Delayed cytoreductive nephrectomy in adults with metastatic renal cell carcinoma and vena cava tumor thrombus treated with immunotherapy-based neoadjuvant therapy: A systematic review

Abstract

Introduction

Renal cell carcinoma (RCC) invades the inferior vena cava (IVC) in 4%–10% of cases, increasing the risk of surgical complications that affect oncological outcomes.

Materials and methods

The research question was defined using the PICOST acronym. An exhaustive search, material selection, and data extraction were conducted in duplicate and independently. Original articles were included on patients with metastatic RCC (mRCC) with thrombus in the IVC, treated with immune checkpoint inhibitors with or without tyrosine kinase inhibitors (TKIs) and cytoreductive nephrectomy (CN). Studies involving patients with thrombi localized solely to the renal artery or atrium were excluded.

Results

A total of 17 articles were included: one retrospective cohort, five retrospective case series, and 11 retrospective case reports. In total, 32 patients were analyzed; 10 were excluded due to the absence of metastases. In most cases, the size of the primary tumor decreased. Regarding the thrombus in the IVC, based on the level, out of 22 patients, 7 remained unchanged, 13 showed a reduction (9 by one level, 3 by two levels, and 1 by three levels), and one showed an increase. In another case, the magnitude of the reduction in thrombus size or level was not specified. Tumor thrombus size decreased even in cases where the level remained unchanged.

Conclusions

Patients with mRCC and thrombus in the IVC may benefit from neoadjuvant treatment with immune checkpoint inhibitors, with or without TKIs, and delayed cytoreductive nephrectomy.

Resumen

Introduccción

El carcinoma de células renales (CCR) invade la vena cava inferior (VCI) en 4% al 10% de los casos, lo que incrementa el riesgo de complicaciones quirúrgicas que afecta los resultados oncológicos.

Material y métodos

La pregunta de investigación se definió utilizando el acrónimo PICOST. La búsqueda exhaustiva, la selección del material y la extracción de datos se realizaron de forma duplicada e independiente. Se incluyeron artículos originales sobre pacientes con CCR metastásico (CCRm) con trombo en VCI, tratados con inhibidores de puntos de control inmunológico, con o sin inhibidores de Tirosina Cinasa (TKI) y nefrectomía citorreductora (NC). Se excluyeron estudios con pacientes con trombos solo en arteria renal o aurícula.

Resultados

Se incluyeron 17 artículos. Una cohorte retrospectiva, 5 series retrospectivas de casos y 11 reportes retrospectivos de casos. En total 32 pacientes, se excluyeron 10, por ausencia de metástasis. En la mayoría de los casos, disminuyó el tamaño del tumor primario. Respecto al TT en VCI, en cuanto al nivel, de los 22 pacientes, 7 se mantuvieron sin cambio, en trece bajó (en 9 un nivel, en 3 dos niveles, en 1 tres niveles) en uno se incrementó. En otro, no se especificó magnitud de la disminución del tamaño ni del nivel del trombo. El tamaño del trombo tumoral disminuyó inclusive en los que no cambiaron de nivel.

Conclusión

Los pacientes de con CCRm y TT en VCI pueden beneficiarse del tratamiento neoadyuvante con inhibidores de puntos de control inmunológico con o sin TKIs y NC diferida.

Introduction

Renal cell carcinoma (RCC) represents approximately 2%–3% of malignant tumors in adults.¹ According to GLOBOCAN, the annual mortality rate in 2022 was 23.07%.²

The advent of systemic therapies —initially with tyrosine kinase inhibitors (TKIs) and more recently with immune checkpoint inhibitors (ICIs)— has led to significant improvements in survival, along with the reduction in adverse events. These benefits are particularly notable in patients with metastatic (mRCC), as a favorable response to ICI-based therapy is considered a prognostic factor for sustained benefit following delayed cytoreductive nephrectomy (dCN).³

RCC involves the inferior vena cava (IVC) in approximately 4%–10% of de novo cases. Patients with RCC with TT extending into IVC represent a complex group of patients, even in the absence of metastatic disease, due to the altered surgical anatomy that increases the risk of surgical complications and may adversely affect oncologic outcomes. Current evidence for this particular patient population is limited, and there are no international guidelines that standardize treatment and follow-up, especially after the implementation of immunotherapy, which is still under investigation.^4,5

This review is focused on the oncologic and surgical outcomes of patients with mRCC and IVC tumor thrombus treated with neoadjuvant immunotherapy, with or without targeted therapy, followed by deferred cytoreductive nephrectomy.

