Sir Peter MacCallum Department of Oncology - Research Publications
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ItemModern paradigms for prostate cancer detection and management(WILEY, 2022-10-17)Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.
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ItemImpact of Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in the Management of Oligometastatic Renal Cell Carcinoma(ELSEVIER, 2022-10)BACKGROUND: Prostate-specific membrane antigen (PSMA) is overexpressed in the neovasculature of renal cell carcinoma (RCC). However, there remains limited evidence regarding the use of PSMA positron emission tomography/computed tomography (PET/CT) in RCC. OBJECTIVE: To assess the impact of PSMA PET/CT in the management of metastatic RCC. DESIGN SETTING AND PARTICIPANTS: This was a retrospective review of patients who underwent PSMA PET/CT from 2014 to 2020 for restaging or suspected metastatic RCC in a tertiary academic setting. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Management plans before and after PSMA PET/CT were recorded. Impact was classified as high (change of treatment intent, modality, or site), medium (change in treatment method), or low. Secondary outcomes included the patient-level detection rate, PSMA PET/CT parameters, sensitivity, and comparison to CT and, if available, fluorodeoxyglucose (FDG) PET/CT. RESULTS AND LIMITATIONS: Sixty-one patients met the inclusion criteria, of whom 54 (89%) had clear cell RCC. PSMA-positive disease was detected in 51 patients (84%). For 30 patients (49%) there was a change in management due to PSMA PET/CT (high impact, 29 patients, 48%). In 15 patients (25%), more metastases were detected on PSMA PET/CT than on CT. The sensitivity of combined PSMA PET/CT and diagnostic CT was 91% (95% confidence interval 77-98%). In a subcohort of 40 patients, the detection rate was 88% for PSMA and 75% for FDG PET/CT (p = 0.17). The maximum standardised uptake value (SUVmax) was higher for PSMA than for FDG PET/CT (15.2 vs 8.0; p = 0.02). Limitations include selection bias due to the retrospective design, and a lack of corresponding histopathology for all patients. CONCLUSIONS: PSMA PET/CT is a promising imaging modality in metastatic RCC and led to a change in management in 49% of patients. PSMA PET/CT detected additional metastases compared to CT in 25% of patients and registered a significantly higher SUVmax than FDG PET/CT. Prospective studies are required to further define its role. PATIENT SUMMARY: We report on a group of patients undergoing a new type of imaging for suspected advanced kidney cancer, called PSMA PET/CT. This imaging changed the management plan in 49% of the patients. PSMA PET/CT detected metastases in 84% of our patients and detected more metastases than computed tomography imaging in 25%.
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ItemCurrent treatment options for newly diagnosed metastatic hormone-sensitive prostate cancer-a narrative review(AME PUBL CO, 2021-10)Prostate cancer continues to be one of the most commonly diagnosed cancers in men globally and a leading cause of male cancer deaths. The landscape of metastatic hormone-sensitive prostate cancer has significantly changed over the past decade. For many years, androgen deprivation therapy alone through surgical or chemical castration was the mainstay of treatment yielding limited 5-year survival rates. New treatment approaches using Docetaxel chemotherapy or androgen receptor pathway inhibitors to intensify upfront systemic therapy have resulted in significantly improved survival rates compared to androgen deprivation therapy alone. Clinicians are now equipped with an arsenal of drugs capable of prolonging life for metastatic hormone-sensitive prostate cancer patients. Furthermore, new treatment modalities are being tested in clinical trials making treatment of metastatic hormone-sensitive prostate cancer an extremely dynamic space. In this narrative review, we provide an overview of the key systemic treatments for metastatic hormone-sensitive prostate cancer, namely androgen deprivation therapy, novel androgen receptor pathway inhibitors and Docetaxel. We summarise a series of landmark trials that have led to the integration of novel androgen receptor pathway inhibitors and docetaxel into the treatment paradigm for metastatic hormone-sensitive prostate cancer. Lastly, we discuss nursing, financial and side-effect considerations pertaining to the use of these drugs. This article aims to give its readers an understanding of the evidence and clinical aspects of novel therapies in metastatic hormone-sensitive prostate cancer as they become increasingly available for use around the world.
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ItemUnderstanding the diagnosis of prostate cancer(WILEY, 2020-11)Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men. Prostate-specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5-α reductase inhibitors such as dutasteride). Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%. International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasis ISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [< 10%] = 7) can be offered active surveillance. The goal of active surveillance is to defer treatment but is still curative when required. With better imaging (magnetic resonance imaging and emerging prostate-specific membrane antigen positron emission tomography-computed tomography) and transperineal prostate biopsy, more men can be offered screening after discussion of risks and benefits, knowing that overdiagnosis has been minimised and radical treatment is reserved for only the most aggressive disease.
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ItemA phase I/II study of stereotactic radiotherapy and pembrolizumab for oligometastatic renal tumours (RAPPORT): Clinical trial protocol(ELSEVIER INC, 2021-03)BACKGROUND: The management of oligometastatic clear cell renal cell carcinoma (ccRCC) varies widely, ranging from observation to resection or systemic therapies. Prolonged survival has been observed following resection or stereotactic ablative body radiotherapy (SABR). Immunotherapy combinations have shown survival benefits, however, toxicity is higher than that for monotherapy and complete response rates remain less than 10%. The combination of effective local therapies in conjunction with immunotherapy may provide more durable control and pre-clinical models have suggested a synergistic immune-priming effect of SABR. OBJECTIVES: and Methods: RAPPORT is a prospective, single arm, phase I/II study assessing the safety, efficacy and biological effects of single fraction SABR followed by pembrolizumab for oligometastatic ccRCC. The study will include 30 patients with histological confirmed ccRCC and 1-5 oligometastases, one or more of which must be suitable for SABR. Patients can have received prior systemic therapy but not prior immunotherapy. A single 20Gy of SABR is followed 5 days later by 8 cycles of 200 mg pembrolizumab, every 3 weeks. Adverse events are recorded using CTCAE V4.03 and tumour response evaluated by Response Evaluation Criteria in Solid Tumours version 1.1 (RECIST 1.1). Tumour tissue and peripheral blood samples will be collected pre-, during and post-treatment to assess longitudinal changes in immune subsets. OUTCOMES AND SIGNIFICANCE: The RAPPORT study will provide important safety and early efficacy data on the combination of SABR and pembrolizumab in oligometastatic ccRCC and will provide an insight into the underlying biological effects of combination therapy. TRIAL REGISTRATION: clinicaltrials.gov ID NCT02855203.
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ItemSafety first: evidence for delay of radical prostatectomy without use of androgen deprivation therapy during COVID-19(FUTURE MEDICINE LTD, 2020-07)