Reference: 2026 | Issue 7 | Vol 12 | Page 42
National MDT for complex cases of testicular cancer
St Vincent’s University Hospital has launched a new initiative which aims to improve access to appropriate treatment and optimal outcomes for patients with testicular cancer (TC). On foot of the hospital being designated as a National Centre for Retroperitoneal Lymph Node Dissection for Testicular Cancer, a national multidisciplinary team (MDT) has been established to specifically discuss and manage complex cases of TC.
Speaking about the initiative at the 2026 John Fitzpatrick Genitourinary Cancer Conference, Prof Ray McDermott, who leads the project, said the monthly meeting is drawing more and more cases.
“We’ve had some great buy-in. We’ve had three meetings so far. They are happening once a month at the moment, on the first Tuesday of the month. The first meeting was kind of a trial run, and we discussed a handful of patients. At the second meeting, we discussed 10 patients from all around the country. At the third meeting, we discussed 12 patients,” he said.
The meeting takes place by Zoom and clinicians from around the country can submit cases for review and discussion. Chosen cases are reviewed by the MDT, which includes urology and andrology surgeons, medical oncologists with special interests in urological and testicular cancer, pathologists and radiologists with a special interest in urological cancer, urology and medical oncology fellows, specialist advanced nurse practitioners and clinical nurse specialists, as well as a dedicated MDT coordinator and data manager.
“There are 170 testicular cancers in Ireland every year. I don’t think we need to discuss all of them, but we need to discuss a good portion of them, probably a bit more than we’re discussing at the moment. And I think we need standardised protocols for each and every one of those patients. That’s all part of what we would hope to achieve over the next few years,” Prof McDermott said.
Lu-PSMA in the real-world setting
Last year the HSE took the decision not to approve reimbursement for lutetium-PSMA-617 (Lu-PSMA-617) for the treatment of progressive prostate-specific membrane (PSMA)-antigen positive metastatic castration-resistant prostate cancer (mCRPC). The decision followed the HSE Drugs Group’s conclusion that the therapy did not represent optimal use of limited HSE resources. The announcement was met with widespread criticism from the Irish oncology community, but a presentation at the recent John Fitzpatrick Genitourinary Conference showed the organisational complexity involved in delivering this therapy in a real-world setting.
Lu-PSMA-617 was approved for reimbursement in Canada in December 2024, allowing the treatment to be provided at selected cancer centres, including Princess Margaret Hospital in Toronto. Dr Di Maria Jiang, Medical Oncologist at Princess Margaret’s, said providing the treatment has required considerable financial and human resource investment.
“There is a lot of operational complexity in giving this treatment to a heavily pretreated patient population. There are a lot of resources and admin support that we need to bring this to our patients,” Dr Jiang said.
“There is a lot of work in the background trying to figure out the right patient population. We have to get CT scans, we have to get PSMA PET scans, and a lot of the time when we get PSMA PET scans, and then our radiologist has to determine whether they meet the VISION [trial] criteria. So, from the time that you have a patient with PSA rise and they are potentially eligible for Lu-PSMA, you have to get the CTs, then you have to get the PSMA PET, then you have to do the tumour board meeting, and then you have to order the drug, which takes about a couple of weeks. That process takes time and a lot of resources.”
The approval of Lu-PSMA was based on the open-label, phase 3 VISION trial, which evaluated 177Lu-PSMA-617 in patients with mCRPC previously treated with at least one androgen-receptor–pathway inhibitor (ARPI) and one or two taxane regimens and who had PSMA-positive gallium-68 (68Ga)-labeled PSMA-11 PET CT scans.
Patients were randomly assigned to receive either 177Lu-PSMA-617 (7.4 GBq every six weeks for four to six cycles) plus protocol-permitted standard care or standard care alone. Protocol-permitted standard care excluded chemotherapy, immunotherapy, radium-223 (223Ra), and investigational drugs. Lu-PSMA was associated with prolonged imaging-based progression-free survival (PFS) and overall survival (OS) when added to standard care.
Princess Margaret Hospital treated its first patient with Lu-PSMA in January 2025. As of April 2026, 75 patients had been treated.