Material and methods

Inclusion criteria

• •

  Experimental and observational studies. Systematic reviews, real-life studies, case reports, and case series.

• •

  Population of interest: patients with mRCC and vena cava tumor thrombus.

• •

  Intervention: Immune checkpoint inhibitor therapy with or without TKIs and cytoreductive nephrectomy.

• •

  From 2018 to June 2024, English and Spanish language.

Exclusion criteria

• •

  Studies that do not specify the presence of tumor thrombus in the vena cava, or that include thrombus limited only to the renal vein or the atrium.

• •

  Intervention: TKIs monotherapy or chemotherapy.

• •

  Articles that cannot be retrieved in full text, are in press, or exist only as preprints.

Keywords

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  Metastatic Renal Cell, mRCC, Checkpoint inhibitors, ICI, Target therapy, IOVEGF, Venous Tumor Thrombus, Checkpoint inhibitor combination therapies, cytoreductive nephrectomy, IPI-NIVO, IO-VEGF, VEGF-TT, ICI-TKI.

According to the Manual Standards for the Conduct of new Cochrane Intervention Reviews (MECIR). In stage I: Screening, stage II: Abstract analysis and stage III: Full text analysis — conducted independently by two investigators following standardization (Details in tesiunam).

Registration of the study selection process

• •

  Data extraction was performed in duplicate and independently in an Excel template.

Results

The search protocol was applied using the Digital Library of the School of Medicine of the National Autonomous University of Mexico (UNAM). The electronic databases consulted were PubMed, Ovid, Scopus, LILACS, ScienceDirect, Web Of Science, SpringerLink and CINAHL. Gray literature was reviewed through Google and Google Scholar. The reference lists of included articles were hand-searched for relevant studies.

A total of 2326 articles were identified from electronic databases, and 5 articles were found through manual and gray literature searches. After removing duplicates, 408 records remained. Of these, 224 were selected based on title and reviewed by abstract, resulting in 42 eligible articles for full-text review. Ultimately, 17 studies met the eligibility criteria (Fig. 1): 1 retrospective cohort, 5 retrospective case series and 11 retrospective case reports. Given the nature of the available data and the lack of clinical trials in this patient population, an exploratory systematic review methodology was applied.⁶

Figure 1.

Electronic libraries consulted: PubMed, Ovid, Science Direct, Scopus, Lilacs, WEB OF SCIENCE, Springer Link, CINAHL. Other sources: Google, Google scholar. Manual search in references of articles included in the review.

The retrospective cohort published by Abhenil Mittal et al. 2023 includes 226 patients with mRCC of whom 64 had TT. Among these, 55 were treated with TKIs, three with chemotherapy, and six with ICIs (five with dual ICI therapy and one with a combination of ICI and TKIs). However, tumor response was evaluated only in 12 patients. These patients are not included in the review because, although they meet the selection criteria, the treatment they received was not specified.⁷

Considering the series and case reports, a total of 32 patients were identified. Of these, 10 patients from the case series were classified as "non-metastatic" and were excluded because they did not meet the population criteria (Tables 1 and 2).

Table 1.

Characteristics of patients with mRCC and IVCTT treated with immunotherapy, with or without tyrosine kinase inhibitors.

