Individualised Kidney Cancer Surgery

A tailored approach

by Dr Tiong Ho Yee

The worldwide incidence of kidney cancer is increasing by about 2% to 3% per year and in the United States, more than 62,700 new cases are estimated by the American Cancer Society to occur in 2016 alone.1 This rising incidence of kidney cancer worldwide has been attributed to the increased detection of incidental kidney cancers picked up on the widespread use of cross-sectional imaging such as CT scans.

In Singapore, the incidence is 5.4 per 100,000 per year according to the Singapore Cancer Registry.2 The rates locally have also approximately doubled over the last 35 years. In Medical Grapevine, this author had previously discussed the state-of-the-art treatment armamentarium currently available at the National University Hospital (NUH) for both localised and advanced renal cell cancer in 2010 and 2013, respectively.3

Attention has now shifted to optimising not just the oncological outcomes for kidney cancer patients but also their long term renal function outcomes. The change in focus is due to the landmark description in the early 2000s of chronic kidney disease (CKD), defined as eGFR < 60 ml/min/1.73m2, and its association with cardiovascular morbidity and mortality.4 Therefore, increasingly, urologists need to collaborate with renal and primary care physicians to look after these patients’ kidney function after kidney cancer surgery, often many years down the road. Obviously, one size does not fit all. Since 2010, the NUH Urology Department has presented and published outcome studies by the author based on data from our local kidney cancer patient population. This article aims to share the findings with the community physicians to facilitate individualised care for local patients.

Renal function outcome

Just over 15 years ago, most urologists offered only radical nephrectomy to patients with a normal contralateral kidney regardless of the tumour size, with the thinking that the non-tumour bearing kidney would provide adequate renal function in a way similar to that in a kidney transplant donor. Kidney donors are carefully chosen, generally healthy, young with ample renal reserves but kidney cancer patients on the other hand represent a mixture of healthy and ill individuals. Interestingly we have found that a high base rate of CKD (24.8%) existed in our local kidney cancer patients even before surgery despite an apparently normal serum creatinine level.5 The same paper compared long term renal function outcome of patients undergoing radical and donor nephrectomy patients; not only were radical nephrectomy patients older with greater comorbidities, their lower pre-operative renal function significantly accelerates glomerular filtration rate (eGFR) deterioration in the uninephric state. However, for kidney cancer patients with minimal comorbidities and baseline eGFR of greater than 83 ml/min/1.73m2, their risk of acquiring CKD after nephrectomy is essentially the same as the kidney donors. For the community physicians, this information means that patients under their care post radical nephrectomy with lower pre-operative baseline renal function needs careful lifelong management of their blood pressure, diabetes, and proteinuria. It is also important that eGFR rather than creatinine levels alone is used to evaluate kidney function.

Indeed, nationwide databases in the United States hint towards the need for more holistic care of kidney cancer patients. Although the rates of kidney surgery have increased concurrently with the rising incidence of kidney cancer over the last two decades, all-cause mortality rates from patients with kidney cancer have not decreased.6 Such ‘treatment disconnect’4 may be due to the potential of surgical treatment by radical nephrectomy to increase post-operative CKD morbidity, which in turn increases associated competing causes of death. For example, up to a third of patients older than 70 years who are treated for kidney tumours have been found to die of other causes.7 There is therefore an increasing need to focus on improving the non-oncological outcomes of patients with

renal cancer.

In another publication by NUH last year, the remaining kidney volume as measured on pre-operative CT scan was shown to be an important surrogate marker for CKD after kidney cancer surgery.8 In fact patients with a remaining kidney volume of 144 cc or less were 2.8 times more likely to develop CKD after surgery than those with a greater volume than that (P=0.004).8 Furthermore, when compared to kidney donors, compensatory hypertrophy in the remaining kidney of kidney cancer patients after nephrectomy was a less frequent occurrence (79.3% vs. 29.3%, respectively).8,9 Hence, knowing that nephron mass is directly related to renal function, surgical strategies to optimise renal function would include preserving as much kidney tissue as possible, especially for localised renal cancers. At NUH, we have worked hard to develop and advance the use of laparoscopic partial nephrectomy with or without Da Vinci robotic assist for the treatment of this cancer.10 The minimally invasive option has the advantage of using advanced surgical technology to treat the localised kidney cancer with preservation of renal function and low surgical morbidity. Indeed, with 42 partial nephrectomies from 2013 to 2015, our data presented at the National Cancer Institute Singapore Annual Research Meeting 2015 (NCAM) reported no differences between minimally invasive (with or without robotic assist) and open partial nephrectomy in terms of renal function deterioration and cancer local recurrence.11

Oncological outcome

Despite the push for partial nephrectomy to treat localised kidney cancers, it is important to note that preserving renal mass must not come at a cost of oncological outcomes. To confuse the issue, in a randomised trial from Europe, there was no overall survival advantage for patients with kidney tumours of less than 5 cm treated with partial nephrectomy compared with radical nephrectomy.8 As there are multiple criticisms regarding the performance of this multi-center randomised controlled study, it is difficult to speculate why patients with improved renal function after partial nephrectomy did not do better than those after radical nephrectomy. At NUH, we believe that it is important to consider the morphological characteristics of the kidney tumor on CT to decide if partial nephrectomy (whether open or minimally invasive) can provide a good chance of cancer clearance. We were the first in Singapore to correlate the use of R.E.N.A.L Nephrometry Score (a standardised anatomical description of a renal mass) with the risk of pathological upstaging after surgery.13 In other words, kidney cancers that are clinically stage T1 but have high Nephrometry scores, there is a significant risk of that it is actually more advanced pathologically. Knowing this preoperatively, care should be taken to perform a thorough partial nephrectomy or even a radical nephrectomy. In addition, we have also noted different cancers with different aggressiveness may present with different metabolic signatures.14 At the moment we are unable to evaluate this through a kidney mass biopsy but are working in this direction so that for aggressive (high metabolic rate and high grade) lesions, the inclination would be to perform a radical nephrectomy rather than partial.

