Risk factors and negative consequences of patient’s delay for penile carcinoma

Today, nearly 80 % of patients with penile carcinoma (PC) can be cured [1]. As more patients achieve long-term survival, sexual dysfunction, poor cosmetic appearance, and disability of upright urination are increasingly recognized as negative consequences that severely affect the quality of life and psychosocial well-being. Although various penis-sparing techniques have been successfully developed to replace devastating amputation as the standard treatment of superficial PC (stages Tis, Ta, and T1a), partial amputation or total penectomy with perineal urethrostomy is still the unique strategy for patients of stages T1b–T4 to acquire a curative result [1, 2]. Therefore, treatment at an early stage of disease is the key for patients to acquire acceptable functional and cosmetic outcomes. Unfortunately, delayed first medical consultation (patient’s delay) is quite common in cases of PC. A prospective study [3] and a retrospective study [4] in Sweden respectively exhibited 65 and 37 % of PC patients in a delay of more than 6 months. The reasons behind this considerable ratio remain largely unclear and might involve multiple sociodemographic and psychological factors as well as aspecific initial symptoms [3, 4].

PC is rare in Europe with an incidence of 0.1 to 0.9/100,000 men [5], but it is still a challenge for the developing world. The incidence reaches 8.3/100,000 in Brazil and even higher in Uganda [1, 6]. The higher morbidity makes independent studies in developing countries, focusing on clarifying the phenomenon of patient’s delay, become more urgent because of the great sociodemographic diversity between developing and developed countries. In addition, few studies have investigated the exact impacts of delay on tumor size and stage, treatment strategies, postoperative sexual potency, and prognosis. Whether and to what extent longer delays lead to poorer clinical consequences remain unknown. Under this background, we conducted this multicenter study in China to obtain statistical evidence about these issues for finally promoting patients to improve the ratio of early medical consultation.

In the field of oncology, second best to prevention is early diagnosis and treatment. Patients treated at an early stage of malignant diseases commonly have better quality of life and longer survival [10, 11]. However, potential psychosocial factors and obscure initial symptoms can severely impede early clinical presentation of PC. After preliminary identification by univariate analyses, a multivariate model finally ascertained 4 risk factors (single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms) and 1 protective factor (medical history of condyloma) significantly associated with patient’s delay. Not surprisingly, the role of a partner was important in encouraging patients to timely seek treatment, which even could not be replaced by adult children. PC is a special disease that occurs in male private parts, so only their partners seem to be the optimal consulters before first medical consultation. Even facing medical practitioners, still 23.2 % of delayed patients in this study reported “Feel embarrassed” as the primary reason for their delay, which also partly explains why annual medical exam helps little to decrease the ratio of patient’s delay.

Another main reason causing the delay is aspecific initial symptoms of PC such as erythema, eczema, or induration, which easily mislead patients to think that their symptoms are not serious and will spontaneously resolve. Our investigation even discovered that good education, convenient Internet access, or warning from cancer family history contributed little for eliminating these cognitive barriers. Therefore, improving patient education on initial symptoms of PC is necessary in Chinese men of >40 years old, especially those living in rural area or with heavy drinking habit.

The most interesting and surprising finding in this study is that the medical history of condyloma was a significant protective factor for patient’s delay. However, it is well-known that a history of condyloma is associated with a 3–5-fold increased risk of PC [1, 12]. Three reasons may interpret this unexpected phenomenon: (1) Patients with a history of condyloma have more opportunities to obtain information about PC; (2) mistakenly regarding initial lesions of PC as the recurrence of previous condyloma instead of other inessential benign diseases contributes to timely treatment seeking; (3) the previous experience of curing condyloma helps patients overcome the influence of adverse psychological factors such as “Feel embarrassed or fear”. Moreover, phimosis and smoking are also risk factors of PC [1, 13], but none of them were found significantly associated with patient’s delay.

In addition, 24.4 % of enrollees in this cohort delayed treatment seeking for >6 months, which was much lower than that in two Swedish studies [3, 4]. We supposed that it should be attributed to the extremely low expenses for outpatient consultation (usually <2 dollars/visit) in most areas of China based on the following two facts. One was confirmed by univariate analyses that low family income and lack of medical insurance were not the significant risk factors for delay; the other was that only 8.1 % of delayed patients reported “Feel a lack of financial support” as a primary reason. Becker found that financial concerns stopped uninsured people from seeking care unless they had severe pain or believed that they would die [14]. Therefore, reducing the charge for first medical consultation might contribute to improving the ratio of early clinical presentation of PC, which even can be extrapolated to the whole field of oncology.

Another main finding of this study is that delay >3 months will lead to significantly higher risks for large lesion size and advanced TNM classification. These adverse clinical characteristics significantly decrease the rate of organ sparing under the premise of oncologic cure. However, competent performance for sexual intercourse is extremely important for males [15]. Partial or total amputation inevitably leads to a devastating effect on penile appearance and function, followed by strong impacts on patient’s psychosexual and psychosocial well-being [16, 17]. Penis-sparing techniques obviously allow a better quality of life than amputation but only applicable for superficial PC [1]. Therefore, to minimize patient’s delay is the key of resuming superior sexual function.

Somewhat surprising is that patient’s delay did not impact on postoperative relapses and 5-year OS, and only patients with delay >6 months showed significantly inferior 2-year OS. It can be interpreted by the following three facts: (1) Amputation surgeries offer excellent oncologic control for patients with stage T1b–T3 [16, 18]; (2) nearly 100 % of distant recurrences, which can cause death, occur during the first 2 years of follow-up [19]; (3) patients with delay >6 months have a significant risk of metastasis in our cohort.

This current study has some limitations. First, the time span of delay is impossible to be exactly self-reported by patients, and the investigation was inevitably hampered by recall bias as well as patient’s perception. However, we believe that the bias does not likely play a significant role because the consistency of data between patients reporting and their medical records has been checked carefully. Second, patient’s delay is not the unique delay affecting patient’s prognosis and functional restoration. Doctor’s delay, defined as time span from first medical consultation to the beginning of correct treatment based on accurate diagnosis, also strongly impacts on the clinical consequences [20]. Therefore, a further study focusing on delay after first medical presentation is warranted.

Single, living in rural areas, heavy drinking alcohol, and aspecific initial symptoms are significant risk factors of PC associated with patient’s delay. Delay >3 months may lead to significant risks for adverse clinical characteristics, low penis-sparing rate, and poor sexual function restoration. Although patient’s delay did not impact on postoperative relapses, delay >6 months may have significantly inferior 2-year OS. Minimizing patient’s delay is the key to avoid amputation and resume superior sexual potency; thus, improving patient education on initial symptoms of PC is necessary in men of >40 years old.