Dr George on the Role of Radioligand Therapy in Prostate Cancer Management

“Lutetium Lu 177 vipivotide tetraxetan has shown us is that there is a role for this therapy throughout the disease continuum, from hormone-sensitive disease all the way through chemotherapy-refractory castration-resistant disease.”

Daniel J. George, MD, the Eleanor Easley Distinguished Professor in the School of Medicine, a professor of medicine, a professor in urology, and a professor in surgery in the Department of Medicine at the Duke University School of Medicine; as well as a member of the Duke Cancer Institute, discussed the therapeutic potential of radioligand therapies for patients with prostate cancer and the subsequent evolution of clinical trial goalposts within this treatment paradigm.

The radioligand therapy Lutetium Lu 177 vipivotide tetraxetan (Pluvicto) has had a crucial role in prostate cancer management, spanning from the management of hormone-sensitive disease all the way through to the treatment of chemotherapy-refractory castration-resistant disease, George began. As Lutetium Lu 177 vipivotide tetraxetan moves into earlier and earlier disease settings—a pattern similar to the historical development and deployment of androgen receptor pathway inhibitors—the established goals for clinical success have necessarily changed, he noted. There is now less concern about overall survival (OS) end points when moving into earlier disease settings, largely because the outcomes for these patient populations are influenced by other confounding factors, he explained.

Instead of prioritizing OS or radiographic progression-free survival outcomes, which have historically been the traditional metrics used in registrational trials for patients with early metastatic hormone-sensitive prostate cancer, George expressed greater enthusiasm for the capability of radioligand therapy to achieve minimal residual disease (MRD). Individual patient treatment goals are not always reflected in the historical trial metrics, he said. However, patients often desire to successfully achieve MRD so they can discontinue therapy, he reported.

Moving forward, if radioligand therapies become a standard component across more areas of the prostate cancer treatment paradigm, they may be used in various sequences, according to George. These potential strategies include fist-line combinations, or induction therapy that is followed by either consolidation or maintenance therapy, he continued. Through these integrations, it is possible that radioligand therapies could enable certain patients in the metastatic hormone-sensitive setting to successfully discontinue treatment, he added.

The overarching objective is to identify and employ a specific combination or sequence of therapies that maximizes the number of patients who reach MRD and are ultimately able to cease treatment, George stated. Although achieving a cure remains the ultimate aspiration, a welcome result for patients is even a break from therapy, which helps to restore their overall health and functionality, he concluded.

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Daniel J. George, MD, discusses the potential of radioligand therapies for patients with prostate cancer and the evolution of this treatment paradigm.

March 2025 decision by the FDA to expand the indication

 of lutetium Lu 177 vipivotide tetraxetan (Pluvicto) to include adult patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) who have received an androgen receptor pathway inhibitor (ARPI) for whom a delay of taxane-based chemotherapy is appropriate, key factors such as the nature of disease progression and patient preferences and treatment goals must be carefully weighed to properly identify ideal candidates for this approach, according to Daniel J. George, MD.

The regulatory decision was based on data from the phase 3 PSMAfore trial (NCT04689828), which showed that patients who received the radioligand therapy achieved a significant radiographic progression-free survival compared with those who transitioned to another ARPI (HR, 0.41; 95% CI, 0.29-0.56; 

 < .0001). The expanded indication followed the initial 

 of the agent for the treatment of adult patients with PSMA-positive mCRPC who previously received an ARPI and taxane-based chemotherapy.

®, George, the Eleanor Easley Distinguished Professor in the School of Medicine, Medicine, Medical Oncology, a professor of Medicine, Medicine, Medical Oncology; and a professor in urology at Duke Health in Durham, North Carolina, discussed which patients he considers for treatment with lutetium Lu 177 vipivotide tetraxetan, the future of radioligand therapy in prostate cancer, and other novel treatment approaches being investigated for patients who experience disease progression on an ARPI-based regimen.

What is your approach for treating patients with mCRPC who experience disease progression following an ARPI-based regimen?

: When patients have metastatic hormone-sensitive prostate cancer [(mHSPC) and are receiving] an ARPI, the prognosis can be quite good in some cases, particularly in those with good prostate-specific antigen [PSA] responses. As the disease progresses into castration-resistant metastatic disease on an ARPI, the clock is ticking.