“In terms of who we give Lu-PSMA to, the patient selection criteria are really not standardised across institutions but, generally speaking, we first look at their prior therapies. Do they meet the [VISION trial] criteria? They have to have previous ARPI and prior taxane chemotherapy. Sometimes we see patients with bone-only disease on PSMA PET, and we actually still recommend radium-223 in that case,” Dr Jiang explained.
“If we have a patient with BRCA, and they have not had a PARP inhibitor, we’ll usually go for that before they get Lu-PSMA. And then generally speaking, they have to have reasonable blood counts. At our institution, that is usually haemoglobin above 80 and platelets above 75, otherwise it really becomes a problem.”
Patients are required to comply with radiation safety protocols as they are radioactive following treatment and, therefore, must avoid public transport etc. This can become an issue if patients have to be admitted to hospital.
The Princess Margaret Lu-PSMA experience has uncovered important differences between the clinical trial and the real-world setting.
“As expected, compared to the VISION trial, in the real-world setting, we are seeing patients who have potentially more aggressive disease, with more de novo metastasis, more liver metastasis. We see patients with higher baseline PSA coming in. We see patients with more anaemia. We see a lot more patients who are just post-docetaxel because patients do not usually want to go through another line of chemotherapy if Lu-PSMA is available,” Dr Jiang said.
“In terms of our response rate so far, PSA50 response rate is 38 per cent compared to 46 per cent in VISION. It is a little bit less, but otherwise, in terms of tolerability, the real-world experience has actually been quite similar. We do see a little bit more kidney dysfunction, but so far, there hasn’t been any treatment discontinuation due to adverse events. All of our patients have stopped treatment due to progressive disease.”
“Overall, it is a bit of a steep learning curve to bring this drug into clinical practice but I think, with multidisciplinary effort and experience, it can be done,” Dr Jiang concluded.
Evolving landscape for BCG-naïve NMIBC
The treatment of BCG-naïve and unresponsive non-muscle-invasive bladder cancer (NMIBC) is set for significant change, according to Dr Max Kates, Director of the Division of Urologic Oncology, Johns Hopkins Memorial Hospital, US. Speaking at the 2026 John Fitzpatrick Irish Genitourinary Cancer Conference, Dr Kates predicted a change in practice as a result of important clinical trial data published in the last year.
He pointed out that a number of drugs have been approved in the US in recent years for this patient population, with pembrolizumab receiving FDA approval in 2019, followed by approval for adstiladrin in 2022, nogapendekin-alfa-inbakicept-pmln (NAI) in 2024, and TAR-200 (Inlexzo) in 2025. Several other potential therapies are in development including EV-70, TARA-002, Fidia, Oncofid, and NonoDoce.
Based on these approvals and newly-published trial data, treatment strategies for NMIBC are evolving. In the past, the strategy was to treat with BCG, then move on to a second-line therapy or enter a clinical trial, before ultimately progressing to radical cystectomy. Today, patients are likely to receive several lines of therapy before reaching the clinical trial point.
“Our evolving strategy is quite confusing and quite problematic,” Dr Kates said. “Patients undergo BCG, then they may go on to a second-line therapy, maybe a third-line therapy, and who knows, maybe a fourth-line therapy, depending on the approval pathways, and then radical cystectomy. But that’s a very dangerous strategy. We’re giving our patients more bladder toxicity and more financial toxicity to the healthcare system, with really unclear long-term benefits.”
Several recent trials have focused on this issue. In his presentation, Dr Kates highlighted three phase 3 randomised, open-label trials in particular – ALBAN, POTOMAC, and CREST.
POTOMAC evaluated whether the addition of durvalumab to BCG induction and maintenance therapy improved outcomes versus BCG induction and maintenance alone. At median follow-up of 60.7 months, there was a 32 per cent reduction in the risk of recurrence of high-risk disease or death by any cause for durvalumab plus BCG versus BCG alone (HR 0.68; 95% CI 0.50-0.93; log-rank P = 0.0154), and 24-month disease free survival rates were 86.5 per cent (95% CI 82.2-89.8) and 81.6 per cent, respectively.
The three-arm CREST trial evaluated subcutaneous sasanlimab in combination with BCG versus BCG monotherapy in patients with high risk NMIBC (HR-NMIBC). At a median follow-up of 36.3 months, the rate of recurrence of high-grade disease was reduced by more than 50 per cent with sasanlimab plus BCG induction and maintenance compared to BCG induction and maintenance alone.
