Clinical Investigation
Long-Term Outcomes After Maximal Surgical Resection and Intraoperative Electron Radiotherapy for Locoregionally Recurrent or Locoregionally Advanced Primary Renal Cell Carcinoma

Presented at the 6th International Conference of the International Society of Intraoperative Radiation Therapy, Scottsdale, AZ, Oct 14–16, 2010, and at the American Society for Therapeutic Radiology and Oncology 52nd Annual Meeting, San Diego, CA, October 31–November 4, 2010.
https://doi.org/10.1016/j.ijrobp.2011.02.026Get rights and content

Purpose

To report outcomes of a multimodality therapy combining maximal surgical resection and intraoperative electron radiotherapy (IOERT) for patients with locoregionally (LR) recurrent renal cell carcinoma (RCC) after radical nephrectomy or LR advanced primary RCC.

Methods and Materials

From 1989 through 2005, a total of 22 patients with LR recurrent (n = 19) or LR advanced primary (n = 3) RCC were treated with this multimodality approach. The median patient age was 63 years (range 46-78). Twenty-one patients (95%) received perioperative external beam radiotherapy (EBRT) with a median dose of 4,500 cGy (range, 4,140–5,500). Surgical resection was R0 (negative margins) in 5 patients (23%) and R1 (residual microscopic disease) in 17 patients (77%). The median IOERT dose delivered was 1,250 cGy (range, 1,000–2,000). Overall survival (OS) and disease-free survival (DFS) and relapse patterns were estimated using the Kaplan–Meier method.

Results

The median follow-up for surviving patients was 9.9 years (range, 3.6–20 years). The OS and DFS at 1, 5, and 10 years were 91%, 40%, and 35% and 64%, 31%, and 31%, respectively. Central recurrence (within the IOERT field), LR relapse (tumor bed or regional lymph nodes), and distant metastases at 5 years were 9%, 27%, and 64%, respectively. Mortality within 30 days of surgery and IOERT was 0%. Five patients (23%) experienced acute or late National Cancer Institute Common Toxicity Criteria (NCI-CTCAE) Version 4 Grade 3 to 5 toxicities.

Conclusions

In patients with LR recurrent or LR advanced primary RCC, a multimodality approach of perioperative EBRT, maximal surgical resection, and IOERT yielded encouraging results. This regimen warrants further investigation.

Introduction

In the United States, approximately 58,240 patients were diagnosed with cancer of the kidney or renal pelvis in 2010 (1). The majority of patients with this disease present with clinically localized renal cell carcinoma (RCC) and are candidates for potentially curative nephrectomy. However, some patients present with locoregionally advanced disease of borderline resectability. In addition, 1% to 3% of patients experience isolated locoregional (LR) recurrence in the retroperitoneal soft tissue and/or nodal basins after nephrectomy 2, 3, 4, 5. The optimal management of isolated LR recurrent disease remains unknown, given its relative infrequency. In carefully selected patients with resectable LR recurrent disease, salvage surgery is associated with long-term survival in only a small portion of patients 2, 3, 4, 5, 6, 7, 8, 9. In the setting of salvage or primary surgery, margin status was reported to be an important prognostic factor for survival 4, 10. However, a wide resection of tumor is often unachievable due to its close proximity or frank invasion into adjacent unresectable structures such as major vessels and/or vertebral bodies. Therefore, in patients with LR recurrence or LR advanced primary RCC of borderline resectability, it is appropriate to consider additional LR therapies adjunct to surgery to optimize LR control and survival.

Since 1989, we have treated selected patients with isolated LR recurrence after nephrectomy or LR advanced primary RCC with a multimodality approach consisting of perioperative external beam radiotherapy (EBRT), maximal resection, and intraoperative electron radiotherapy (IOERT). In 1994, we reported favorable early outcomes in an initial cohort of patients (11). In addition, we have reported high rates of local control and acceptable toxicity with this multimodality approach for patients with other LR advanced primary or LR recurrent abdominal and pelvic tumors 12, 13, 14, 15, 16, 17. Here we report long-term outcomes on an expanded series of patients with LR recurrence or LR advanced primary RCC treated with a multimodality approach incorporating IOERT.