These are patients who need to be aware, even if they feel well and asymptomatic, that their life expectancy is in that 2-to-3-year range, and it’s not indefinite. The changes are going to come quicker; the need to take on potentially more adverse effects with cytotoxic therapy is going to be greater, and [we need] to recognize that the expectations of therapy are going to be more modest in this setting. With all that said, it’s a spectrum. We have patients who have slow PSA rising and minimal metastatic disease burden on ARPI, for whom we’re going to be comfortable doing a clinical trial of an investigational, unproven agent. We’re going to be comfortable using sipuleucel-T [Provenge] and other types of less immediately cytotoxic therapies.

[Many] patients will have more rapidly progressive disease, higher volume disease, and risk of complications and symptoms. For those patients, using cytotoxic therapy, whether that’s taxane-based therapy or a radioligand therapy, [such as] lutetium Lu 177 vipivotide tetraxetan, is the first major treatment decision.

What are some of the factors you consider when deciding to give chemotherapy or deferring it in favor of radioligand therapy to a patient with mCRPC who is eligible for both treatments?

When I’m addressing a patient at that critical juncture of post-ARPI with disease progression, I’m looking at a couple of things. How is that disease progression? Is it clinical? Is it radiographic? Is it PSA only? Is it a combination of all 3? I’m looking at their tumor volume as well, and at whether the patient is a chemotherapy candidate.

In the real world, a lot of ou r patients are just not good chemotherapy candidates. [Even] if they are, it’s going to come at a physical cost. They [are often] frail and [have] other [comorbidities] that are going to clinically worsen from that chemotherapy. These are the factors that I [use to determine] whether they’re good up-front chemotherapy candidates. If they are willing, starting chemotherapy is a good choice because we know that lutetium Lu 177 vipivotide tetraxetan has an [overall] survival [OS] benefit post-chemotherapy.

We also know that [lutetium Lu 177 vipivotide tetraxetan] has a significant benefit prechemotherapy, and for many of our patients who are not chemotherapy candidates. I use chemotherapy fitness as my first judge, and then it’s patient preference. At the end of the day, they get a voice and this a shared decision. A lot of patients want to put chemotherapy off until they really need to do it, and I’m perfectly comfortable with that. Starting with lutetium Lu 177 vipivotide tetraxetan in the majority of patients is absolutely a reasonable course.

What is your approach to PSMA testing when you are considering using lutetium Lu 177 vipivotide tetraxetan?

[To me, when a patient] has emerging castrate resistance in their disease, that’s the best time to get a PSMA-PET scan. First, it’s our best staging. It’s our most sensitive test for assessing the full extent of the disease, and it gives me peace of mind that there isn’t visceral disease hiding in there. If it is lymph node–only disease, I can feel confident there isn’t [disease] in the bone. Importantly, if there’s oligometastatic disease, if these patients have 1 or 2 areas that are growing but really the rest of the disease is still ARPI responsive, I’ll consider some of these are patients for tumor-directed radiotherapies.

It’s also a theranostic for lutetium Lu 177 vipivotide tetraxetan and I use it as such. It’s important also to be able to gauge at this point in time how ubiquitous and intense that PSMA uptake is. I’m also talking with my nuclear medicine physicians about the scan and their interpretation.

Where do you see the story of radioligand therapy going next within the prostate cancer treatment paradigm?

Lutetium Lu 177 vipivotide tetraxetan has shown us is that there is a role for this therapy throughout the disease continuum, from hormone-sensitive disease all the way through chemotherapy-refractory castration-resistant disease. Not unlike how ARPIs were developed, the goalposts have changed as we move into these other disease spaces.

I’m less worried about being able to see the OS end points as we move earlier and earlier [into new disease settings], because there are so many other things that affect the outcomes in these patients. I’m more interested in the ability to get to minimal residual disease [MRD]. If we think about what our goals are for patients with early mHSPC, historically we’ve [designed] the registrational trials to look at rPFS and OS, but if you talk about our patients, those aren’t necessarily their goals. They want to get to MRD and to get off therapy.