Reference	N	Age Sex	Treatment	Laterality	Renal mass after systemic treatment	IVC tumor thrombus
						Initial	Pre-surgical
Berends J 2019^22	1	47 M	sunitinib, nivolumab CN	Two confluent RR 91 and 142 mm	114 mm	II-III	I
Bender L 2019^17	2	87 M	nivolumab without surgical treatment	RR 122.5 mm	82 mm [↓67%]	IV 36 × 20 mm	IV ↓ the size
Shepherd ARH 2019^23	3	61 M	ipilimumab, nivolumab CN, thrombectomy	RR 90 mm	50 mm	III	II ↓ size and extent
Bhat A 2019^12	4	57 F	pazopanib, nivolumab nivolumab, cabozantinib CN and thrombectomy	RR [NR]	70 mm	IV	II
Okada T 2020^13	5	47 M	nivolumab, ipilimumab CN and Thrombectomy	LR 150 mm	70 mm	III	↓?
Nishimura K 2021^11	6	71 F	nivolumab, ipilimumab/ pazopanib CN and Thrombectomy	RR 94 mm	84mm	IV 37 mm	III
Otsuka H 2022^24	7	67 M	nivolumab, ipilimumab CN and thrombectomy	RR 137 × 95 mm		IV	I
Yoshida K 2022^20	8 9 10 11	(1) 48H (2) 67M (4) 72H (5) 72M	(1) nivolumab, ipilimumab (2) pembrolizumab, (4) axitinib, nivolumab, ipilimumab, without CT (5) nivolumab, ipilimumab without surgical treatment	(1−5) [NR]	(1) ↓ 37 mm [36%]. (2) ↓ 19 mm [26%]. (4) ↓40 mm [36%] (5) ↓ 56 mm [48%].	(1) IV (2) II (4) II (5)II	(1) III [↓44 mm (34%)] (2) I [↓39 mm (48%)] (4) I [↓20 mm (36%)]
							(5) II [↓37 mm (55%)]
Nellowe C 2023^8	12 13 14	(1) 68H (4) 58H (5) 70M	(1) lenvatinib, pembrolizumab (4) pembrolizumab, axitinib /cabozantinib (5) pembrolizumab, axitinib (1−4) CN thrombectomy without surgical treatment	(1) RR 118 × 96 × 114 mm (4) RR 120 × 80 mm (5) LR [NR]	(1) NR (4) [NR] (5) [NR]	(1) II 41 × 46 mm (4) III 44 × 48 mm (5) II	(1) II [36 × 37 mm]. ↓21.7%
							(4) II [2.2 × 2.2 cm]. ↓54.16%
							(5) II ↓26.5%.
Yoshino H 2023^10	15	(3) 70H	(3) nivolumab, ipilimumab	(3) LR [NR]	(3) [NR]	(3) II	(3) I
Takahara K 2023^21	16	64 F	pembrolizumab, lenvatinib all CN	RR [NR]	[NR]	(4) II	(4) I
Urabe F 2023^9	17 18	(1) 51H (2) 71H	(1) pembrolizumab, axitinib (2) pembrolizumab, axitinib All CN	(1) LR [NR] (2) RR [NR]	(1) ↓78% (2) ↓ 25% 116 × 96 × 83	(1) I (2) I	(1) I ↓57% (2) 0 ↓ 100%
Alhamdani Z 2023^18	19	30 F	nivolumab, ipilimumab cabozatinib thrombolysis, thrombectomy, thrombectomy without surgical treatment	LR [NR]	↓?	II	?
Nagahisa C 2024^25	20	73 M	lenvatinib, CN	RR [NR]	↓?	IV	II
Hara T 2023^26	21	61 M	lenvatinib, CN, thrombectomy	RR 45 mm	↓25 mm	III	III
Nicaise EH 2024^27	22	41 M	nivolumab, ipilimumab CN lenvatinib, /Denosumab radiation therapy/ belzutifan	RR 95 × 82 × 68 mm	88 × 63 × 87 mm	III	IV

Male M, Female F, Cytoreductive nephrectomy CN, Complete response CR, Right renal laterality RR, Left renal LR, Not reported NR. No size specified? Improvement marked in red, no change marked in yellow, and progression marked in green.

Table 2.

IMDC risk and follow-up of patients with mRCC and IVCTT treated with immunotherapy, with or without targeted therapy.

