC patients. Earlier identification of treatment failure would avoid potential toxicity, reduce the costs of ineffective treatments and decrease the time to initiation of a next-line, potentially effective treatment. WBMRI has an improved performance compared to standard imaging in the detection of active bone metastases extent, it can identify early response to therapy without the confounder of FLARE, and it has the ability to identify mixed response to treatment, reflecting clonal disease evolution. WBMR-DWI strengths come from its wide availability, lack of radiation and the opportunity of performing a “one-stop shop examination” which can stage and assess response in local disease and in the bone, nodal and visceral metastases without routine contrast administration. Like any other new technique, there is ongoing development towards optimisation and standardisation both in terms of acquisition and data interpretation.

The introduction of the new PET Tracers targeting the prostate specific membrane antigen (PSMA) changed the approach in patients with biochemical recurrence after radical prostatectomy dramatically. With promising detection rates of 58% and 76% for PSA ranges of 0.2-1 ng/ml and 1-2 ng/ml, PSMA-PET surpasses all other imaging modalities and enables an early localisation of recurrent disease. For restaging prostate cancer PSMA-PET/CT is usually performed, with the CT component used for attenuation correction, localisation of the tracer activity (e.g. ureter vs lymph node) and characterisation of the lesions (e.g. sclerotic vs lytic bone lesions). Given the high sensitivity for metastasis in the recurrence situation, there is an increasing interest for PSMA-PET to stage primary high-risk cancers. With PSMA-PET/MRI not only the detection of metastasis but also the utility of PSMA-PET to improve the detection of primary prostate cancer is under investigation. First results showed an improved detection rate for significant prostate cancer with PSMA-PET/MRI compared to mpMRI. However, despite these promising results it is important to keep in mind that around 10% of the prostate cancers (low grade and high-grade tumours) are PSMA negative and therefore will not be detected with PSMA-PET. Furthermore, the term “prostate specific” is misleading. It is important to know that there are physiological structures (e.g. duodenum, kidneys) as well as neovasculature with high PSMA expression, leading to potential false positive lesions on PSMA-PET such as secondary primaries (e.g. lung cancer, renal cancer), hemangiomas or Padgett’s disease.