Section snippets

Methods and Materials

The prospective departmental IORT database was searched for patients with RCC treated with IOERT at Mayo Clinic, Rochester, MN. Inclusion criteria included primary or recurrent RCC treated with surgery and IOERT to LR disease as a component of potentially curative therapy. Exclusion criteria included surgery and IOERT to a distant metastatic site for palliation of symptoms only. Twenty-two consecutive patients treated between 1989 and 2005 met the above criteria and were included in this

Results

Patient characteristics are detailed in Table 1. Three patients had LR advanced primary disease with extensive retroperitoneal nodal involvement, pancreas involvement, or nephrectomy with positive margins at an outside institution. Nineteen patients had an LR recurrence in the retroperitoneal soft tissue and/or lymph nodes at a median interval of 2.0 years (range, 0.7–13.7 years) after nephrectomy (Fig. 1). Eighteen patients were treated for first recurrence and 1 patient was treated for a

Discussion

The optimal management of LR recurrent or LR advanced primary RCC is unknown. In selected patients with LR recurrence, salvage surgery has been performed 2, 3, 4, 5, 6, 7. However, in many patients, a wide margin resection is difficult to achieve because tumor is intimately associated with critical, unresectable structures. Therefore, despite resection of all gross disease, patients are at high risk for further relapse and death 2, 3, 4, 5, 6, 7. In an effort to optimize LR control for patients

Conclusion

To our knowledge, our study represents the largest series examining a potential utility of the multimodality therapy consisting of perioperative EBRT, maximal surgical resection, and IOERT for patients with LR recurrent or LR advanced primary RCC. With mature follow-up, this treatment approach was associated with a low rate of LR recurrence, acceptable toxicity, and long-term survival in a significant number of patients. This regimen warrants further investigation to better define appropriate

References (29)

Cited by (19)

  • Local Recurrence After Curative Surgical Treatment of Renal Cell Cancer: A Study of 91 Patients

    2016, Clinical Genitourinary Cancer
    Citation Excerpt :

    To enhance the local therapeutic effect, patients at high risk of positive surgical margins in our study were offered IORT (18.7%). IORT, in addition to surgery, for LR has been proposed to improve local tumor control, especially in patients with LR who have a high risk of incomplete resection.21,22 Seventeen patients underwent surgery combined with IORT, 13 (76%) of whom had negative margins at the final pathologic examination.

  • Kidney and Ureteral Carcinoma

    2015, Clinical Radiation Oncology
  • Radiotherapy for renal-cell carcinoma

    2014, The Lancet Oncology
    Citation Excerpt :

    Accordingly, findings from other retrospective studies have shown a significant reduction in local recurrence rate after adjuvant irradiation of pT3 tumours to conventionally fractioned doses of 41·4–63·0 Gy.37–39 Hallemeier and colleagues40 reported an update on 22 patients with primary locally advanced (14%) or recurrent (86%) disease who were treated with a multimodality approach of preoperative radiotherapy, surgical resection and intraoperative radiotherapy. Locoregional control at 5 years exceeded 60%, which compared favourably with historical series of patients given surgery alone for recurrent disease.

  • Outcomes in a multi-institutional cohort of patients treated with intraoperative radiation therapy for advanced or recurrent renal cell carcinoma

    2014, International Journal of Radiation Oncology Biology Physics
    Citation Excerpt :

    Similar to treating RCC metastases with radiosurgery, the large single-fraction dose provided by IORT may be particularly useful against a tumor that is commonly thought to be relatively radiation resistant (7). The addition of IORT in primary and recurrent settings has been previously reported in small single-institution cohorts, with encouraging initial results (8-12). In this study, we sought to examine prognostic factors and disease outcomes in a large pooled multi-institutional cohort of patients who received IORT for RCC.

View all citing articles on Scopus

Conflict of interest: none.

View full text