Cancer Treatment

Cryoablation of kidney cancer

Standard approach to kidney cancers is surgical resection, usually a complete nephrectomy, althoguh partial nephrectomies are sometimes done when sparing renal function is imperative. Small renal masses have recently been treated by cryoablation (freezing to at least -19.4 °C using liquid nitrogen or argon). Subsequent MRI or CT scans are used to evaluate the ablation, with diminution of the tumor in the cryolesion and lack of contrast enhancement considered a favorable result, and increase of the tumor in the cryolesion or interval growth considered signs of inadequate treatment. A percutaneous biopsy, a standard resection, or retreatment with cryoablation can then occur. The mechanism leading to tumor destruction is uncertain and may be a combination of direct cytotoxicity and damage to vascular elements leading to ischemic necrosis. The cryoablation studies carried out to date fail to convince that a potentially malignant renal mass has been eradicated. The uncertain biopsy data before and after ablation, short follow-up, and requirements for lengthy general anesthesia and frequently for laparoscopic surgical intervention, weaken the argument for renal cryoablation as a paradigm shift.

Kaouk JH, Aron M, Rewcastle JC, Gill IS. Cryotherapy: clinical end points and their experimental foundations. Urology 2006;68(1 suppl):38–44.[

Paul Russo Renal cryoablation: a new treatment in need of careful clinical investigation Nature Clinical Practice Oncology (2006) 3, 286-287

Adjuvant chemo for penis cancer

There is no credible medical evidence for adjuvant chemotherapy for penile cancer, whatever the extent of the resection. The mainstay of treatment is sugical removal and inguinal lymphadenectomy. In more advanced cases, induction, preoperative chemotherapy ha sometimes been delivered. There are also a number of reports suggesting that postop chemoradiation may be usedul in cases of positive margins. However, there are no guidelines, consensus statements or randomized studies, in fact no studies, recommending adjuvant chemotherapy.

Sutent and Taxotere for prostate cancer

Metastatic castrate-resistant prostate tumors typically overexpress receptors for vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF), two of the key cell-surface targets for sunitinib, an oral drug that has emerged as a first-line treatment for renal cell carcinoma. It was reasonable to think that sunitinib, with its dual binding to PDGF and VEGF, would improve upon that, Dr. Zurita said.

Preliminary data from an ongoing phase I/II multicenter study of sunitinib in combination with docetaxel and prednisone, the first to evaluate this new drug in the prostate cancer setting, suggest that this is the case, at least for some patients. During the lead-in period, sunitinib showed a curious trivalent effect on PSA levels. Seven patients had a mean PSA decline of 40%, with three of them showing a greater than 50% decrease. In contrast, 12 patients showed a steep mean rise in PSA of 273% followed by a drop during the 2-week rest period. Six others showed steady mean increases of 73% that did not drop back down during the rest period.

The combination of docetaxel and sunitinib produced PSA reductions of greater than 50% below baseline levels in 10 of the 25 patients (40%). Four of the 20 patients (20%) with measurable disease at baseline had a partial tumor response, based on RECIST criteria, and 11 (55%) had stable disease. Five patients progressed during the year-long follow-up period.

Based on the phase I results, the researchers determined that docetaxel 75 mg/m2 plus sunitinib 37.5 mg represented the optimal dose levels for the ongoing phase II portion of the trial. Sunitinib was generally well tolerated at this dose, and did not significantly add to the side-effect burden of docetaxel plus prednisone. The data was presented in 2007, ECCO abstract 4025.

This trial is now continued as a Phase II study. It is "of unproven value" and should be considered experimental.

O. Guérin et al, Supra-additive antitumor effect of sunitinib malate (SU11248, Sutent®) combined with docetaxel. A new therapeutic perspective in hormone refractory prostate cancer Journal of Cancer Research and Clinical Oncology Issue Volume 134, Number 1 / January, 2008 Pages 51-57

nccn.org, prostate cancer

PET for bladder cancer

Conventional PET using FDG is unsuitable for imaging bladder tumors because of its high urinary excretion. However, it is 67% sensitive, 86% specific and 80% accurate in detecting pathologic lymph nodes in patients with bladder cancer, which exceeds both CT and MRI. Although PET scans are being used as part of research projects in bladder cancer, it is not yet certain how valuable they are in helping to manage the care of patients with bladder cancer. According to a recent review article. “PET demonstrates limited utility in diagnosis and staging of bladdr cancer”. I do not consider it medically necessary.

