Probability of Downsizing Primary Tumors of Renal Cell Carcinoma by Targeted Therapies Is Related to Size at Presentation

Kroon, Bin B. R.; Bruijn, Roderick de; Prevoo, Warner; Horenblas, Simon; Powles, Thomas; Bex, Axel

doi:10.1016/j.urology.2012.09.014

Cited by 20 publications

(13 citation statements)

References 18 publications

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“…In addition, response to sunitinib could serve as a means of selecting patients who would be most likely to derive benefit from this drug after cytoreductive nephrectomy. Recently, published case reports and series have shown evidence that tyrosine kinase inhibitors can downstage advanced primary tumors to facilitate surgery [23,24,25]. Our observations confirm that sunitinib may prove useful in the neoadjuvant setting, by facilitating surgical procedures, which otherwise would not be feasible.…”

Section: Discussionsupporting

confidence: 80%

Retroperitoneal Laparoscopic Nephrectomy Combined with Bench Surgery and Autotransplantation for Renal Cell Carcinoma in the Solitary Kidney or Tumor Involving Bilateral Kidneys: Experience at a Single Center and Technical Considerations

Li²,

Shao³

et al. 2016

Urol Int

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Objective: To assess the feasibility of retroperitoneal laparoscopic nephrectomy combined with bench surgery and autotransplantation in treating complex renal tumor. Patients and Methods: Six patients with complex renal tumor were seen in our institution between 2010 and 2014. Three patients with bilateral renal cell carcinoma underwent retroperitoneal laparoscopic nephrectomy on both sides. Extracorporeal tumorectomy and renal reconstruction were performed on the side of the smaller tumor and then kidney autotransplantation was performed. The other 3 patients with tumor involving the solitary kidney underwent laparoscopic nephrectomy combined with bench surgery and autotransplantation. Result: The total time of the operation was 287 ± 25 min; warm ischemia time 3.1 ± 0.7 min; cold ischemia time 47 ± 8.1 min; and kidney autotransplantation required time 86 ± 8.6 min. Estimated blood loss was 232 ± 45.8 ml. Serum creatinine levels were 179 ± 44.7 µmol/l upon hospital discharge. Two patients received temporary hemodialysis. No patient needed further hemodialysis during follow-up. One patient died of multiple metastases 18 months after surgery. The other 5 patients survived without recurrence or metastasis during follow-up. Conclusions: Retroperitoneal laparoscopic radical nephrectomy combined with bench surgery and autotransplantation is a feasible choice for patients with complex renal cell carcinoma in bilateral kidneys and tumor involving the solitary kidney.

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Section: Discussionsupporting

confidence: 80%

Retroperitoneal Laparoscopic Nephrectomy Combined with Bench Surgery and Autotransplantation for Renal Cell Carcinoma in the Solitary Kidney or Tumor Involving Bilateral Kidneys: Experience at a Single Center and Technical Considerations

Li²,

Shao³

et al. 2016

Urol Int

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“…This may result from large fibrotic or necrotic components that may not change during therapy. Alternatively, the change of tumour volume which is necessary before a 20% increase or 30% decrease in diameter is detected may not be achievable for many large lesions within the treatment period [13]. However, 82% (94/115) of metastases were of small or intermediate size.…”

Section: Resultsmentioning

confidence: 99%

Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma

Crusz

Tang

Sarker

et al. 2016

BMC Med

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BackgroundMolecular intratumour heterogeneity (ITH) is common in clear cell renal carcinomas (ccRCCs). However, it remains unknown whether this is mirrored by heterogeneity of drug responses between metastases in the same patient.MethodsWe performed a retrospective central radiological analysis of patients with treatment-naïve metastatic ccRCC receiving anti-angiogenic tyrosine kinase inhibitors (TKIs) (sunitinib or pazopanib) within three similar phase II trials. Treatment was briefly interrupted for cytoreductive nephrectomy. All patients had multiple metastases that were measured by regular computed tomography scans from baseline until Response Evaluation Criteria In Solid Tumours (RECIST)-defined progression. Each metastasis was categorised as responding, stable or progressing. Patients were classed as having a homogeneous response if all lesions were of the same response category and a heterogeneous response if they differed.ResultsA total of 115 metastases were assessed longitudinally in 27 patients. Of these patients, 56% had a heterogeneous response. Progression occurred through the appearance of new metastases in 67%, through progression of existing lesions in 11% and by both in 22% of patients. Despite RECIST-defined progression, 57% of existing metastases remained controlled. The sum of controlled lesions was greater than that of uncontrolled lesions in 47% of patients who progressed only with measurable new lesions.ConclusionsWe identified frequent ITH of anti-angiogenic TKI responses, with subsets of metastases responding and progressing within individual patients. This mirrors molecular ITH and may indicate that anti-angiogenic drug resistance is confined to subclones and not encoded on the trunk of the tumours’ phylogenetic trees. This is clinically important, as patients with small-volume progression may benefit from drug continuation. Predominant progression with new rather than in existing metastases supports a change in disease biology through anti-angiogenics. The results highlight limitations of RECIST in heterogeneous cancers, which may influence clinical trial data validity. This analysis requires prospective confirmation.Trial registrationEuropean Clinical Trials Database(EudraCT): 2009-016675-29, registered 17 March 2010; EudraCT: 2006-004511-21, registered 09 March 2007; EudraCT: 2006-006491-38, registered 22 December 2006.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-016-0729-9) contains supplementary material, which is available to authorized users.

