Fibroblast activation protein (FAP) is overexpressed in the tumor microenvironment or stroma of over 90% of solid tumors, what makes it a promising target for both therapeutic and molecular imaging applications. FAP-targeting molecular imaging has been quickly gaining steam in cancer diagnostics. It is especially useful for tumors with a strong desmoplastic (forming fibrous tissue) reaction, such as breast, colon, and pancreatic cancers.
Effectiveness of 177Lu-PSMA without prior chemotherapy
Since the end of the VISION trial that proved 177Lu-PSMA to be an effective treatment of metastasized prostate cancer, the next question arose – does it work even better if applied earlier in the course of the disease? An exciting study has now demonstrated that 177Lu-PSMA applied prior to chemotherapy is indeed more effective.
The metaanalysis was designed to evaluate the impact of prior taxane chemotherapy on response and survival in mCRPC patients after 177Lu-PSMA RLT.
It pooled together 13 studies comprising 2.068 patients. The results were:
- Taxane-naïve patients had 1,82 times better odds of biochemical response, i.e. 1,8 higher chances of no PSA rise.
- Taxane-naïve status was a predictor of both: significantly better progression-free survival (over 40%) and overall survival (over 46%).
Another clinical trial underway looks at the effectiveness of 177Lu-PSMA RLT in parallel with the anti-hormonal Androgen Deprivation Therapy. Results are expected in Q3 2024.
Personalized targeted radioligand therapy is complex and time-sensitive
Manufacturing radioligands is an extremely complex and time-sensitive process, because radiopharmaceuticals need to be “delivered” directly to the cancer cells within days after being synthesized. This is what personalized targeted radionuclide therapy, a game-changer in oncology, is all about. Having our own laboratory and highly proficient radiochemists helps us serve our patients in-time and with the highest possible flexibility.
Dual-Tracer PET-MRI-Derived Imaging Biomarkers for Prediction of Clinically Significant Prostate Cancer
Some prostate cancer cases will never develop metastases or any clinical symptoms and are defined as clinically insignificant. Accurate diagnosis able to differentiate between clinically significant and insignificant lesions leads to better disease management. The latest research of our working group has demonstrated that combined hybrid imaging using [18F] fluoromethylcholine (FMC) PET and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-PET achieved higher sensitivity for detecting clinically significant prostate cancer compared to multiparametric MRI alone. The PSMA PET is the leading method in this hybrid approach and is in fact more reliable than MRI alone.
As many trials with 177Lu-PSMA radioligand therapy (RLT) have demonstrated, a reduction of PSA of over 50% leads to statistically significant increase in overall survival. Our clinic’s results show the reproducibility of this data. After 3 sessions of 177Lu-PSMA PSA decreases by an average of 68%. Preserving remissions and increasing quality of life of our patients remain our goals.
Pluvicto® approval by EMA
Following FDA approval in March 2022, European Medicines Agency (EMA) also approved Pluvicto® (lutetium (177Lu) vipivotide tetraxetan) of Novartis in December 2022 for targeted radioligand treatment of progressive PSMA–positive metastatic castration-resistant prostate cancer. The EMA approval is based on the results from the Phase III VISION trial, in which “radioligand therapy with 177Lu-PSMA-617 prolonged radiographic progression-free survival and overall survival when added to standard care in patients with advanced PSMA-positive metastatic castration-resistant prostate cancer”. Pluvicto® is to be used together with androgen deprivation therapy in adults previously treated with androgen receptor pathway inhibitors and taxanes. “The lutetium-177-PSMA was developed by the German Cancer Research Center (DKFZ) in cooperation with Heidelberg University Hospital and Heidelberg University.”
Interview with a patient, September 2022
The patient A.G., 72 y.o., a molecular biologist himself, was diagnosed with metastatic prostate cancer in September 2018. After the conventional standard-of-care treatment (chemo- and antihormonal therapy) there were still residues of the primary tumour in the prostate, and lymph nodes and bone metastases. Up to date he has gone through 9 sessions (3 cycles) of 177Lu-PSMA therapy in the course of three years, initiating a new cycle once a routine control 68Ga-PSMA PET/CT detected PSMA expressing cancer lesions. The therapy has been extremely successful for A.G.: high response and hardly any side effects. Targeted radioligand therapy brings us much closer to the goal of making prostate cancer just another treatable chronic disease, at the same time preserving a decent quality of life, much like e.g. diabetes.
Manufacturing personalized radioligands in the laboratory
FAPi-based targeted theranostics for treating radioiodine-refractory differentiated thyroid cancer
The study of FAPi-based lutetium-177 therapy in the All India Institute Of Medical Sciences in New Delhi was meant to investigate the therapeutic efficacy and safety of 177Lu-DOTAGA.(SA.FAPi)2 in RR-DTC patients. 15 heavily pre-treated (min 2 lines of prior treatment with lenvatinib and/or sorafenib) patients with the disease progression were selected based on FAPi PET/CT. An average of 3 sessions of 2 GBq each was administered in an 8-week interval.
Trial comparing radioligand treatment with 177Lu-PSMA-617 to the chemotherapy using cabazitaxel in treating mCRPC
TheraP, a phase II trial comparing radioligand treatment with 177Lu-PSMA-617 to the chemotherapy using cabazitaxel was finalized with 177Lu-PSMA demonstrating a clear advantage over the chemotherapy.