Reference	IMDC risk	Metastasis after systemic treatment	Surgical site pathology	Post-nephrectomy Follow-up	Surgical time (minutes) Bleeding (ml)	Adverse events
Berends J 2019^22	[NR]	Lung, partial regression, retroperitoneal lymph node from 27 to 17 mm and iliac	[NR]	Without recurrences no time is specified.	[NR]	Dehydration, hypercoagulability, and portal system, mesenteric and splenic veins thrombosis
Bender L 2019^17	[NR] ECOG 1	Lung partial regression	[NR]	No intervention due to persistent TT level.	----	[NR]
Shephered ARH 2019^23	Intermediate	Liver, lungs, right acetabulum (regression)	No viable cells in thrombus or primary tumor	[NR]	[NR]	[NR]
Bhat A 2019^12	Intermediate	Full resolution Hepatics	No viable cells in either primary tumor or TT. No evidence of residual disease	[NR]	[NR]	Bleeding duodenal ulcer
Okada T 2020^1^3	Intermediate	Lung complete response	No residual tumor, no viable cells in PT or TT	No recurrence or additional treatment 8 months	NR	Diarrhea
Nishimura K 2021^11	Poor	Undetectable pulmonary	Residual tumor in primary tumor 10–20% none in TT viable cells in TT none	remained clinically free of disease one year after surgery, with no evidence of recurrence or metastasis.	540 min 3000 ml	NR
Otsuka H 2022^24	Poor	Pulmonary shrinkage and mediastinal lymphadenopathy	Residual viable cells in primary tumor and TT	1 year: stable pulmonary metastases	182 min 375 ml	Skin rash fever
Yoshida K 2022^20	(1) 5 FR (2) 4 FR (4) 4 FR (5) 5 FR (1,2,4,5) Poor	(1, 2) CR RX lung (4) CR RX lung RX lymph node (5) brain, lymph node increased in Lung	Viable tumor cells persisted in all cases.	(1) Developed in brain (20 months) (2,) 13 months, (4) 8 months: without disease (5) lung metastases reduced disease in progress (18months) (4.5) without surgical treatment	(1,2,3) 329 min 1479 ml	(1) None (2) None (4) Hypopituitarism (5) Rash
Nellowe C 2023^8	[NR]	(1) Osseous, Retroperitoneal adenopathies (4) External iliac adenopathy, lung (5) lung and retroperitoneal lymph nodes	(1, 4) viable cells +	(1.4) recovery without long-term surgical complications (5) without surgical treatment	(1,4) NR	(1) Hypertension, rash, proteinuria (4) hypertension, proteinuria (5) Abdominal hematoma, immune encephalitis
Yoshino H 2023^10	[NR]	(3) left adrenal gland	(3) negative surgical margin	(3) 18 months without recurrences:	(3)604 min 725 ml	(3) hypothyroidism
Takahara K 2023^21	[NR]	(4) lung	(4) negative surgical margin	[NR]	(4)286 min, 604 ml	(4) None
Urabe F 2023^9	[NR]	(1,2) Complete lung response	negative surgical margin Viable cells + (1) 5%TT and 0% PT (2) 5%TT, 20%PT	Progression-free survival 11 months	(1)431 min 4,380 ml (2)259 min 90 ml	(1,2) None
Alhamdani Z 2023^18	[NR]	Bone, hepatic, lymph node [NR] progression	[NR]	[NR]		Bilateral submassive pulmonary embolism (PE) and heart failure
Nagahisa C 2024^25	Poor 3 factors	Pulmonary	viable PT and TT cells	8 months free of recurrence	434 min 135 ml	Hypertension, diarrhea stomatitis
Hara T 2023^26	Intermediate	Ribs ↓ (56 to 36 mm)	No viable cells PT, TT	5 months without treatment	434 min 135ml	hypertension, diarrhea, stomatitis
Nicaise EH 2024^27	Intermediate risk	Progression of pulmonary and hepatic metastases. Tumor thrombus extended into the right atrium.	Clean surgical margin, free of viable cells	Progression of metastases is different systemic treatments and is participating in an experimental study.	[NR]	Hypothyroidism, palmoplantar erythrodysesthesia Oral mucosal ulcers Fatigue

International Metastatic Renal Cell Carcinoma Database Consortium (IMDC), Eastern Cooperative Oncology Group (ECOG), Cytoreductive nephrectomy CN, Complete response CR, Not reported NR. PT primary tumor, TT tumor thrombus, minutes min.

This systematic review included 22 patients with mRCC and IVCT who received neoadjuvant treatment with ICI, with or without TKIs. There were 7 women and 15 men, with median and P₂₅₋₇₅ age of 67 (57–71) and 61 (48–71), respectively. Clear cell carcinoma was reported in 19 patients, while histology was not reported in 3 cases.