In the future, if radioligand therapies are part of the mix of treatments, whether they be up-front combinations or induction followed by consolidation or maintenance therapy, they may allow us to get patients off treatment—maybe not all patients, but some patients in the metastatic, hormone-sensitive setting. That’s going to be an important aspect of this.

Our goal as patient advocates is ultimately to come up with a combination or sequence of therapies that get us to MRD in the greatest number of patients and ultimately get patients off treatment. If that’s a cure, that’s wonderful, but even a break from therapy for these patients is welcome in order to restore some of their functionality and overall health.

Are there any novel agents being developed for patients with mCRPC that are of particular interest to you?

It’s probably one of the most exciting times in prostate cancer drug development right now. We have more mechanisms to target now than ever before, and what started out as just basically the AR pathway has now expanded to PSMA-targeted approaches—not just radioligands, but potentially antibody-drug conjugates and bispecific antibodies.

Beyond PSMA, we’re seeing evidence for [targeting] 

 [alterations]. We’re getting more targets in prostate cancer, and we’re getting mechanisms to start targeting. Other targets that are drivers of more aggressive forms of prostate cancer, and more androgen-independent forms of prostate cancer are coming into clinic. This is an incredibly important aspect, because before we were limited to what we could target in prostate cancer. We’d get these next-generation sequences and our big list of mutations, and things would be non-actionable.

You’re going to see now more and more actionable targets in that profiling is going to become more and more critical in how we’re treat these patients. That’s going to make the testing and diagnostics all the more important. And I hope you know that today, we can already justify doing that on a systematic level for everybody with advanced prostate cancer, knowing that these therapies are coming.

FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed November 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication

FDA approves Pluvicto for metastatic castration-resistant prostate cancer. FDA. March 23, 2022. Accessed November 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pluvicto-metastatic-castration-resistant-prostate-cancer?utm_medium=email&utm_source=govdelivery

Articles

Daniel J. George, MD, discusses the role of lutetium Lu 177 vipivotide tetraxetan in metastatic CRPC and patient selection considerations.

Lutetium Lu 177 Vipivotide Tetraxetan Enables Some Patients with mCRPC to Avoid Chemotherapy

Staying abreast of ongoing research in the prostate cancer landscape is essential to continue identifying potentially better biomarkers as targets, particularly for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic hormone-resistant prostate cancer (mHRPC), according to Scott T. Tagawa, MD, MS, FACP, FASCO.

Of note, topline data from the phase 3 PSMAddition trial (NCT04720157) revealed that the study met its primary end point, demonstrating statistically significant and clinically meaningful benefit in radiographic progression-free survival, along with a positive trend in overall survival, in patients with PSMA-positive, metastatic hormone-sensitive prostate cancer (mHSPC) treated with lutetium Lu 177 vipivotide tetraxetan (Pluvicto) plus standard of care (SOC), comprising androgen receptor pathway inhibitor (ARPI) therapy and androgen deprivation therapy (ADT), vs those given SOC therapy alone.

Furthermore, the role of lutetium Lu 177 vipivotide tetraxetan has continued to shape the PSMA-positive mHRPC treatment paradigm, especially 

following the FDA’s expanded indication

 of the agent to include patients previously treated with ARPI therapy who are eligible to delay taxane-based chemotherapy.

“It's not shocking to me and most people that prior chemotherapy exposure is not required for [lutetium Lu 177 vipivotide tetraxetan],” Tagawa said in an interview with 

® during Prostate Cancer Awareness Month, observed annually in September. “It's just the way the trials were done and the way the FDA approves [treatments]. It's nice to have [both indications] as options.”

In the interview, Tagawa highlighted the importance of continued research in the prostate cancer landscape, current screening tests, and sequencing strategies following ARPI therapies.

Tagawa is a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center in New York.

Given the incidence of prostate cancer within the general population in the United States and around the world, what is the importance of continued research in this landscape to improve outcomes for patients?

: As the most common noncutaneous malignancy, at least in the Western world, is it important [to continue raising awareness of prostate cancer], especially for the ends of the spectrum. There’s a big population [where patients have prostate cancer] discovered by screening who might have low- or very low–risk disease that is probably best served for active surveillance. [It would be great] if there was a biomarker where we can know for sure that [a low-risk malignancy] is not something that is going to affect the patient's lifetime, using more noninvasive ways to discover that.