Jafri SZ, Shetty M, Choyke PL, Bluth EI, Bush WH Jr, Casalino DD, Francis IR, Kawashima A, Papanicolaou N, Rosenfield AT, Sandler CM, Segal AJ, Tempany C, Resnick MI, Expert Panel on Urologic Imaging. Pretreatment staging of invasive bladder cancer. [online publication]. Reston (VA):

American

College

of Radiology (ACR); 2005. 8 p. [51 references]

http://www.moffitt.org/moffittapps/ccj/v9n4/pdf/335.pdf

Salvage radiotherapy after prostatectomy for prostate cancer

Approximately 30 000 men annually in the United States will have recurrence of prostate cancer after radical prostatectomy. Initially, for most of these patients the only evidence of recurrent disease is an increasing serum prostate-specific antigen (PSA) level without radiographic or physical evidence of disease. An estimated 65% of these men will develop bone metastases within 10 years in the absence of salvage therapy.2 A rapid PSA doubling time (PSADT), high-grade disease, and a short disease-free interval after radical prostatectomy are prognostic factors associated with the development of metastases in untreated patients with an increasing PSA level.
In contrast with the results of primary radiotherapy for localized prostate cancer,8-9 the reported success rates of salvage radiotherapy range between 10% and 50%, suggesting that the majority of unselected patients with an increasing PSA level have occult metastases and do not benefit from salvage radiotherapy; however, it remains the standard of care after aoccult distant mets have been ruled out. As such, raditoherapy for salvage is medically necessary.

Andrew J. Stephenson, MD; Shahrokh F. Shariat, MD; Michael J. Zelefsky, MD; Michael W. Kattan, PhD; E. Brian Butler, MD; Bin S. Teh, MD; Eric A. Klein, MD; Patrick A. Kupelian, MD; Claus G. Roehrborn, MD; David A. Pistenmaa, MD; Heather D. Pacholke, MD; Stanley L. Liauw, MD; Matthew S. Katz, MD; Steven A. Leibel, MD; Peter T. Scardino, MD; Kevin M. Slawin, MD
Salvage Radiotherapy for Recurrent Prostate Cancer After Radical Prostatectomy
JAMA. 2004;291:1325-1332.

Mitchell S. Anscher Salvage Radiotherapy for Recurrent Prostate Cancer: The Earlier the Better
JAMA. 2004;291(11):1380-1382.

nccn.org, prostate cancer

LOS for TURP

Transurethral resection of prostate (TURP) is among the top 10 surgical conditions that account for hospital admissions. It is a standard of care approach for benigh prostatic hypertorphy. Bed utilization for TURP is an increasing concern in current times. Methods: Trends in TURP were studied using ICD-9-CM coded Victorian hospital morbidity data from public hospitals from 1987/88 to 1994/95. Detailed morbidity data from the same source for the financial year 1995/96 were used to study predictors of LOS by logistic regression. Results: Length of stay decreased significantly between 1987 and 1995 from 10.6 to 6.1 days. The strongest predictor of increased LOS was admission through the emergency room (odds ratio (OR) 14.7; 95% confidence interval (CI) 11.8–18.3). Other significant predictors were older age, lower socio-economic status, presence of comorbid conditions, occurrence of procedural morbidity, and hospital type and location. More recent data suggests that LOS around the country is now about 3.5 days. There is data suggesting that early removal of the Foley can farther reduce the length of stay ithout increased mobidity. When this is done LOS can be reduced to as littel as two days postop; however, while implemented in many hopsitals in the UK, this ahs not been widely accepted in the USA. The LS of 4 days falls within the usual range in the USA.