Reported adverse events related to systemic treatment were dehydration, hypercoagulability with thrombotic processes, duodenal ulcer bleeding, diarrhea, skin rash, fever, liver dysfunction, hypopituitarism, hypertension, proteinuria, hypothyroidism, hand-foot syndrome, dysphonia, arthralgia, fatigue, abdominal hematoma, immune encephalitis, constipation, pulmonary embolism, heart failure, stomatitis, oral mucosal ulcers. (Table 2)

Of the patients who underwent nephrectomy with thrombectomy, 9 did not report surgical time or blood loss. Among the remaining 8 patients, surgical time was (_median; p₂₅₋₇₅) 342 (273–530) minutes and blood loss was 856 (604–2650) ml. Reported surgical complications included one case of hydropneumothorax and one case of shock. No deaths were reported. In 5 patients, nephrectomy was not performed (Table 2).

Nellowe C. et al. reported 5 cases, of which 2 were non-metastatic and were therefore excluded. In case 5, one month after initiating neoadjuvant treatment, the patient developed a non-traumatic abdominal wall hematoma. Despite continuation of 2 additional cycles, the patient developed immune encephalitis, with no improvement to steroid treatment.⁸

Two cases were included from the series of Fumihiko Urabe et al. (2023). The median follow-up after nephrectomy was 23 months (range 19–30). In all cases, thrombus size decreased, and in 3 cases, the level decreased. In all cases adhesions were found during surgery, but did not cause complications. One patient presented abdominal lymphatic leakage within 90 days after surgery. The median progression-free survival (PFS) was 11 months (95% CI 5.5–22.5).⁹

Hirofumi Yoshino (2023) published a case series of three patients, including case 3, a diabetic patient with concurrent nephropathy.¹⁰

Kenichi Nishimura (2021) reported that the patient had a Karnofsky Performance Status of 40, prompting initiation of preoperative systemic therapy, which resulted in sufficient clinical improvement to permit surgery.¹¹

In the case reported by Abhishek Bhat in 2019, metastatic renal cell carcinoma (mRCC) coexisted with pulmonary embolism and retroperitoneal lymphadenopathy, for which the patient was treated with apixaban. Treatment with pazopanib was initiated, later switched to nivolumab. The patient subsequently presented with upper gastrointestinal bleeding secondary to a duodenal ulcer. Six months later, a decrease in the size of the primary renal mass was observed, but the extension of the tumor thrombus persisted, with development of new hilar lymphadenopathy and segmental pulmonary embolism. He continued with nivolumab, and three months later, further reduction of the renal mass and thrombus was observed only at the liver level, with new suspicious masses in the liver. Cabozantinib and nephrectomy were added.¹²

Regarding the size of the renal mass and IVC TT at diagnosis and before surgery, it was not possible to make a quantitative synthesis because some authors report larger diameter, transverse diameter and even 3 diameters. In most cases, the size of the primary tumor decreased. Regarding the level of vena cava tumor thrombus (TT) in the 22 patients, 7 remained unchanged, in 13 it decreased (in 9 by one level, in 3 by two levels, and in 1 by three levels), and in 1 it increased. The report was unclear in 1 patient, who omitted the second measurement.¹³ As for the size of the tumor thrombus, even in those who did not show a change in level, a decrease in size was recorded (Tables 1 and 2).

Discussion

The decision between initiating neoadjuvant therapy followed by nephrectomy with thrombectomy or proceeding with surgery first and administering systemic treatment afterward, depends on various clinical factors and the patient's overall condition.

Neoadjuvant ICIs therapy with or without TKIs, can reduce the size of the primary tumor and tumor thrombus (TT), potentially resulting in less invasive surgery and a lower risk of complications. In non-metastatic patients, however, the risk of disease progression during systemic therapy is considered a limitation. In contrast, in metastatic patients, in addition to favorable responses in the primary tumor and TT, neoadjuvant therapy may help control metastatic disease prior to surgery. In cases with significant obstruction or thrombus-related complications, initial surgery provides immediate local control of the tumor and thrombus, which can be critical in such scenarios. However, in patients with advanced metastatic disease, upfront surgery carries a high risk and may not adequately address systemic disease progression.¹⁴

In 2009, four cases of metastatic renal cell carcinoma (mRCC) with tumor thrombus (TT) treated with radical nephrectomy were reported. One patient died intraoperatively due to ventricular failure; two died postoperatively from coagulopathy and systemic inflammatory response syndrome. The remaining patient had a survival of six months. Two cases were classified as level III thrombus and two as level IV.¹⁵

In 2003, 5 mRCC patients with initial surgical treatment were reported, 3 died 12 months later and 2 in the immediate postoperative period. Of these two, one died due to massive hemorrhage, and the other one died 6 days after surgery due to upper gastrointestinal bleeding.¹⁶

