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.

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.

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.

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-PSMA^HBED-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.

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”^[1]. 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.”^[2]

^[1] https://www.nejm.org/doi/full/10.1056/nejmoa2107322

^[2] https://www.krebsinformationsdienst.de/aktuelles/2022/news059-metastasierter-prostatakrebs-zulassung-pluvicto-lutetium-177-psma-617-europa.php 

We are thrilled and proud to share that our colleague Prof.Dr. Alexander Haug has been awarded The European Awards in Medicine 2022 in the field of nuclear medicine.

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.

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.

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.

https://uroweb.org/guidelines/prostate-cancer/summary-of-changes

Both are available in our institution. Make your appointment now.

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.

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.

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

On 23 March 2021 Novartis announced positive results of the phase III trial with radioligand therapy ¹⁷⁷Lu-PSMA-617 in patients with castrate-resistant metastatic prostate cancer (mCRPC) after taxane chemotherapy and several androgen deprivation therapies (ADT).

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”.

Markus Hartenbach wins Oncology Council's Young Investigator Award of the North American Association of Nuclear Medicine.