However, not all findings have been positive. The ALBAN trial looked at intravenous atezolizumab and intravesical BCG versus BCG alone in BCG-naïve HR-NMIBC. At a median follow-up of 35.3 months, there was no statistically significant difference in event free survival between the arms (HR 0.98; 95% CI 0.71-1.36; P=0.9106).
In all three trials, the addition of immune checkpoint inhibitors (ICIs) to BCG significantly increased grade ≥3 treatment-related adverse events compared to BCG alone, ranging from 20 per cent to over 40 per cent in combination arms. Common toxicities included urinary frequency, haematuria, and immune-related adverse events like fatigue and rash.
Despite differences in methodology and protocols, all three trials were similar in the finding that one out of 10 patients recur at the three-month time point. It took another two years for another one of 10 patients to recur. Dr Kates said this shows that “disease persistence is perhaps our biggest problem”.
“All these trials showed us that basically, if you have recurrences over a three-year period, half of them will be at the three-month time point. It will take the other half three years to show up.”
“The evolving strategy of multiple lines of therapy is quite simply not going to work in this disease space,” he said. “Relying on second-line therapies is a difficult task, extraordinarily expensive, and impacts a fraction of total NMIBC patients. Second-line is already behind the eight ball. Marginal gains to BCG-naïve NMIBC will impact many patients, but we really need to do it safely without increasing toxicity.”
“Maximising long-term cancer control for NMIBC patients starts with improved treatment strategies for BCG-naïve NMIBC, rather than relying on second- and third-line therapies as salvage treatments,” Dr Kates said.
“The future paradigm is really going be a personalised approach based on biomarkers and other factors, in which we have multiple options up front and don’t rely so heavily on salvage lines of therapy,” he said.
“The biggest thing I’ve learned from these trials is that we have a problem with our three-month recurrence rates, and we need to understand how to improve outcomes for this group of patients.”
Changes to testicular tumour classification imminent
The next edition of the World Health Organisation (WHO) Blue Book will see important changes to the classification of testicular germ cell tumours (GCTs), according to Prof Dan Berney, Consultant Pathologist at Barts Health NHS Trust, who is co-editor of the upcoming WHO Classification of Urinary and Male Genital Tumours.
Prof Berney told the conference that the next edition of the WHO series on the classification of human tumours (also known as the WHO Blue Book) will include a new classification system for tumours with somatic transformation. The classification of ‘teratoma with somatic malignancy’ will be replaced by ‘GCT with somatic changes’. This follows the publication of studies which have shown that somatic transformation does not just occur in teratomas.
The reason for this is to ensure that patients with these tumours remain under the care of genitourinary (GU) oncologists and receive appropriate treatment.
“GCTs with somatic transformation are different from GCTs, but they bear more relation to GCTs than they do to their somatic counterparts. It is important that they are not hived off into the sarcoma community. So, if you have a rhabdomyosarcoma-like transformation, these tumours should stay under the care of a GU oncologist because there is still a chance that they will be responsive to GU-type therapy, and that is probably the best way to go,” Prof Berney said.
In the new classification system, somatic type rhabdomyosarcoma will be referred to as sarcoma-like rumour of germ cell origin (rhabdomyeloblastic phenotype). Somatic type unclassified sarcoma will be referred to as the undifferentiated phenotype, and embryonic-type neuroectodermal tumours will change to embryonic-type neuroductal tumour of germ cell origin, while somatic-type enteric adenocarcinoma and squamous cell carcinoma will be referred to as enteric and squamous phenotypes. Somatic-type leukaemia/lymphomas will, in future, be called leukaemia/lymphoma-like tumour of germ cell origin. Tumours with a combination of conventional and somatic-type will be defined according to ‘components’, ie, proportion of yolk sac, seminoma, rhabdomyoblastic phenotype etc.
He pointed out that characteristic features of GCT with somatic malignancy include widespread aneuploidy, distinct epigenetic signatures, mutations that are otherwise rare in testicular GCTs. He added that identification of somatic malignancy component could be more important than their precise histological subclassification.
The forthcoming edition of the Blue Book will also include new prognostic factors for recurrence in patients with clinical stage 1 seminoma and non-seminoma. Prof Berney said this change is important for the 20-30 per cent of patients for whom orchidectomy does not deliver cure.