The cases analyzed in this review were predominantly male, with an average age of 61 years, generally presenting with poor prognosis, level III–IV tumor thrombus, or clinical conditions that increased the risk of immediate surgical treatment. These patients were managed with immunotherapy, either alone or in combination with TKIs, followed by deferred surgery. Although it is hypothesized that neoadjuvant treatment may increase adhesions and necrotic tissue that could complicate surgery, there is currently insufficient objective data to support or refute this concern. Qualitatively, some authors reported the presence of adhesions, though without noting associated surgical complications. Metastatic response was mostly favorable, with reduction in the primary tumor, thrombus size, and thrombus level—facilitating reduced surgical risk. The persistence of viable cells at the surgical site varied. Medium- and long-term follow-up data remain insufficient to draw conclusions regarding prognosis.

The case reported by Bender et al. was treated with ICIs for 7 months, did not undergo surgery due to persistent adherence of the thrombus to the lateral wall of the IVC and renal vein, despite obtaining a reduction of pulmonary metastases, of the primary tumor and a partial regression of thrombus size, but with no impact on the level.¹⁷

Case 5, presented by Nellowe C et al., was complicated by encephalopathy, for which he was provided with palliative care.⁵

In the case presented by Zein Alhamdani, initiation of IO therapy was complicated by a pulmonary embolism. It is discussed whether it was an adverse effect or secondary to necrosis of the IVC tumor thrombus. There was also a history of venous and arterial thrombotic events occurring six months after the start of IO therapy. CN was not performed due to adherence of the kidney to the surrounding vessels and main structures; however, thrombectomy was performed with subsequent identification of residual thrombus three weeks later, when treatment with cabozantinib was started.¹⁸

The adverse events reported for neoadjuvant therapy are consistent with those described in the literature; the most relevant were immune-mediated encephalitis, pulmonary embolism, portal system embolism, hepatic insufficiency, which could have affected patient outcomes and even prevented surgery. Preventive measures could be considered for dehydration and bleeding duodenal ulcer.¹⁹

The omission of the IMDC (International Metastatic RCC Database Consortium) in more than half of the reports is striking; however, it is evident that the higher the level of tumor thrombus, the more complex the approach will be.

In general, the surgical data are limited; in 33% of cases, neither operative time nor intraoperative blood loss was reported. Among the eight patients with available data, surgical time ranged from 273 to 530 minutes in 50% of cases, with estimated blood loss between 604 and 2,650 mL. These prolonged operative times and significant blood loss are consistent with the high complexity of procedures in patients with advanced-level tumor thrombi.¹⁶

Currently, there are no published controlled clinical trials or cohort studies evaluating preoperative therapy with ICIs, alone or in combination with TKIs, in patients with tumor thrombus in the vena cava and mRCC. This decision should be individualized, considering factors such as the patient’s overall condition, thrombus extension, metastatic burden, and the experience of the treating team. Multidisciplinary collaboration among oncologists, urologists, and cardiovascular surgeons is essential to optimize outcomes.

Conclusion

Patients with mRCC and TT in IVC may benefit from neoadjuvant treatment with immune checkpoint inhibitors, with or without TKIs, followed by deferred CN.

Limitations and strengths

A potential limitation of this review is publication bias, which may lead to an overestimation of outcomes, as the available data are primarily derived from case reports and case series. Another significant limitation is the omission of key variables in many reports, such as the International Metastatic RCC Database Consortium (IMDC) risk classification, size of the primary tumor or tumor thrombus, surgical time, and estimated blood loss.

There is also a lack of standardization in how the size of the primary tumor and tumor thrombus is measured and reported, which limits comparability across studies.

To date, no studies have included patients with mRCC and TT treated with ICIs who were eligible for initial nephrectomy followed by systemic therapy. The patients described in the literature were not candidates for upfront nephrectomy and therefore received systemic therapy as the initial approach. For this reason, conducting a clinical trial to evaluate the impact of initial versus deferred nephrectomy in this specific population may not be feasible.

The omission of important data, which should be considered in future studies to achieve standardization of results, is notable. This research provides useful information for oncologists and urologists to make shared decisions with informed patients. By disseminating the results of this work, we hope to stimulate prospective cohort studies in this population receiving neoadjuvant immunotherapy.