E.J Mueller MD, Private Practice, E.J Zeidman MD, Private Practice, P.M Desmond MD [Deceased], I.M Thompson MD, Chief, Department of Surgery, S.A Optenberg Dr. PH, Senior Stastician, J Wasson MD, Professor (1996)  Reduction of length of stay and cost of transurethral resection of the prostate by early catheter removal  BJU International 78 (6), 893–896.

http://www.innovationinurology.nhs.uk/pathways/prostate/follow_up/wolverhampton/case_study.htm

Epirubicin for intravesicular therapy

The anthracycline epirubicin has been investigated for intravesical use in patients with superficial bladder cancer. In multicentre, randomised trials, prophylaxis with intravesical epirubicin 30 to 80mg after transurethral resection (TUR) was more effective than no prophylaxis in the prevention of disease recurrence. Intravesical prophylaxis with epirubicin was as effective as that with equivalent dosages of doxorubicin after TUR. Data are conflicting concerning the relative efficacy of intravesical epirubicin and bacillus Calmette-Guerin (BCG) in patients at intermediate risk of recurrence after TUR, but epirubicin was less effective than BCG in those at high risk. The efficacy and tolerability of prophylaxis with epirubicin relative to that with mitomycin is not yet established. The efficacy of epirubicin as prophylaxis after TUR in combination with BCG or interferon--2b, or as treatment in patients with superficial bladder cancer has been evaluated in small, noncomparative trials, but requires clarification.

Intravesical epirubicin has shown efficacy in preventing disease recurrence after TUR of superficial bladder cancer. In comparison with equivalent dosages of doxorubicin, the efficacy of epirubicin for this indication is generally similar, and the tolerability profile may be more favourable. Epirubicin is less effective than BCG as intravesical prophylaxis in patients at high risk of recurrence after TUR but for patients who can't tolerate BCG,  it is a resonable option. The BC policy does not address such a situation.

Onrust S.V.1; Wiseman L.R.1; Goa K.L.1Epirubicin: A Review of its Intravesical Use in Superficial Bladder Cancer  Drugs & Aging, Volume 15, Number 4, 1 October 1999 , pp. 307-333(27)

MVAC for bladder cancer

Systemic chemotherapy is the only modality that has been shown in phase 3 trials to improve survival in responding patients with advanced bladder cancer).The M-VAC regimen, first reported in 1985 by investigators from Memorial Sloan-Kettering Cancer Center, revealed that urothelial carcinoma was sensitive to chemotherapy. Patients with measurable lesions were found to have a remarkably high response rate of 72%, and 36% attained complete response. Long-term survival was achieved in patients who attained complete response. In addition, patients who achieved a complete response with the combination of chemotherapy and surgery had twice the survival of patients who had only a partial response to chemotherapy and no further surgery (level 3). The median overall survival time for the whole group was 13.1 months. Chemotherapy was more effective in patients with nodal disease only compared with patients who had visceral metastases.

In an update of these results, a retrospective analysis of 5 different M-VAC trials encompassing 203 patients from Memorial Sloan-Kettering Cancer Center was reported. Among 194 evaluable patients, 46 patients achieved a complete response (24%) and 84 patients a partial response (43%), yielding an overall response rate of 67%. The median survival time for all 203 patients was 14.8 months, with a 5-year survival rate of 17% (level 3). The 5-year survival rate for the 46 patients with a complete response after chemotherapy alone was 40%. An additional 30 patients achieved complete response after chemotherapy followed by surgery, with a 5-year survival rate of 33%.Similar results apply in the treatment of metastatic disease.

In the Memorial Sloan-Kettering Cancer Center experience, M-VAC has been associated with severe toxicity and long-term survival in only 15% of patients with visceral metastases and in 30% of patients with nodal disease. The need for improved efficacy and reduced toxicity has led investigators to continue to seek less toxic and more effective regimens. A number of such regimens have been tried. Although CM, CMV, and M-VAC have never been compared in randomized studies, most centers have considered M-VAC to be the standard regimen.