After many years of debate, the new edition will include invasion of the soft tissues, particularly with the hilum, as an important prognostic factor in stage 1 seminomas.
This significant change follows the publication of a Danish study of patients with stage 1 seminoma, which was published in the Journal of Clinical Oncology in 2024.
The multivariable analysis showed that while rete testis invasion is associated with a hazard ratio (HR) of 1.81 (95% CI 1.19-2.75; P=0.0058), rete testis invasion with hilar soft tissue invasion delivers a HR of 2.83 (95% CI 1.82-4.38; P<0.0001).
“Rete invasion and hilar soft tissue invasion are really strong predictors of relapse and are very important to mention in every testicular [pathology] report,” Prof Berney said.
The presence of lymphovascular invasion (LVI) was shown to confer a HR of 1.82 (95% CI 1.22-2.70; P=0.0032), while HRs for elevated β-hCG and LDH were 1.89 (95% CI 1.35-2.64; P=0.002) and 1.67 (95% CI 1.19-2.34; P=0.0031). The study concluded that patients with all four of these risk factors had a 62 per cent chance of recurrence compared to 6 per cent in patients with none of these factors.
In stage 1 non-seminomas, hilar soft tissue invasion is also a risk factor for recurrence (HR 1.70; 95% CI 1.17-2.48; P=0.0056), as is the presence of LVI (HR 3.48; 95% CI 2.38-5.10; P<0.0001). Other risk factors to be included in the list are tumour size and embryonic carcinoma predominance.
Addressing cardiovascular risk in testicular cancer survivors
As survival rates for testicular cancer (TC) improve, new challenges have emerged. Platinum-based chemotherapy is associated with a seven-fold increased risk of cardiovascular disease, and approximately one in five TC survivors develops metabolic syndrome, which significantly contributes to long-term mortality.
Recognising this growing issue, Memorial Sloan Kettering (MSK) Cancer Center in New York City decided to take action.
“Today, most men with TC, even those with advanced disease, are cured. But with that success comes a new challenge. Many survivors go on to develop metabolic syndrome, impacting not just lifespan, but health span. And yet, metabolic screening is not consistently integrated into routine oncology care,” said Ms Maryann Carousso, a nurse practitioner at MSK’s Sidney Kimmel Centre for Prostate and Urologic Cancers.
“At MSK, approximately 50 to 60 men receive outpatient chemotherapy each year, creating an opportunity to integrate structured metabolic screening into routine care. The clinical problem at MSK was a lack of a standardised process for metabolic syndrome screening, resulting in missed opportunities for early risk identification and intervention.”
The hospital introduced a structured, standardised metabolic screening process which was aligned with the patient’s chemotherapy regimen. Patients undergo baseline screening on day one of the first chemotherapy cycle. Metabolic measures are recorded, including anthropometrics with waist circumference, fasting metabolic laboratory results, and morning testosterone. Patients are then followed at regular intervals after treatment, with management guided by risk level, ie, the number of metabolic syndrome criteria met.
“For patients at low risk, defined as zero to one criterion, management focuses on lifestyle modification including weight management, regular physical activity, and a heart healthy Mediterranean style diet with annual re-screening. For those at moderate risk with two criteria, lifestyle interventions are intensified and targeted referrals are considered. This may include nutritional support, primary care or cardiology for hypertension or dyslipidaemia, endocrinology for elevated glucose, and men’s sexual health for low testosterone. Re-screening is recommended within six to 12 months. Patients with three or more criteria meet the definition of metabolic syndrome and require more intensive management. This includes treatment of identified risk factors, consideration of pharmacologic therapy, and closer follow-up typically at six months,” Ms Carousso explained.
“To date, 31 patients have been screened. Most were low risk, but about 16 per cent were identified as moderate to high risk, which really highlights the value of early screening. Importantly, several of these patients required initiation of antihypertensive and or lipid-lowering therapy, showing that this approach can directly inform targeted interventions,” she said.
Ms Carousso concluded by saying: “Our experience demonstrates that metabolic screening is feasible within routine oncology care and supports early risk-based intervention. Importantly, this approach is scalable and has the potential to be applied more broadly across oncology populations. As survivorship continues to improve, integrating metabolic screening is a critical step toward optimising long-term health, not just cure.”