Figure-1

Figure 1. Summary of factors influencing the renal function and oncological outcomes of localised kidney cancer treatment

Strategy to individualise treatment to optimizeboth outcomes

In conclusion, we now possess medical evidence based on local population data to help us tailor a surgical approach for localised kidney cancer treatment. Figure 1 summarises the aforementioned factors that influence the balance between oncological and functional outcome for kidney cancer surgery. For a young and healthy patient with excellent kidney function, whether partial nephrectomy or radical nephrectomy is performed or not it is unlikely that significant long term medical renal damage will occur following either operation since these patients are akin to the healthy donor population. Focus should be placed on optimising oncological outcome and high Nephrometry cancers can be safely dealt with radical nephrectomy. For elderly patients with concomitant medical comorbidities the decision to do radical nephrectomy, may worsen pre-existing CKD and accelerate mortality from other conditions including ischaemic heart disease. This latter scenario may have medical consequences more threatening than the renal tumour itself and provide a strong basis for partial nephrectomy to preserve remaining kidney volume more than 144 cc or even active surveillance of smaller renal tumours. This is especially if we can potentially determine from biopsy the grade and metabolic signatures of the cancer.

With good surgical clearance, localised kidney cancer has a low recurrence rate and patients with decreased nephron mass (after partial or radical nephrectomy) rely on careful management of their post-surgical renal function by their primary health care physicians or in more severe CKD stages, by their renal physicians. These patients can be identified pre op if their baseline renal function is less than 83 cc ml/s/1.73m2. Post surgery, patients’ renal function follow-up include renal panel, eGFR evaluation, proteinuria (by albumin or protein creatinine ratio), blood pressure and lipid panel assessment.

References:

1 American Cancer Society website. Available at: http://www.cancer.org/cancer/kidneycancer/detailedguide/kidney-cancer-adult-key-statistics

2 Seow A, Koh WP, Chia KS, Shi LM, Lee HP, Shanmugaratnam K. Trends in Cancer Incidence in Singapore 1968 – 2002. Singapore Cancer Registry. 2006;Report No. 6.

3 Medical Grapevine website. Available at: http://www.medicalgrapevineasia.com/mg/2013/04/22/renal-cell-carcinoma-multimodal-management-for-advanced-disease/

4 Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. NEnglJMed. 2004;351(13):1296-305.

5 Wu FM, Tay MH, Chen Z, Tai BC, Tan LG, Raman L, et al. Postoperative risk of chronic kidney disease in radical nephrectomy and donor nephrectomy patients: a comparison and analysis of predictive factors. Can J Urol. 2014;21(4):7351-7.

6 Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Rising incidence of small renal masses: a need to reassess treatment effect. J Natl Cancer Inst. 2006;98(18):1331-4.

7 Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK. Five-year survival after surgical treatment for kidney cancer: a population-based competing risk analysis. Cancer. 2007;109(9):1763-8.

8 Wu FM, Tay MH, Tai BC, Chen Z, Tan L, Goh BY, et al. Preoperative Renal Volume: A Surrogate Measure for Radical Nephrectomy-Induced Chronic Kidney Disease. J Endourol. 2015;29(12):1406-11.

9 Chen KW, Wu MW, Chen Z, Tai BC, Goh YS, Lata R, et al. Compensatory Hypertrophy After Living Donor Nephrectomy. Transplant Proc. 2016;48(3):716-9.

10 YouTube video. Available at: https://www.youtube.com/watch?v=f_55HTDQbto&feature=youtu.be

11 NCIS Annual Research Meeting (NCAM) website. Available at: httpshttp://ncam.sg/2015/751-2/

12 Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, et al. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol. 2011;59(4):

543-52.

13 Tay MH, Thamboo TP, Wu FM, Zhaojin C, Choo TB, Ramaan L, et al. High R.E.N.A.L. Nephrometry scores are associated with pathologic upstaging of clinical T1 renal-cell carcinomas in radical nephrectomy specimens: implications for nephron-sparing surgery. J Endourol. 2014;28(9):1138-42.

14 Lim HY, Yip YM, Chiong E, Tiong HY, Halliwell B, Esuvaranathan K, et al. Metabolic signatures of renal cell carcinoma. Biochemical and Biophysical Research Communications. 2015;460(4):938-43.

author
Dr Tiong Ho Yee is a senior consultant at the Division of Surgical Oncology (Urology), National University Cancer Institute, Singapore (NCIS). Dr Tiong aims to consistently lead in the field of kidney cancer surgery by performing minimally invasive kidney sparing surgery for small cancers, as well as major open curative operations for large kidney cancers and transplantations. In 2009, he was certified and became full member of the American Society of Transplant Surgeons. He is a certified transplant surgeon by the Ministry of Health, Singapore and serves on its advisory committee for transplantation. He currently is licensed to practice in Singapore, Malaysia, United Kingdom and State of Ohio, United States. With research and dedication, Dr. Tiong believes in delivering patient-centric care and holistic management of his cancer and transplant patients.
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