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“…This effect was observed in the present study, during which, the level of the tumor thrombus was decreased following sunitinib treatment, including two cases that were downgraded from tumor thrombus level IV to II, one case from level IV to III and two cases from level III to II. The majority of previous studies have demonstrated that targeted therapy is able to downsize RCC tumors in order to allow organ-sparing surgeries to be performed (11,17), including a partial nephrectomy for patients with localized and advanced RCC (18). Downstaging may also decrease the risk of recurrence (10).…”

Section: Discussionmentioning

confidence: 99%

“…The ESMO guidelines recommend a period of early observation following diagnosis (21). Bex et al (17) reported that the indications for neoadjuvant targeted molecular therapy include RCC with vena cava tumor embolus level III/IV and RCC at the tumor-node-metastasis system stage T1b or T2 as suitable for partial nephrectomy (bilateral RCC or solitary kidney) or as tentative therapy for advanced RCC prior to cytoreductive surgery (18,19). For patients with tumor embolus level III or lower, presurgical neoadjuvant targeted molecular therapy may be considered to reduce tumor size if the imaging examinations suggest that resection is impossible due to the tumor embolus being adhered to the vena cava wall (12).…”

Section: Discussionmentioning

confidence: 99%

Presurgical neoadjuvant targeted molecular therapy for kidney cancer with concomitant vena cava tumor embolus: A clinical study

Guo¹,

Cai²,

Li³

et al. 2017

Oncology Letters

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Abstract. The present study aimed to investigate presurgical neoadjuvant targeted therapy for patients with kidney cancer and vena cava tumor embolus, in order to examine its indications, therapeutic effects and optimal timing of surgery. Between June 2009 and June 2014, 12 patients from The People's Liberation Army General Hospital (Beijing, China) were diagnosed with kidney cancer with superior vena cava tumor embolus, and received presurgical neoadjuvant targeted therapy (sorafenib 400 mg twice a day or sunitinib 50 mg/day) for a median of 13.3 weeks. Patients included 8 males and 4 females, with a median age of 49.8 years.Kidney cancer was present on the left side in 3 patients and in the right side in 9 patients. The median tumor embolus length was 9.7 cm (range, 6.5-14.0 cm). Tumor embolus levels II, III and IV, classified by the Mayo Clinic standard, were observed in 2, 6 and 4 patients, respectively. Median treatment time and average targeted therapy discontinuation time were observed to be longer in sunitinib-treated patients compared with sorafenib-treated patients. In total, 2 patients in the present study had partial remission (PR) and 8 patients had stable disease (SD); for tumor embolus, 4 patients had PR and 8 patients had SD. Tumor embolus length decreased by a median value of 18.7% (range, 0.0-42.1%) or 1.8 cm (range, 0.1-5.2 cm). Tumor diameter decreased by a median value of 8.6% (range, 0.0-38.9%) or 0.7 cm (range, 0.0-3.5 cm). The level of the tumor thrombus, classified by the Mayo Clinic standard, was observed to decrease following sunitinib treatment, including two cases downgraded from tumor thrombus level IV to II, one case from level IV to III and two cases from level III to II. Presurgical neoadjuvant targeted molecular therapy may have the potential to reduce the tumor stage of patients, as well as decreasing the surgical difficulty for radical nephrectomy.

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Probability of Downsizing Primary Tumors of Renal Cell Carcinoma by Targeted Therapies Is Related to Size at Presentation

Cited by 20 publications

References 18 publications

Retroperitoneal Laparoscopic Nephrectomy Combined with Bench Surgery and Autotransplantation for Renal Cell Carcinoma in the Solitary Kidney or Tumor Involving Bilateral Kidneys: Experience at a Single Center and Technical Considerations

Retroperitoneal Laparoscopic Nephrectomy Combined with Bench Surgery and Autotransplantation for Renal Cell Carcinoma in the Solitary Kidney or Tumor Involving Bilateral Kidneys: Experience at a Single Center and Technical Considerations

Heterogeneous response and progression patterns reveal phenotypic heterogeneity of tyrosine kinase inhibitor response in metastatic renal cell carcinoma

Presurgical neoadjuvant targeted molecular therapy for kidney cancer with concomitant vena cava tumor embolus: A clinical study

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