European Urology

4. Discussion

Ideally, an effective surveillance protocol following curative cancer treatment should detect recurrence in asymptomatic patients during early disease stages, when treatment options can be delivered to achieve longer survival with lower morbidity compared to symptomatic cases. Follow-up can also identify and manage complications related to the initial treatment or tumour recurrence and provide reassurance and guidance to patients [13] x M. Brada. Is there a need to follow-up cancer patients?. Eur J Cancer. 1995;31A:655-657 Crossref. . These considerations hold particularly true for patients with invasive bladder TCC after RC because of the aggressive nature of their disease.

The need for and the duration, intensity, and impact on long-term survival of regular surveillance have been evaluated for several malignancies 14 x K.S. Virgo, A.M. Vernava, W.E. Longo, L.W. McKirgan, F.E. Johnson. Cost of patient follow-up after potentially curative colorectal cancer treatment. JAMA. 1995;273:1837-1841 Crossref. , 15 x M. Jeffery, B.E. Hickey, P.N. Hider. Follow-up strategies for patients treated for non-metastatic colorectal cancer. Cochrane Database Syst Rev. 2007;1:CD002200 , 16 x M.P. Rojas, E. Telaro, A. Russo, et al. Follow-up strategies for women treated for early breast cancer. Cochrane Database Syst Rev. 2005;1:CD001768 , 17 x M. Fung-Kee-Fung, J. Dodge, L. Elit, H. Lukka, A. Chambers, T. Oliver, Cancer Care Ontario Program in Evidence-based Care Gynecology Cancer Disease Site Group. Follow-up after primary therapy for endometrial cancer: a systematic review. Gynecol Oncol. 2006;101:520-529 Crossref. , 18 x R.N. Younes, J.L. Gross, D. Deheinzelin. Follow-up in lung cancer: how often and for what purpose?. Chest. 1999;115:1494-1499 Crossref. , and 19 x S.C. Ritoe, F. de Vegt, I.M. Scheike, et al. Effect of routine follow-up after treatment for laryngeal cancer on life expectancy and mortality: results of a Markov model analysis. Cancer. 2007;109:239-247 Crossref. . Most studies found no survival benefit for regular versus no/nonregular follow-up.

The effect of the various investigations used to diagnose recurrence in postcystectomy patients on long-term oncologic outcome is largely unknown. In our series, the mode of recurrence diagnosis had a statistically significant, albeit small, effect on survival. Patients in whom recurrences were diagnosed by routine follow-up investigations had a slightly higher survival probability than those with symptomatic recurrences. This finding was maintained in a post hoc analysis, excluding patients with secondary urothelial tumours, which could reflect de novo primary tumours rather than true recurrences (data not shown).

Our results contrast with those of the only other study on the issue [20] x B.G. Volkmer, R. Kuefer, G.C. Bartsch Jr., K. Gust, R.E. Hautmann. Oncological followup after radical cystectomy for bladder cancer—is there any benefit?. J Urol. 2009;181:1587-1593 Crossref. , which reported no survival benefit for asymptomatic versus symptomatic recurrence in 444 patients followed for approximately 6 yr after RC. Differences in patient inclusion criteria, patient characteristics, follow-up scheme, and pattern of recurrences may account for this discrepancy. In our series, the pattern of recurrences may explain why the outcome of patients with recurrences diagnosed by routine follow-up is somewhat better than that of symptomatic recurrent patients. Lung metastases and secondary urothelial tumours were usually detected at routine follow-up, while bone metastases and concomitant pelvic and distant recurrences (often the result of bone lesions) were predominantly symptomatic. Indeed, soft tissue metastases respond better to chemotherapy than bone metastases [21] x F. Calabrò, C.N. Sternberg. State-of-the-art management of metastatic disease at initial presentation or recurrence. World J Urol. 2006;24:543-556 . Moreover, most urethral recurrences were diagnosed by routine barbotage cytology, and most were noninvasive. We have previously shown what we confirm herein, namely, that low-stage urethral recurrences durably respond to conservative treatment with endourethral BCG perfusion in >80% of patients, averting the need for urethrectomy with consequent sacrifice of the bladder substitute [22] x C. Varol, G.N. Thalmann, F.C. Burkhard, U.E. Studer. Treatment of urethral recurrence following radical cystectomy and ileal bladder substitution. J Urol. 2004;172:937-942 Crossref. . Whether this good outcome reflects the efficacy of treatment or a rather benign natural history of disease remains unknown.