Although the vast majority of patients who are diagnosed with prostate cancer never die of prostate cancer, depending on the year, it still is one of the leading causes of death due to cancer among people born with prostates. We also [want to drive further research] because we want to be able to cure those who [currently] might not be considered curable, or to at least extend life so that more people die with, rather than of, prostate cancer, as well as to improve the quality of life [QOL]. Something that could [help] maintain QOL and improve QOL would be a great win.

What are the current screening tests used to diagnose prostate cancer?

The most common screening test we have for prostate cancer is a blood test [to measure the amount of] prostate-specific antigen [(PSA) in the blood], and it's really a good test. It needs to be interpreted in the right way, and this is more in the primary care realm. When used in the right way, a simple PSA [test] can be quite powerful.

There are additional screening tests available, both as imaging and [with] blood and urine. We're no longer in an era where it's ‘wrong to screen.’ We want to have shared decision-making about screening. Even something as mundane as PSA, when interpreted in the right context, which includes age and prostate size, can be quite powerful.

Within the mHRPC and mHSPC spaces, ARPIs have altered the treatment paradigm. Beyond this, when patients progress and require subsequent therapy, what are some of the challenges and considerations for treatment in this setting?

Clearly, ADT and ARPIs work incredibly well, and we hope to improve upon them. However, they're generally not curative, unless they're combined with radiation or [another therapy]. A big unmet need is to improve upon their initial use and have options post-ARPI, where traditionally there was chemotherapy and occasional subsets that were not chemotherapy. Chemotherapy is great in that it works for many patients and can improve QOL, but many patients don't want to [receive] chemotherapy, and we're not too happy giving chemotherapy some of the time.

[Now, we] have [more treatment] options than we did 5 years ago and 10 years ago when we had some options, because we didn't have anything 15 years ago. Arguably, all [treatments beyond ARPIs] are what we call biomarker-selected. There are certainly clinical biomarkers that [can indicate] a person needs chemotherapy. Genomics [are used] in terms of PARP inhibitors. Imaging [is used] in terms of either of the targeted radionuclides, radium-223 [Xofigo] in terms of bone scans, and then lutetium Lu 177 vipivotide tetraxetan and others that are coming similar to that with PSMA PET. 

All of those non-chemotherapies are somewhat [biomarker] selected, and there are certainly promising drugs that are for selected patient populations or for all comers in the AR pathway that will work beyond the traditional ARPI.

Overall, how have radioligand therapies, like lutetium Lu 177 vipivotide tetraxetan, affected those later-line settings for prostate cancer?

We have a bone-targeted [agent with radium-223], and we have the PSMA-targeted [radionuclide therapy with lutetium Lu 177 vipivotide tetrax]. One of the nice things about both of them, and specifically for the PSMA target, is that it's another target beyond the AR pathway and microtubules, with a different mechanism of action. Although most patients will develop resistance to AR-targeted therapies, AR and PSMA remain, so it's a good target for the majority [of patients]. Most tumors have some raised sensitivity, so we can selectively deliver radiation to those PSMA-positive tumors, and we would expect there to be improvements in outcome, and we have [seen these improvements]. Overall survival in one study, a radiographic progressive model in another study, and QOL improvements for both; therefore, it's nice to have that as an option.

What are the factors to be aware of when determining whether docetaxel is better first before selecting radioligand therapy, or vice versa?

My bias is the target, PSMA. If PSMA is not [expressed] very much, then it doesn't mean that a PSMA-targeted agent can't work, but it's been shown that the PSMA PETs are a very good biomarker, specifically for PSMA small molecules, particularly with [lutetium Lu 177 vipivotide tetraxetan].

[The lack of PSMA expression would represent] deselection from PSMA targeting, or for [treatment with] something else, like chemotherapy. In certain organs, we worry about liver metastases, which are negatively prognostic, no matter what [treatment you select], including chemotherapy. However, we know that data are coming from my former fellow, Himisha Beltran, MD, [of Dana-Farber Cancer Insitute], that [suggest that] even when PSMA is positive in certain organs, like the liver, it tends to be a little bit less [compared with the primary tumor]. The biases in those types of situations might [cause you to lean] more toward chemotherapy; some tumors, however, can have very homogeneously high levels of PSMA. It doesn't mean that something in the liver can't respond [with heterogeneous levels of PSMA].