Von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol 2000;18:3068-3077

NCCN.ORG, Bladder cancer

C. Sternberg, S. Donat, J. Bellmunt, R. Millikan, W. Stadler, P. De Mulder, A. Sherif, H. von der Maase, T. Tsukamoto, M. Soloway, Chemotherapy for Bladder Cancer: Treatment Guidelines for Neoadjuvant Chemotherapy, Bladder Preservation, Adjuvant Chemotherapy, and Metastatic Cancer. 
Urology, Volume 69, Issue 1, Pages 62-79, 2007

Gemcitabine carboplatin for bladder cancer

The standard treatment for advanced bladder cancer is the chemotherapy combination consisting of cisplatin (Platinol®), methotrexate, Velban® (vinblastine) and doxorubicin (Adriamycin®), referred to as M-VAC. However, M-VAC is associated with side effects and are particularly difficult to tolerate for patients who have impaired renal function and/or are elderly. Researchers have been evaluating different chemotherapy combinations for the treatment of advanced bladder cancer in patients who are not able to tolerate M-VAC. A randomized study shwoed that gemcitabine/cisplatin is as effective and much less toxic. In an attempt to fartehr reduce toxicity, carboplatin has been substituted for cisplatin. That the two drugs are very similar and carboplatin has been able to substitute for cisplatin in many tumor types. Many such phase II trials have been performed. Since equivalency to cisplatin has been established no phase III trials will be performed.

Nogué-Aliguer M, Carles J, Arrivi A, et al. Gemcitabine and carboplatin in advanced transitional cell carcinoma of the urinary tract.An alternative therapy. Cancer 2003;97:2180-2186.

Bamias A, Moulopoulos LA, Koutras A, Aravantinos G, Fountzilas G, Pectasides D, Kastritis E, Gika D, Skarlos D, Linardou H, Kalofonos HP, Dimopoulos MA.The combination of gemcitabine and carboplatin as first-line treatment in patients with advanced urothelial carcinoma. A Phase II study of the Hellenic Cooperative Oncology Group.
Cancer. 2006 Jan 15;106(2):297-303.

Petrioli R, Frediani B, Manganelli A, Barbanti G, De Capua B, De Lauretis A, Salvestrini F, Mondillo S, Francini G.Comparison between a cisplatin-containing regimen and a carboplatin-containing regimen for recurrent or metastatic bladder cancer patients. A randomized phase II Cancer. 1996 Jan 15;77(2):344-51.

Neoadjuvant chemo for bladder cancer

Randomized clinical trials of neo-adjuvant cisplatin-based combination chemotherapy for locally advanced muscle invasive bladder cancer has shown a survival benefit over cystectomy alone. Pathologic complete response (pT0) after neo-adjuvant chemotherapy is emerging as a potentially important surrogate clinical end point.

The advantages of neo-adjuvant chemotherapy over an adjuvant design include: (1) better tolerance of chemotherapy prior to cystectomy than post-operatively; (2) avoidance of delay in administering chemotherapy due to post-operative morbidity and recuperation often encountered in the adjuvant approach; (3) urinary diversion after radical cystectomy may be associated with some decrement in renal function, thus limiting the use of adjuvant cisplatin, one of the most active agents in bladder cancer. Furthermore, neo-adjuvant chemotherapy allows individual assessment of in vivo tumor response, which can be a guide to future chemotherapy agent selection. Also, downstaging allows for better resectability, and in some selected patients, bladder conservation . The main disadvantage of neo-adjuvant chemotherapy is that definitive local therapy (cystectomy or radiotherapy) is delayed during the treatment period. Furthermore, significant toxicity associated with neo-adjuvant chemotherapy may preclude potentially curative definitive local therapy. In addition, given that neo-adjuvant therapy relies on clinical (rather than pathologic) staging, some low-stage, low-risk patients may unnecessarily receive chemotherapy.

Vale C and Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. (2003) Neo adjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. The Lancet 361:1927–1934.

Winquist E, Kirchner TS, Segal R, et al. (2004) Neo-adjuvant chemotherapy for transitional cell carcinoma of the bladder: a systematic review and meta-analysis. J Urol 171:561–569 (2 Pt 1).

Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. (2005) Neo-adjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data. Eur Urol 48:202–205

R Sawhney et al, Neo-adjuvant chemotherapy for muscle-invasive bladder cancer: a look ahead Annals of Oncology 2006 17(9):1360-1369;