EAU updates its Prostate Cancer Guidelines
After the conclusion of the Vision trials the urological associations start gradually adjusting their Prostate Cancer guidelines, both in diagnostics and treatment. EAU now strongly recommends:
- PSMA PET/CT (with gallium-68 or fluorine-18) as a more accurate diagnostic method than CT and bone scan for the staging of high-risk prostate cancer (PSA > 20 ng/mL, or GS > 7, or clinically palpable tumour in both lobes (cT2c)), and
- 177Lu-PSMA as a therapy of choice for pre-treated (ADT) mCRPC patients with one or more metastatic lesions, highly expressing PSMA on the diagnostic radiolabelled PSMA PET/CT scan.
Both are available in our institution. Make your appointment now.
Nuclear theranostics: what’s next?
While theranostics has immensely improved overall survival and quality of life of NET and prostate cancer patients and is increasingly becoming mainstream, the science is tirelessly working on the next big thing – pan-cancer theranostics based on fibroblast activation protein (FAP) found in the cancer-associated fibroblasts (CAF). With many widespread cancers in question, this would be truly revolutionary. First-in-human PET/CT studies of 68Ga-FAPI have demonstrated excellent results. A tracer derivative better suited for the therapeutical ends is within reach.
Bone metastases, prostate cancer and theranostics
Bone metastases are a common secondary cancer of many cancer types, such as breast (70%), prostate (85%), lung and kidney cancer (40%), due to the unique bone microenvironment. Tumors mostly metastasize to axial skeleton (i.e. bones of the trunk and pelvis) rather than to appendicular skeleton (limbs and girdles) along the distribution of the red bone marrow.
Gallium-68 has demonstrated superiority to Fluorine-18 in digital PSMA-PET/CT scans for staging prostate cancer
Fluorine-18 is a commonly used isotope utilized for conducting PSMA-PET/CT to stage prostate cancer, due to its longer half-life and higher production capacity as compared to Gallium-68. The latest study, however, has demonstrated superiority of Ga-68, because of the focal unspecific uptake of F-18 in the bones of ribs and pelvis. Without additional follow-up exams or any morphological correlates, this may be misinterpreted as bone metastasis. While nonspecific uptake in other tissues and physiologic uptake in the ganglia can be filtered out, unspecific bone uptake tends to lead to false interpretation and misdiagnosis. Bone metastases do occur in 10% of patients with the newly diagnosed prostate cancer, and 80-90% of patients in the advanced stage. Over-staging the patient may result in inadequate therapy decisions, especially in case of early biochemical recurrence. Read more.
PSMA therapy under more restrictive regimen of 4-week intervals
How oft is the Lu-PSMA treatment conducted? The usual cycle consists of 3 sessions with 6 to 8 weeks interval in-between. Our more restrictive treatment regimen of 3 initial cycles with an interval of only 4 weeks in-between demonstrated >80% response rates even in heavily pre-treated patients. This treatment does not care, “where” the metastases are: lymph nodes, bone, lungs, liver or even tumor in the prostate region itself. The usual “victims” of PSMA ligands, the salivary glands and kidneys, are not significantly affected under this regimen. Read more here.
Check other scientific investigations of our team on the topic.
177Lu-PSMA therapy improves health-related quality of life in patients with mCRPC
On Friday, 17 September 2021, Novartis announced further positive findings from the VISION trial: 177Lu-PSMA-617 therapy delays worsening of physical functioning and the onset of pain symptoms in patients with mCRPC. Hence, beyond extending overall survival and progress-free period, this Breakthrough Therapy also improves health-related quality of life. Read more
National Comprehensive Cancer Network, an alliance of cancer centers in the US, whose guidelines in oncology are applied to treating cancers, has added 68Ga-PSMA-PET imaging to its clinical practice guidelines for prostate cancer. Moreover, it recognized the high precision of this diagnostic tool as a primary stand-alone method and scrapped conventional imaging as a necessary prerequisite for PSMA-PET. Read more in the Urology Times.
Frontiers in Urology
Working group headed by Prof. Markus Hartenbach was able to demonstrate the outstanding diagnostic value of PSMA PET / MRI in biopsy-proven prostate cancer. PSMA-PET/MRI can provide an accurate staging of newly diagnosed prostate cancer. In addition, treatment strategies were changed in almost a third of the patients due to the information of this hybrid imaging technique. The scientific paper was published in the Clinical Cancer Research journal.
The working group headed by Prof. Markus Hartenbach MD was able to demonstrate the superiority of PSMA PET in the diagnosis of biochemical recurrence of prostate cancer, even at low PSA levels. Moreover, this diagnostic tool adds significant information to standard CT/MRI, changing treatment strategies in a significant number of patients. PSMA-positive lesions were detected in 85.5% patients, whereas 57.3% had no suspicious correlates according to the MRI or CT reports. Detection rates were 65% for a PSA value of 0.2 to <0.5 ng/ml, 85.7% for 0.5 to <1, 85.7% for 1 to <2 and 100% for ≥2. PSMA-PET changed therapeutic decisions in 74.6% of the patients (p < 0.001), with 86% of them being considered for metastases-directed therapies. The scientific paper was published in the “European Journal of Nuclear Medicine and Molecular Imaging”.