There may be certain characteristics [we can consider]. We can administer these small molecules to someone with renal failure; if they're on dialysis, we have to make sure [they’re appropriate candidates for lutetium Lu 177 vipivotide tetraxetan], where there's more data with chemotherapy [in this population]. There are other individual factors, such as someone who's worried about their family [while receiving radioligand therapy]. We've never seen a family member truly have exposure to radiation that has led to a problem, but it is a risk, whereas chemotherapy doesn't have that risk.

Then, [radioligand therapy is] not fully available [everywhere]. There are many more places today [offering lutetium Lu 177 vipivotide tetraxetan] than there were 6 months ago and years ago, but chemotherapy is available pretty much everywhere, whereas some people have to travel for drugs like lutetium Lu 177 vipivotide tetraxetan.

Are there any other novel classes of drugs that you’re keeping your eye on that have the potential to be used in clinical practice?

I'd say a minor improvement in terms of incremental progress for the field, but [something that] is a major improvement for some patients, is with similar drugs coming in the same space, meaning there are choices. Some of those are very practical choices, [such as,] how many treatments and how often? [Adjusted treatment schedules can be] patient-friendly if they [are shown to] work.

We know that [data from the] PSMAddition trial are positive, as shown in a press release. We don't know how positive yet; however, it would be nice [to have this option in the mHSPC space].

[Beyond] lutetium Lu 177 vipivotide tetraxetan, what about other things? I'd say the bigger incremental move is from beta to alpha [radioligand therapies]. The linear energy transfer is higher with more potency, which is something that is a little bit more than incremental.

A major improvement would be [to expand] beyond PSMA. Other targets are of interest, with some of them overlapping with this AR-positive group, but it's OK to have overlapping things because it's not exactly the same.

A huge unmet need, whether we're talking about something radioactive or nonradioactive, but for those patients who are AR-low, there are other targets. Using the same type of approach, whether it's with lutetium Lu 177 vipivotide tetraxetan or something else, might work in that other patient population. [Other targets could include] DLL3, CEACAM5, or others.

My bias is in the world of theranostics, meaning dual picture, where in vivo, we look at all the tumors to see what is there. That's a great way to select an agent, whether it's a chemotherapy-type agent that's targeted, an immune-type agent, or something that's radioactive. That is something we should incorporate more. Even docetaxel has some emerging biomarkers that help us decide whether it should be AR only or combined with chemotherapy. Should we add docetaxel? That is also a major improvement, even though docetaxel is one of our oldest drugs. If we can figure out how to improve the therapeutic index, then more patients will benefit more so that the efficacy vs the adverse effects is much more in favor of the patient.

Considering it is Prostate Cancer Awareness Month, what is your main takeaway message for colleagues regarding the current state of treatment and future implications of treatment?

There has been, traditionally, both on the patient side and on the physician side, a little bit of nihilism in terms of prostate cancer. There are a lot more options we have today, and many different categories of options that have improved both quantity and QOL. [Even for older patients], everything should be discussed. If someone says no, with informed consent, that's fine. It doesn't matter if they're 50 or 90 years of age; however, we should offer these [options].

It's not just the treatment; it is the testing for treatments, such as assessing the tumor genome or germline alterations, and remembering that sometimes germline [results] are as important or even more important for their grandchild. We want to approach every single patient with prostate cancer with an open mind and open eyes and discuss everything. Not that everyone must have every single drug, but they should at least have all the testing and therapeutics on the table.

Novartis Pluvicto demonstrates statistically significant and clinically meaningful rPFS benefit in patients with PSMA-positive metastatic hormone-sensitive prostate cancer. News release. Novartis. June 2, 2025. Accessed September 18, 2025. https://www.novartis.com/news/media-releases/novartis-pluvictotm-demonstrates-statistically-significant-and-clinically-meaningful-rpfs-benefit-patients-psma-positive-metastatic-hormone-sensitive-prostate-cancer

FDA expands Pluvicto’s metastatic castration-resistant prostate cancer indication. FDA. March 28, 2025. Accessed September 18, 2025. FDA. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-expands-pluvictos-metastatic-castration-resistant-prostate-cancer-indication

Scott T. Tagawa, MD, MS, FACP, FASCO, discusses the evolving role of radioligand therapies for the treatment of PSMA-positive prostate cancer.