Besides the potential oncologic value of routine follow-up, it is mandatory for patients with any form of urinary diversion, especially for those receiving orthotopic bladder substitution [23] x R.E. Hautmann, H. Abol-Enein, K. Hafez, et al. Urinary diversion. Urology. 2007;69(Suppl 1):17-49 Crossref. . We previously showed that meticulous surveillance promotes excellent long-term functional results (high urinary continence rate, optimal voiding pattern, preservation of upper urinary tract function, no irreversible metabolic derangements) 24 x U.E. Studer, F.C. Burkhard, M. Schumacher, et al. Twenty years experience with an ileal orthotopic low pressure bladder substitute—lessons to be learned. J Urol. 2006;176:161-166 Crossref. , and 25 x R.E. Hautmann, B.G. Volkmer, M.C. Schumacher, J.E. Gschwend, U.E. Studer. Long-term results of standard procedures in urology: the ileal neobladder. World J Urol. 2006;24:305-314 Crossref. .

Finally, our routine follow-up protocol entailed no serious recurrence-related complications. Patients may also have benefited from the regular psychological support provided by physicians and nurses during follow-up visits.

Our study is not without limitations. First, to fully assess the value of oncologic surveillance, a randomised comparison between patients participating in versus patients not participating in a regular follow-up protocol should be conducted. Such a comparison would, however, raise ethical concerns, because half of the patients in such a study would be excluded from follow-up without robust evidence that surveillance is ineffective. In our series, all patients with symptomatic recurrences had previously been regularly monitored and thus may also have profited from previous follow-up investigations. A substantial survival benefit cannot be expected, as there was not much time between the consultations to develop major tumour progression or severe recurrence-related complications.

Second, our analysis was restricted to patients receiving ileal orthotopic bladder substitution. The rate and pattern of recurrences may be somewhat different for subjects undergoing other forms of urinary diversion because of patient selection, more advanced disease, or less stringent follow-up. Thus, our findings may not apply to all cystectomy patients.

Third, our follow-up scheme may not have been optimal. A higher diagnostic yield and better survival could perhaps be achieved by intensifying CT exams, anticipating bone scans, replacing chest x-ray with CT scans and IVU with CT urography. The possible advantages of these alternatives must be weighed against their higher costs and radiation-induced toxicity [26] x D.J. Brenner, E.J. Hall. Computed tomography—an increasing source of radiation exposure. N Engl J Med. 2007;357:2277-2284 Crossref. . Moreover, considering the sites and timing of the recurrences in our patients, follow-up investigations should be rather frequent in the early postoperative period. This led us to introduce some modifications to our current follow-up scheme (Table 5). However, its usefulness remains to be proven because long-term cancer control rates are comparable across contemporary cystectomy series of major institutions applying various surveillance protocols, and we too have been unable to achieve better outcome with the more recent risk-oriented protocol than with the original one (data not shown). Finally, whether urine cytology after forced diuresis is a valid alternative to IVU or CT scan is still unknown, warranting prospective comparative studies [27] x C. Meissner, G. Giannarini, M.C. Schumacher, H. Thoeny, U.E. Studer, F.C. Burkhard. The efficiency of excretory urography to detect upper urinary tract tumors after cystectomy for urothelial cancer. J Urol. 2007;178:2287-2290 Crossref. .

Our data suggest that urethral barbotage cytology and imaging exams to detect soft tissue metastases are the most useful investigations to be included in a follow-up protocol after RC and ileal orthotopic bladder substitution.