Libni Eapen, MD
In the decades’ long debate around the feasibility, efficacy and desirability of attempting organ preservation versus extirpative cystectomy, there has been a relative paucity of attention directed towards the exact locoregional tumor eradication rate following surgery. Rather, this argument about surgery versus organ preservation has distracted the uro-oncology community from critically examining and addressing this important matter. Pelvic tumor recurrence following contemporary cystectomy has traditionally been considered a relatively infrequent event. Cagiannos and Morash1
compiled 8 institutional series published between 1977 and 2006 reporting local recurrence rates ranging from 3.9% to 29%. These series may have underestimated the true risk of pelvic relapse for patients with locally advanced disease for a variety of reasons including: excluding failures when observed co-synchronously with distant metastases or when there was no biopsy confirmation, using simple numerator/denominator crude risk calculations rather than cumulative incidence rates that account for loss of follow-up and competing risks, or aggregating risk assessments across low and high-risk cohorts.
More recent assessments of pelvic failure risks have suggested the rates are higher than previously assumed. Herr et al,2
reporting the surgical parameters in the neoadjuvant chemotherapy SWOG 8710 trial, demonstrated that despite requiring biopsy confirmation, the crude risk of developing local recurrence following cystectomy in pT3/4 disease was 32%. The 2011 update of the MRC neoadjuvant chemotherapy– cystectomy trial (International Collaboration of Trialists) reported a 48% and 49% rate of pelvic recurrence with and without neoadjuvant chemotherapy, respectively. In a 2011 Canadian survey of contemporary cystectomy, comparably high 48% to 50% cumulative incidence rates of pelvic failure were found.3
As neither neoadjuvant nor adjuvant chemotherapy reduce pelvic failure, locoregional control currently is pursued by optimizing nodal dissection. The well-characterized University of Southern California (USC) experience together with the Memorial Sloan Kettering Cancer Center (MSKCC) and SWOG 8710 reports emphasize the importance of thorough node dissections defined as a minimum of 10-12 nodes. In a 2012 reanalysis of the USC experience following adequate dissection and counting all pelvic failures except those that occur subsequent to the diagnosis of distant metastases, there is a 24% pelvic recurrence rate (Daneshmand, MD, oral communication). In 2014, Christodouleas4
reported the University of Pennsylvania and SWOG 8710 pelvic recurrence experience and identified low, intermediate, and high risk groups according to stage, extent of node dissection, and margin status. These risk groups experienced 8%, 20%, and 41% pelvic recurrence rates at 5 years, respectively.
In aggregate, to date, these clinical data emphasize the neglected problem of significant pelvic failure in pT3/4 patients following cystectomy. In the entire arena of locally advanced solid tumor management—except for bladder cancer—clinical experience and formal experimentation have established multimodality treatment involving varying combinations of surgery, radiotherapy, and systemic treatments to be pivotal in securing optimal cure rates and symptom control. The exhaustive list includes melanomatous and non-melanomatous skin cancer, sarcomas, CNS tumors, head and neck cancers, thyroid cancers, breast, lung, esophagus, gastric, pancreatic, rectal, anorectal, endometrial, cervix, vulvovaginal, and prostate cancers. It is possible that the nexus of under enumeration of pelvic relapse, contention that pelvic recurrence is trumped out of clinical relevance by distant metastases, and concern about the toxicity of integrating cystectomy with adjuvant radiotherapy has created a reluctance to study this approach in the uro-oncologic community, save for in Egypt.