Radioligand Therapy Sequencing, Novel Targets Continue to Shape Prostate Cancer Care and Research

Scott T. Tagawa, MD, MS, FACP, FASCO, details factors to consider when to use or defer docetaxel after lutetium Lu 177 vipivotide tetraxetan in mCRPC.

Dr Tagawa on Factors for Lutetium Lu 177 Vipivotide Tetraxetan Use Before Docetaxel in mCRPC

“My bias is the target, PSMA; therefore, if PSMA is not there very much, then it doesn't mean that a PSMA-targeted agent can't work, but it's been shown that the PSMA PETs are a very good biomarker, specifically for PSMA small molecule, particularly with lutetium Lu 177 vipivotide tetraxetan.”

Scott T. Tagawa, MD, MS, FACP, FASCO, a professor of medicine and urology at Weill Cornell Medicine and an attending physician at NewYork-Presbyterian – Weill Cornell Medical Center, discussed factors to consider when selecting between lutetium Lu 177 vipivotide tetraxetan (Pluvicto) and docetaxel for the treatment of patients with prostate-specific membrane antigen (PSMA)–positive metastatic castration-resistant prostate cancer (mCRPC) after prior treatment with an androgen receptor pathway inhibitor (ARPI).

FDA expanded the indication for lutetium Lu 177 vipivotide tetraxetan

 to include patients with PSMA-positive mCRPC who received prior ARPI therapy who are also eligible to delay taxane-based chemotherapy. When 

the radioligand therapy was initially approved

 in March 2022, it was indicated for patients with PSMA-positive mCRPC who have previously received other anticancer therapies, such as an ARPI and taxane-based chemotherapy.

When considering lutetium Lu 177 vipivotide tetraxetan as a potential treatment, PSMA remains the key factor, Tagawa explained. If PSMA is not present, a PSMA-targeted agent could still be effective, Tagawa continued, but he noted that PSMA PET scans serve as a useful biomarker for PSMA, particularly for a PSMA small molecule like lutetium Lu 177 vipivotide tetraxetan.

Furthermore, metastases in the liver are an aspect of concern, particularly because they are a poor prognostic marker, irrespective of treatment selection, Tagawa continued. He noted that data have suggested that even when there is PSMA-positivity in select organs, such as the liver, it can be expressed at lower levels than the primary tumors; in these cases, using chemotherapy may be a better option than deferring it, he stated. Some tumors and metastases could also have homogenously high levels of PSMA, and even in cases of lower PSMA expression, metastases may still respond to treatment with radioligand therapy, he added. Nevertheless, in these scenarios, tailoring treatment based on patient characteristics matters, he asserted. For example, small molecules could be administered to patients with renal failure, although if they are receiving dialysis, focusing on the data regarding chemotherapy use is important, Tagawa contextualized. Other individual factors, such as treatment preference, matter when selecting between radiation and chemotherapy, he added.

Moreover, radioligand therapy is not as widely available as chemotherapy. However, that has changed within the past year, Tagawa emphasized. This factor could also influence when and if patients receive docetaxel with lutetium Lu 177 vipivotide tetraxetan, especially if traveling to a clinic could pose as an obstacle for patients, he concluded.

Experts discuss the evolving role of radioligand therapy during Prostate Cancer Awareness Month.

Prostate Cancer Awareness Month: The Evolving Role of Radioligand Therapy | Supplements and Featured Publications

Dr George on the Role of Radioligand Therapy in Prostate Cancer Management

Lutetium Lu 177 Vipivotide Tetraxetan Enables Some Patients with mCRPC to Avoid Chemotherapy

Radioligand Therapy Sequencing, Novel Targets Continue to Shape Prostate Cancer Care and Research

Dr Tagawa on Factors for Lutetium Lu 177 Vipivotide Tetraxetan Use Before Docetaxel in mCRPC